CHAPTER 43
is produced by myocytes of the atria; BNP is produced by
myocytes of the ventricles (and to a lesser extent by cells in
the brain, where BNP was discovered); and CNP is produced
by cells of the vascular endothelium. When blood volume is
excessive, all three peptides are released. (Release of ANP
and BNP is triggered by stretching of the atria and ventricles,
which occurs because of increased preload.)
ANP and BNP have similar actions. Both peptides reduce
blood volume and increase venous capacitance, and thereby
reduce cardiac preload. Three processes are involved. First,
ANP and BNP shift fluid from the vascular system to the
Review of Hemodynamics
extravascular compartment; the underlying mechanism is
increased vascular permeability. Second, these peptides act on
the kidney to cause diuresis (loss of water) and natriuresis
(loss of sodium). Third, they promote dilation of arterioles
and veins, in part by suppressing sympathetic outflow from
the central nervous system. In addition to these actions, ANP
and BNP help protect the heart during the early phase of heart
failure by suppressing both the RAAS and sympathetic outflow,
and by inhibiting proliferation of myocytes. Although CNP
shares some actions of ANP and BNP, its primary action is to
promote vasodilation.
KEY POINTS
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Arterioles serve as control valves to regulate local blood
flow.
Veins are a reservoir for blood.
Arteries are not very distensible. As a result, large increases
in arterial pressure (AP) cause only small increases in
arterial diameter.
Veins are highly distensible. As a result, small increases in
venous pressure cause large increases in venous diameter.
The adult circulatory system contains 5 L of blood, 64%
of which is in systemic veins.
Vasodilation reduces resistance to blood flow, whereas
vasoconstriction increases resistance to flow.
In addition to the small pressure head in venules, three
mechanisms help ensure venous return to the heart: (1)
negative pressure in the right atrium sucks blood toward
the heart; (2) constriction of veins increases venous pressure
and thereby drives blood toward the heart; and (3) contraction of skeletal muscles, in conjunction with one-way
venous valves, pumps blood toward the heart.
Heart rate is increased by sympathetic nerve impulses and
decreased by parasympathetic impulses.
Stroke volume is determined by myocardial contractility,
cardiac preload, and cardiac afterload.
Preload is defined as the amount of tension (stretch) applied
to a muscle before contraction. In the heart, preload is
determined by the force of venous return.
Afterload is defined as the load against which a muscle
exerts its force. For the heart, afterload is the AP that the
left ventricle must overcome to eject blood.
Cardiac afterload is determined primarily by peripheral
resistance, which in turn is determined by the degree of
constriction in arterioles.
Starling’s law states that the force of ventricular contraction
is proportional to myocardial fiber length. Because of this
relationship, when more blood enters the heart, more is
pumped out. As a result, the healthy heart is able to precisely
match output with venous return.
The most important determinant of venous return is systemic
filling pressure, which can be raised by constricting veins
and increasing blood volume.
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Because cardiac muscle operates under Starling’s law, the
right and left ventricles always pump exactly the same
amount of blood (assuming the heart is healthy). Hence,
balance between the pulmonary and systemic circulations
is maintained.
Arterial pressure is regulated by the ANS, the RAAS, the
kidneys, and natriuretic peptides.
The ANS regulates AP (1) through tonic control of heart
rate and peripheral resistance and (2) through the baroreceptor reflex.
The baroreceptor reflex is useful only for short-term control
of AP. When pressure remains elevated or lowered, the
system resets to the new pressure within 1 to 2 days, and
hence ceases to respond.
Drugs that lower AP trigger the baroreceptor reflex and
thereby cause reflex tachycardia. Hence, the baroreceptor
reflex can temporarily negate efforts to lower AP with
drugs.
The RAAS supports AP by causing (1) constriction of
arterioles and veins and (2) retention of water by the
kidneys. Vasoconstriction is mediated by angiotensin II;
water retention is mediated in part by aldosterone.
The kidneys provide long-term control of blood pressure
by regulating blood volume.
Postural (orthostatic) hypotension is caused by decreased
venous return secondary to pooling of blood in veins, which
can occur when we assume an erect posture.
Drugs that dilate veins intensify and prolong postural hypotension. As with other drugs that reduce AP, venodilators
can trigger the baroreceptor reflex and can thereby cause
reflex tachycardia.
Natriuretic peptides defend the cardiovascular system from
volume overload—primarily by reducing blood volume
and promoting vasodilation.
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481
CHAPTER 44
unknown. Eplerenone undergoes metabolism by CYP3A4, followed by excretion
in the urine (67%) and feces (32%). The elimination half-life is 4 to 6 hours.
Adverse Effects
Eplerenone is generally well tolerated. The incidence of adverse
effects is nearly identical to that of placebo. A few adverse
effects—diarrhea, abdominal pain, cough, fatigue, gynecomastia,
flu-like syndrome—occur slightly (1% to 2%) more often with
eplerenone than with placebo.
Hyperkalemia. The greatest concern is hyperkalemia,
which can occur secondary to potassium retention. Because
of this risk, combined use with potassium supplements, salt
substitutes, or potassium-sparing diuretics (e.g., spironolactone,
triamterene) is contraindicated. Combined use with ACE
inhibitors or ARBs is permissible, but should be done with
caution. Eplerenone is contraindicated for patients with high
serum potassium (above 5.5 mEq/L) and for patients with
impaired renal function or type 2 diabetes with microalbuminuria, both of which can promote hyperkalemia. Monitoring
potassium levels is recommended for patients at risk (e.g.,
those taking ACE inhibitors or ARBs).
Drug Interactions
Inhibitors of CYP3A4 can increase levels of eplerenone, thereby
posing a risk of toxicity. Weak inhibitors (e.g., erythromycin,
saquinavir, verapamil, fluconazole) can double eplerenone
levels. Strong inhibitors (e.g., ketoconazole, itraconazole) can
increase levels fivefold. If eplerenone is combined with a weak
inhibitor, eplerenone dosage should be reduced. Eplerenone
should not be combined with a strong inhibitor.
Drugs Acting on the Renin-Angiotensin-Aldosterone System
Drugs that raise potassium levels can increase the risk of
hyperkalemia. Eplerenone should not be combined with potassium supplements, salt substitutes, or potassium-sparing
diuretics. Combining eplerenone with ACE inhibitors or ARBs
should be done with caution.
Drugs similar to eplerenone (e.g., ACE inhibitors and
diuretics) are known to increase levels of lithium. Although
the combination of eplerenone and lithium has not been studied,
caution is nonetheless advised. Lithium levels should be
measured frequently.
Preparations, Dosage, and Administration
Eplerenone [Inspra] is available in 25- and 50-mg tablets. The usual starting
dosage is 50 mg once a day, taken with or without food. After 4 weeks, dosage
can be increased to 50 mg twice daily (if the hypotensive response has been
inadequate). Raising the dosage above 100 mg/day is not recommended because
doing so is unlikely to increase the therapeutic response, but will increase the
risk of hyperkalemia. In patients taking weak inhibitors of CYP3A4, the initial
dosage should be reduced by 50% (to 25 mg once a day).
Spironolactone
Spironolactone [Aldactone], a much older drug than eplerenone, blocks receptors
for aldosterone, but also binds with receptors for other steroid hormones (e.g.,
glucocorticoids, progesterone, androgens). Blockade of aldosterone receptors
underlies beneficial effects in hypertension and heart failure, as well as the
drug’s major adverse effect: hyperkalemia. Binding with receptors for other
steroid hormones underlies additional adverse effects: gynecomastia, menstrual
irregularities, impotence, hirsutism, and deepening of the voice. The basic
pharmacology of spironolactone and its use in heart failure are discussed in
Chapters 41 and 48, respectively.
KEY POINTS
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The RAAS helps regulate blood pressure, blood volume,
and fluid and electrolyte balance. The system can promote
cardiovascular pathology.
The RAAS acts through production of angiotensin II and
aldosterone.
Angiotensin II has much greater biologic activity than
angiotensin I or angiotensin III.
Angiotensin II is formed by the actions of two enzymes:
renin and ACE.
Angiotensin II causes vasoconstriction (primarily in
arterioles) and release of aldosterone. In addition, angiotensin II can promote pathologic changes in the heart and
blood vessels.
Aldosterone acts on the kidneys to promote retention of
sodium and water. In addition, aldosterone can also mediate
pathologic changes in cardiovascular function.
The RAAS raises blood pressure by causing vasoconstriction
and by increasing blood volume (secondary to aldosteronemediated retention of sodium and water).
In addition to the traditional RAAS, in which angiotensin II
is produced in the blood and then carried to target tissues,
angiotensin II can be produced locally by individual
tissues.
Beneficial effects of ACE inhibitors result largely from
inhibition of ACE and partly from inhibition of kinase II
(the name for ACE when the substrate is bradykinin).
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By inhibiting ACE, ACE inhibitors decrease production
of angiotensin II. The result is vasodilation, decreased
blood volume, and prevention or reversal of pathologic
changes in the heart and blood vessels mediated by
angiotensin II and aldosterone.
ACE inhibitors (and ARBs) are used to treat patients with
hypertension, heart failure, MI, and established diabetic
nephropathy. In addition, they are used to prevent MI,
stroke, and death from cardiovascular causes in patients
at high risk for a cardiovascular event. Of note, ACE
inhibitors (and ARBs) are not effective for primary prevention of diabetic nephropathy.
Preliminary data indicate that ACE inhibitors (and ARBs)
can reduce the risk of developing diabetic retinopathy,
although they can’t slow the progression of established
retinopathy.
ACE inhibitors can produce significant first-dose hypotension by causing a sharp drop in circulating angiotensin II.
Cough, secondary to accumulation of bradykinin, is the
most common reason for discontinuing ACE inhibitors.
By suppressing aldosterone release, ACE inhibitors can
cause hyperkalemia. Exercise caution in patients taking
potassium supplements, salt substitutes, or potassiumsparing diuretics.
ACE inhibitors can cause major fetal malformations
and should be avoided during pregnancy. Until recently,
Continued
493
UNIT VII
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Drugs That Affect the Heart, Blood Vessels, and Blood
we thought that risk was limited to exposure during the
second and third trimesters. However, new data indicate
that exposure during the first trimester may be dangerous
as well.
ACE inhibitors can cause a precipitous drop in blood
pressure in patients with bilateral renal artery stenosis (or
stenosis in the artery to a single remaining kidney).
ARBs block the actions of angiotensin II in blood vessels,
the adrenals, and all other tissues.
ARBs are similar to ACE inhibitors in that they cause
vasodilation, suppress aldosterone release, promote excretion of sodium and water, reduce blood pressure, and cause
birth defects and angioedema.
ARBs differ from ACE inhibitors in that they have a much
lower incidence of hyperkalemia or cough.
Aliskiren, a DRI, binds tightly with renin and thereby
inhibits cleavage of angiotensinogen into angiotensin I.
As a result, the drug suppresses the entire RAAS.
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Like the ACE inhibitors and ARBs, aliskiren causes
vasodilation, suppresses aldosterone release, promotes
excretion of sodium and water, reduces blood pressure,
and causes birth defects and angioedema.
Despite their similarities, aliskiren, ARBs, and ACE inhibitors are not clinically interchangeable.
Aldosterone antagonists (spironolactone, eplerenone) block
receptors for aldosterone.
By blocking aldosterone receptors, aldosterone antagonists
can (1) promote renal excretion of sodium and water (and
can thereby reduce blood volume and blood pressure) and
(2) prevent or reverse pathologic effects of aldosterone on
cardiovascular structure and function.
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Summary of Major Nursing Implicationsa
Identifying High-Risk Patients
ACE inhibitors are contraindicated during the second and
third trimesters of pregnancy and for patients with (1) bilateral
renal artery stenosis (or stenosis in the artery to a single
remaining kidney) or (2) a history of hypersensitivity reactions
(especially angioedema) to ACE inhibitors.
Exercise caution in patients with salt or volume depletion,
renal impairment, or collagen vascular disease, and in those
taking potassium supplements, salt substitutes, potassiumsparing diuretics, ARBs, aliskiren, or lithium.
ANGIOTENSIN-CONVERTING
ENZYME INHIBITORS
Benazepril
Captopril
Enalapril
Enalaprilat
Fosinopril
Lisinopril
Moexipril
Perindopril
Quinapril
Ramipril
Trandolapril
Unless indicated otherwise, the implications summarized in
the sections that follow pertain to all of the ACE inhibitors.
Preadministration Assessment
Therapeutic Goals
ACE inhibitors are used to:
Implementation: Administration
Routes
Oral. All ACE inhibitors (except enalaprilat).
Intravenous. Enalaprilat.
Dosage and Administration
Dosage is low initially and then gradually increased.
Instruct patients to administer captopril and moexipril at
least 1 hour before meals. All other oral ACE inhibitors can
• Reduce blood pressure in patients with hypertension (all
ACE inhibitors).
• Improve hemodynamics in patients with heart failure
(captopril, enalapril, fosinopril, lisinopril, quinapril).
• Slow progression of established diabetic nephropathy
(captopril).
• Reduce mortality following acute MI (lisinopril).
• Treat heart failure after MI (ramipril, trandolapril).
• Reduce the risk of MI, stroke, or death from cardiovascular
causes in patients at high risk (ramipril).
• Reduce cardiovascular mortality or nonfatal MI in patients
with stable coronary artery disease (perindopril).
Baseline Data
Determine blood pressure, and obtain a white blood cell
count and differential.
be administered with food.
Ongoing Evaluation and Interventions
Monitoring Summary
Monitor blood pressure closely for 2 hours after the first dose
and periodically thereafter. Obtain a white blood cell count
and differential every 2 weeks for the first 3 months of therapy
and periodically thereafter.
Evaluating Therapeutic Effects
Hypertension. Monitor for reduced blood pressure. The
usual target pressure is systolic/diastolic of 140/90 mm Hg
or 130/80 in patients with diabetes.
Heart Failure. Monitor for a lessening of signs and
symptoms (e.g., dyspnea, cyanosis, jugular vein distention,
edema).
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CHAPTER 44
Drugs Acting on the Renin-Angiotensin-Aldosterone System
Summary of Major Nursing Implicationsa—cont’d
Diabetic Nephropathy. Monitor for proteinuria and
altered glomerular filtration rate.
Minimizing Adverse Effects
First-Dose Hypotension. Severe hypotension can occur
with the first dose. Minimize hypotension by (1) withdrawing
diuretics 2 to 3 days before initiating ACE inhibitors and (2)
using low initial doses. Monitor blood pressure for 2 hours
following the first dose. Instruct patients to lie down if
hypotension develops. If necessary, infuse normal saline to
restore pressure.
Cough. Warn patients about the possibility of persistent
dry, irritating, nonproductive cough. Instruct them to consult
the prescriber if cough is bothersome. Stopping the ACE
inhibitor may be indicated.
Hyperkalemia. ACE inhibitors may increase potassium
levels. Instruct patients to avoid potassium supplements and
potassium-containing salt substitutes unless they are prescribed by the provider. Potassium-sparing diuretics must
also be avoided.
Fetal Injury. Warn women of childbearing age that taking
ACE inhibitors during the second and third trimesters of
pregnancy can cause major fetal injury (hypotension, hyperkalemia, skull hypoplasia, anuria, reversible and irreversible
renal failure, death) and that taking these drugs earlier in
pregnancy may pose a risk as well. If the patient becomes
pregnant, withdraw ACE inhibitors as soon as possible. Closely
monitor infants who have been exposed to ACE inhibitors
during the second or third trimester for hypotension, oliguria,
and hyperkalemia.
Angioedema. This rare and potentially fatal reaction is
characterized by giant wheals and edema of the tongue, glottis,
and pharynx. Instruct patients to seek immediate medical
attention if these symptoms develop. If angioedema is
diagnosed, ACE inhibitors should be discontinued and never
used again. Treat severe reactions with subcutaneous
epinephrine.
Renal Failure. Renal failure is a risk for patients with
bilateral renal artery stenosis or stenosis in the artery to a
single remaining kidney. ACE inhibitors must be used with
extreme caution in these people.
Neutropenia (Mainly With Captopril). Neutropenia
poses a high risk of infection. Inform patients about early
signs of infection (fever, sore throat, mouth sores), and instruct
them to notify the prescriber if these occur. If neutropenia
develops, withdraw the drug immediately; neutrophil counts
should normalize in approximately 2 weeks. Neutropenia is
most likely in patients with renal impairment and collagen
vascular diseases (e.g., systemic lupus erythematosus,
scleroderma); monitor these patients closely.
Minimizing Adverse Interactions
Diuretics. Diuretics may intensify first-dose hypotension.
Withdraw diuretics 2 to 3 days before beginning an ACE
inhibitor. Diuretics may be resumed later if needed.
Antihypertensive Agents. The antihypertensive effects
of ACE inhibitors are additive with those of other antihypertensive drugs (e.g., ARBs, diuretics, sympatholytics, vasodilators,
calcium channel blockers). When an ACE inhibitor is added
to an antihypertensive regimen, dosages of the other drugs
may require reduction.
Drugs That Elevate Potassium Levels. ACE inhibitors
increase the risk of hyperkalemia associated with potassium
supplements, potassium-sparing diuretics, and possibly
aliskiren. Risk can be minimized by avoiding potassium
supplements and potassium-sparing diuretics except when
they are clearly indicated.
Lithium. ACE inhibitors can increase serum levels of
lithium, causing toxicity. Monitor lithium levels frequently.
Nonsteroidal Anti-Inflammatory Drugs. NSAIDs (e.g.,
aspirin, ibuprofen) can interfere with the antihypertensive
effects of ACE inhibitors. Advise patients to minimize
NSAID use.
ANGIOTENSIN II RECEPTOR BLOCKERS
Azilsartan
Candesartan
Eprosartan
Irbesartan
Losartan
Olmesartan
Telmisartan
Valsartan
Unless indicated otherwise, the implications summarized
here pertain to all of the ARBs.
Preadministration Assessment
Therapeutic Goals
ARBs are used to:
• Reduce blood pressure in patients with hypertension
(all ARBs).
• Treat heart failure (candesartan, valsartan).
• Slow the progression of established diabetic nephropathy
(irbesartan, losartan).
• Prevent stroke in patients with hypertension and LV
hypertrophy (losartan).
• Protect against MI, stroke, and death from cardiovascular
causes in high-risk patients, but only if they can’t tolerate
ACE inhibitors (telmisartan).
• Treat heart failure after MI (valsartan).
Baseline Data
Determine blood pressure.
Identifying High-Risk Patients
ARBs are contraindicated during the second and third trimesters of pregnancy and for patients with either (1) bilateral
renal artery stenosis (or stenosis in the artery to a single
remaining kidney) or (2) a history of hypersensitivity reactions
(especially angioedema) to ARBs.
Implementation: Administration
Route
Oral.
Continued
495
UNIT VII
Drugs That Affect the Heart, Blood Vessels, and Blood
Summary of Major Nursing Implicationsa—cont’d
Dosage and Administration
Inform patients that ARBs may be taken with or without
food.
Ongoing Evaluation and Interventions
Evaluating Therapeutic Effects
Hypertension. Monitor for reduced blood pressure. The
usual target pressure is systolic/diastolic of 140/90 mm Hg
or 130/80 in patients with diabetes.
Heart Failure. Monitor for a lessening of signs and
symptoms (e.g., dyspnea, cyanosis, jugular vein distention,
edema).
Diabetic Nephropathy. Monitor for proteinuria and
altered glomerular filtration rate.
Minimizing Adverse Effects
Angioedema. This rare and potentially fatal reaction
is characterized by giant wheals and edema of the tongue,
glottis, and pharynx. Instruct patients to seek immediate
medical attention if these symptoms develop. If angioedema
is diagnosed, ARBs should be discontinued and never used
again. Treat severe reactions with subcutaneous epinephrine.
Fetal Injury. Warn women of childbearing age that ARBs
can cause fetal injury during the second and third trimesters
of pregnancy, and may pose a risk earlier in pregnancy as
well. If the patient becomes pregnant, withdraw ARBs as
soon as possible. Closely monitor infants who have been
exposed to ARBs during the second or third trimester for
hypotension, oliguria, and hyperkalemia.
Renal Failure. Renal failure is a risk for patients with
bilateral renal artery stenosis or stenosis in the artery to a
single remaining kidney. ARBs are contraindicated for these
people.
Minimizing Adverse Interactions
Antihypertensive Agents. The antihypertensive effects
of ARBs are additive with those of other antihypertensive
drugs (e.g., diuretics, sympatholytics, vasodilators, ACE
inhibitors, calcium channel blockers). When an ARB is added
to an antihypertensive regimen, dosages of the other drugs
may require reduction.
ALISKIREN, A DIRECT RENIN INHIBITOR
Preadministration Assessment
Therapeutic Goal
Reduction of blood pressure in patients with hypertension.
Baseline Data
Determine blood pressure.
Exercise caution in patients taking potassium supplements,
salt substitutes, potassium-sparing diuretics, or ACE inhibitors.
Implementation: Administration
Route
Oral.
Dosage and Administration
Advise patients to take each daily dose at the same time
with respect to meals (e.g., 1 hour before dinner). Dosage
should be low (150 mg/day) initially, and increased to a
maximum of 300 mg/day if needed.
Ongoing Evaluation and Interventions
Minimizing Adverse Effects
Hyperkalemia. Aliskiren may increase potassium levels.
Instruct patients to avoid potassium supplements and
potassium-containing salt substitutes unless they are prescribed by the provider. Potassium-sparing diuretics must
also be avoided. Exercise caution in patients taking an ACE
inhibitor.
Fetal Injury. Warn women of childbearing age that
aliskiren taken during the second and third trimesters of
pregnancy can cause fetal injury (hypotension, hyperkalemia,
skull hypoplasia, anuria, reversible and irreversible renal
failure, death). If the patient becomes pregnant, withdraw
aliskiren as soon as possible. Closely monitor infants who
have been exposed to aliskiren during the second or third
trimester for hypotension, oliguria, and hyperkalemia.
Angioedema. This rare and potentially fatal reaction
is characterized by giant wheals and edema of the tongue,
glottis, and pharynx. Instruct patients to seek immediate
medical attention if these symptoms develop. If angioedema
is diagnosed, aliskiren should be discontinued and never used
again. Treat severe reactions with subcutaneous epinephrine.
Minimizing Adverse Interactions
Drugs That Elevate Potassium Levels. Aliskiren
increases the risk of hyperkalemia associated with ACE
inhibitors, potassium supplements, and potassium-sparing
diuretics. Risk can be minimized by avoiding ACE inhibitors,
potassium supplements, and potassium-sparing diuretics except
when they are clearly indicated.
Antihypertensive Agents. The antihypertensive effects
of aliskiren are additive with those of other antihypertensive
drugs (e.g., ACE inhibitors, ARBs, diuretics, sympatholytics,
vasodilators, calcium channel blockers). When aliskiren is
added to an antihypertensive regimen, dosages of the other
drugs may require reduction.
Identifying High-Risk Patients
Aliskiren is contraindicated during the second and third
trimesters of pregnancy.
Patient education information is highlighted as blue text.
a
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CHAPTER 45
of neurologic injury following rupture of an intracranial aneurysm. Benefits
derive from preventing cerebral arterial spasm that follows subarachnoid
hemorrhage (SAH) and can result in ischemic neurologic injury. Dosing (60 mg
every 4 hours) should begin within 96 hours of SAH and continue for 21 days.
Nimotop
is available in 30-mg liquid-filled capsules for oral administration
and as a 60 mg/20 mL oral solution [Nymalize]. Nimodipine must never be
given intravenously, owing to a risk of potentially fatal cardiovascular events.
Nisoldipine
Like nifedipine, nisoldipine [Sular] produces selective blockade of calcium
channels in blood vessels; the drug has minimal direct effects on the heart.
The only approved indication is hypertension. Nisoldipine is well absorbed
following oral administration, but the first-pass effect limits bioavailability
to 5%. Plasma levels peak 6 hours after administration. The most common
side effects are dizziness, headache, and peripheral edema. Reflex tachycardia
may also occur. As with other CCBs, eczematous rash may develop in older
patients. Nisoldipine is available in ER tablets (8.5, 17, 20, 25.5, 30, 34, and
40 mg). The dosage for hypertension is 17 to 60 mg once a day.
Calcium Channel Blockers
Clevidipine
Clevidipine [Cleviprex] is indicated only for intravenous therapy of severe
hypertension, defined as systolic blood pressure above 180 mm Hg or diastolic
pressure above 110 mm Hg. The drug has an ultrashort half-life (about 1
minute), owing to rapid inactivation by plasma esterases. Effects are not
altered by impairment of liver or kidney function. Because of IV dosing and
rapid inactivation, blood pressure falls quickly and then rises quickly when
the infusion is slowed or stopped. As a result, responses can be easily titrated.
Clevidipine is formulated in a lipid emulsion made from soybean oil and egg
yolk phospholipids, and hence is contraindicated for patients allergic to soybeans
or eggs. Clevidipine is supplied in single-dose vials (50, 100, or 250 mL) at
a concentration of 0.5 mg/mL. For patients with severe hypertension, the
infusion rate is 1 to 2 mg/hr initially, and can be doubled every 90 seconds
up to a maximum of 32 mg/hr. In clinical trials, the average time to reach the
target blood pressure was 10.9 minutes. The most common side effects are
headache, nausea, and vomiting. Like other dihydropyridines, clevidipine can
cause hypotension and reflex tachycardia.
KEY POINTS
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Calcium channels are gated pores in the cytoplasmic
membrane that regulate calcium entry into cells.
In blood vessels, calcium entry causes vasoconstriction,
and hence calcium channel blockade causes vasodilation.
In the heart, calcium entry increases heart rate, AV conduction, and myocardial contractility, so calcium channel
blockade has the opposite effects.
In the heart, calcium channels are coupled to beta1 receptors,
activation of which enhances calcium entry. As a result,
calcium channel blockade and beta blockade have identical
effects on cardiac function.
At therapeutic doses, nifedipine and the other dihydropyridines act primarily on VSM; in contrast, verapamil
and diltiazem act on VSM and on the heart.
All CCBs promote vasodilation, and hence are useful in
hypertension and angina pectoris.
Because they suppress AV conduction, verapamil and
diltiazem are useful for treating cardiac dysrhythmias (in
addition to hypertension and angina pectoris).
Because of their cardiosuppressant effects, verapamil and
diltiazem can cause bradycardia, partial or complete AV
block, and exacerbation of heart failure.
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Beta blockers intensify cardiosuppression caused by
verapamil and diltiazem.
Nifedipine and other dihydropyridines can cause reflex
tachycardia. Tachycardia is most intense with immediaterelease formulations, and much less intense with sustainedrelease formulations.
Beta blockers can be used to suppress reflex tachycardia
caused by nifedipine and other dihydropyridines.
Because they cause vasodilation, all CCBs can cause
dizziness, headache, and peripheral edema.
In toxic doses, nifedipine and other dihydropyridines can
cause cardiosuppression, just like verapamil and diltiazem.
Immediate-release nifedipine has been associated with
increased mortality in patients with myocardial infarction
and unstable angina, although a causal relationship has
not been established. The National Heart, Lung, and Blood
Institute recommends that immediate-release nifedipine,
especially in higher doses, be used with great caution, if
at all.
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Summary of Major Nursing Implicationsa
VERAPAMIL AND DILTIAZEM
Preadministration Assessment
Therapeutic Goal
Verapamil and diltiazem are indicated for hypertension, angina
pectoris, and cardiac dysrhythmias (atrial fibrillation, atrial
flutter, and paroxysmal supraventricular tachycardia).
Baseline Data
For all patients, determine blood pressure and pulse rate,
and obtain laboratory evaluations of liver and kidney function.
For patients with angina pectoris, obtain baseline data on
the frequency and severity of anginal attacks. For baseline
data relevant to hypertension, see Chapter 47.
Identifying High-Risk Patients
Verapamil and diltiazem are contraindicated for patients with
severe hypotension, sick sinus syndrome (in the absence of
electronic pacing), and second-degree or third-degree AV
block. Use with caution in patients with heart failure or liver
impairment and in patients taking digoxin or beta blockers.
Implementation: Administration
Routes
Oral, IV.
Administration
Oral. Verapamil and diltiazem may be used for angina
pectoris and essential hypertension. Verapamil may be used
Continued
503
Summary of Major Nursing Implicationsa—cont’d
with digoxin to control ventricular rate in patients with atrial
fibrillation and atrial flutter.
Extended-release formulations are reserved for essential
hypertension. Instruct patients to swallow extended-release
formulations whole, without crushing or chewing.
Before dosing, measure blood pressure and pulse rate. If
hypotension or bradycardia is detected, withhold medication
and notify the prescriber.
Intravenous. Intravenous therapy with verapamil or
diltiazem is reserved for cardiac dysrhythmias. Perform
injections slowly (over 2 to 3 minutes). Monitor the ECG
for AV block, sudden reduction in heart rate, and prolongation
of the PR or QT interval. Have facilities for cardioversion
and cardiac pacing immediately available.
Ongoing Evaluation and Interventions
Evaluating Therapeutic Effects
Angina Pectoris. Keep an ongoing record of anginal
attacks, noting the time and intensity of each attack and the
likely precipitating event. Teach outpatients to chart the time,
intensity, and circumstances of their attacks, and to notify
the prescriber if attacks increase.
Essential Hypertension. Monitor blood pressure periodically.
For most patients, the goal is to reduce systolic/diastolic pressure
to a value below 140/90 mm Hg. Teach patients to self-monitor
their blood pressure and to maintain a blood pressure record.
Minimizing Adverse Effects
Cardiosuppression. Verapamil and diltiazem can cause
bradycardia, AV block, and heart failure. Inform patients
about manifestations of cardiac effects (e.g., slow heartbeat,
shortness of breath, weight gain) and instruct them to notify
the prescriber if these occur. If cardiac impairment is severe,
drug use should stop.
Peripheral Edema. Inform patients about signs of edema
(swelling in ankles or feet), and instruct them to notify the
prescriber if these occur. If necessary, edema can be reduced
with a diuretic.
Constipation. Constipation occurs primarily with verapamil. Advise patients that constipation can be minimized
by increasing dietary fluid and fiber.
Minimizing Adverse Interactions
Digoxin. The combination of digoxin with verapamil or
diltiazem increases the risk of partial or complete AV block.
Monitor for indications of impaired AV conduction (missed
beats, slowed ventricular rate).
Verapamil (and possibly diltiazem) can increase plasma
levels of digoxin. Digoxin dosage should be reduced.
Beta Blockers. Concurrent use of a beta blocker with verapamil or diltiazem can cause bradycardia, AV block, or heart
failure. Monitor closely for cardiac suppression. Administer
intravenous verapamil and beta blockers several hours apart.
Grapefruit Juice. Grapefruit juice can raise levels of verapamil and diltiazem. Toxicity may result. Advise patients that
it may be prudent to minimize grapefruit juice consumption.
Managing Acute Toxicity
Remove unabsorbed drug with gastric lavage followed by
activated charcoal. Give IV calcium to help counteract excessive vasodilation and reduced myocardial contractility.
To raise blood pressure, give IV norepinephrine. Intravenous fluids and placing the patient in modified Trendelenburg’s
position can also help.
Bradycardia and AV block can be reversed with atropine
and glucagon. If these are inadequate, electronic pacing may
be required.
DIHYDROPYRIDINES
Amlodipine
Clevidipine
Felodipine
Isradipine
Nicardipine
Nifedipine
Nimodipine
Nisoldipine
Preadministration Assessment
Therapeutic Goal
Amlodipine, nifedipine, and nicardipine are approved for
essential hypertension and angina pectoris.
Isradipine, felodipine, and nisoldipine are approved for
hypertension only.
Nimodipine is used only for subarachnoid hemorrhage.
Clevidipine is used only for IV therapy of severe
hypertension.
Baseline Data
See nursing implications for Verapamil and Diltiazem.
Identifying High-Risk Patients
Use dihydropyridines with caution in patients with hypotension, sick sinus syndrome (in the absence of electronic pacing),
angina pectoris (because of reflex tachycardia), heart failure,
and second-degree or third-degree AV block.
Implementation: Administration
Route
Oral. All dihydropyridines except clevidipine.
Intravenous. Nicardipine, clevidipine.
Administration
Instruct patients to swallow sustained-release formulations
whole, without crushing or chewing.
Ongoing Evaluation and Interventions
Evaluating Therapeutic Effects
See nursing implications for Verapamil and Diltiazem.
Minimizing Adverse Effects
Reflex Tachycardia. Reflex tachycardia can be suppressed
with a beta blocker.
Peripheral Edema. Inform patients about signs of edema
and instruct them to notify the prescriber if these occur. If
necessary, edema can be reduced with a diuretic.
Managing Acute Toxicity
Continued
See nursing implications for Verapamil and Diltiazem.
Patient education information is highlighted as blue text.
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CHAPTER 46
Preparations, Dosage, and Administration
Sodium nitroprusside [Nitropress] is available in powdered form (50 mg) to
be dissolved and then diluted for IV infusion. Fresh solutions may have a
faint brown color. Solutions that are deeply colored (blue, green, dark red)
should be discarded. Nitroprusside in solution can be degraded by light, and
hence should be protected with an opaque material.
Blood pressure can be adjusted to practically any level by increasing or
decreasing the rate of infusion. The initial infusion rate is 0.3 mcg/kg/min.
Vasodilators
The maximal rate is 10 mcg/kg/min. If infusion at the maximal rate for 10
minutes fails to produce an adequate drop in blood pressure, administration
should stop. During the infusion, blood pressure should be monitored continuously, with either an arterial line or an electronic monitoring device. No other
drugs should be mixed with the nitroprusside solution.
KEY POINTS
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Some vasodilators are selective for arterioles, some are
selective for veins, and some dilate both types of vessel.
Drugs that dilate arterioles reduce cardiac afterload and
can thereby reduce cardiac work while increasing cardiac
output and tissue perfusion.
Drugs that dilate veins reduce cardiac preload and can
thereby reduce cardiac work, cardiac output, and tissue
perfusion.
Principal indications for vasodilators are essential hypertension, hypertensive crisis, angina pectoris, heart failure, and
myocardial infarction.
Drugs that dilate veins can cause orthostatic hypotension.
Drugs that dilate arterioles or veins can cause reflex
tachycardia, which increases cardiac work and elevates
blood pressure. Reflex tachycardia can be blunted with a
beta blocker.
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Drugs that dilate arterioles or veins can cause fluid retention,
which can be blunted with a diuretic.
Hydralazine causes selective dilation of arterioles.
Hydralazine can cause a syndrome that resembles SLE.
Minoxidil causes selective and profound dilation of
arterioles.
Minoxidil can cause hypertrichosis.
Sodium nitroprusside dilates arterioles and veins.
Prolonged infusion of nitroprusside can result in toxic
accumulation of cyanide and thiocyanate.
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UNIT VII
Drugs That Affect the Heart, Blood Vessels, and Blood
BP is labetalol (20 mg by IV bolus over 2 minutes); dosing
may be repeated at 10-minute intervals up to a total of 300 mg.
Because severe preeclampsia can evolve into eclampsia,
an antiseizure drug may be given for prophylaxis. Magnesium
sulfate is the drug of choice. In one study, prophylaxis with
magnesium sulfate reduced the risk of eclampsia by 58% and
the risk of death by 45%. Dosing is the same as for treating
eclampsia.
If eclampsia develops, magnesium sulfate is the preferred
drug for seizure control. Initial dosing consists of a 4- to 6-gm
IV loading dose followed by 5 gm IM injected into each buttock.
Maintenance consists of continuous IV infusion of 1 to 2 gm/hr
or 5 gm IM injected into alternating buttocks every 4 hours.
To ensure therapeutic effects and prevent toxicity, blood levels
of magnesium, as well as presence of patellar reflex, should
be monitored. The target range for serum magnesium is 4 to
7 mEq/L (the normal range for magnesium is 1.5 to 2 mEq/L).
Can drugs help prevent preeclampsia in those at risk?
Yes. When started before 16 weeks of gestation, low-dose
aspirin reduces risk by about 50%. Similarly, L-arginine (combined with antioxidant vitamins) can also help. By contrast,
several other preparations—magnesium, zinc, vitamin C,
vitamin E, fish oil, and diuretics—appear to offer no protection
at all.
KEY POINTS
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Hypertension is defined as SBP greater than 130 mm Hg
or DBP greater than 80 mm Hg.
Primary hypertension (essential hypertension), defined as
hypertension with no identifiable cause, is the most common
form of hypertension.
Untreated hypertension can lead to heart disease, kidney
disease, and stroke.
In patients older than 50, elevated systolic BP represents
a greater cardiovascular risk than elevated diastolic BP.
The goal of antihypertensive therapy is to decrease morbidity and mortality without decreasing quality of life. For
most patients, this goal is achieved by maintaining BP
between 120/80 and 130/80 mm Hg.
To reduce BP, two types of treatment may be used: drug
therapy and lifestyle modification (smoking cessation,
reduction of salt and alcohol intake, following the DASH
diet, and increasing aerobic exercise).
The baroreceptor reflex, the kidneys, and the RAAS can
oppose our attempts to lower BP with drugs. We can
counteract the baroreceptor reflex with a beta blocker, the
kidneys with a diuretic, and the RAAS with an ACE
inhibitor, ARB, DRI, or aldosterone antagonist.
Thiazide diuretics (e.g., hydrochlorothiazide, chlorthalidone)
and loop diuretics (e.g., furosemide) reduce BP in two
ways: they reduce blood volume (by promoting diuresis)
and they reduce arterial resistance (by an unknown
mechanism).
Loop diuretics should be reserved for (1) patients who
need greater diuresis than can be achieved with thiazides
and (2) patients with a low GFR (because thiazides don’t
work when GFR is low).
Beta blockers (e.g., metoprolol) appear to lower BP primarily by reducing peripheral vascular resistance; the mechanism is unknown. They may also lower BP by decreasing
myocardial contractility and suppressing reflex tachycardia
(through beta1 blockade in the heart), and by decreasing
renin release (through beta1 blockade in the kidney).
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Calcium channel blockers (e.g., diltiazem, nifedipine) reduce
BP by promoting dilation of arterioles.
ACE inhibitors, ARBs, and DRIs lower BP by preventing
angiotensin II–mediated vasoconstriction and aldosteronemediated volume expansion. ACE inhibitors work by
blocking the formation of angiotensin II, whereas ARBs
block the actions of angiotensin II. DRIs prevent formation
of angiotensin I and thereby shut down the entire RAAS.
Aldosterone antagonists lower BP by preventing aldosteronemediated retention of sodium and water in the kidney.
Thiazide diuretics are preferred drugs for initial therapy
of uncomplicated hypertension.
When a combination of drugs is used for hypertension,
each drug should have a different mechanism of action.
Dosages of antihypertensive drugs should be low initially
and increased gradually. This approach minimizes adverse
effects and permits baroreceptors to reset to a lower
pressure.
Lack of patient adherence is the major cause of treatment
failure in antihypertensive therapy.
Adherence is difficult to achieve because (1) hypertension
has no symptoms (so drug benefits aren’t obvious); (2)
hypertension progresses slowly (so patients think they can
postpone treatment); and (3) treatment is complex and
expensive, continues lifelong, and can cause adverse effects.
A severe hypertensive emergency exists when diastolic
BP exceeds 120 mm Hg and there is ongoing end-organ
damage.
Nitroprusside (IV) is a drug of choice for hypertensive
emergencies.
Hypertension is the most common complication of
pregnancy.
Methyldopa and labetalol are drugs of choice for treating
chronic hypertension of pregnancy.
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526
CHAPTER 47
Drugs for Hypertension
Summary of Major Nursing Implicationsa
ANTIHYPERTENSIVE DRUGS
Preadministration Assessment
Therapeutic Goal
The goal of antihypertensive therapy is to prevent the longterm sequelae of hypertension (heart disease, kidney disease,
stroke) while minimizing drug effects that can reduce quality
of life. For most patients, BP should be reduced to less than
130/80 mm Hg.
Baseline Data
The following tests should be done in all patients: BP;
electrocardiogram; complete urinalysis; hemoglobin and
hematocrit; and blood levels of sodium, potassium, calcium,
creatinine, glucose, uric acid, triglycerides, and cholesterol
(total, LDL, and HDL cholesterol).
Identifying High-Risk Patients
When taking the patient’s drug history, attempt to identify
drugs that can raise BP or that can interfere with the effects
of antihypertensive drugs. Some drugs of concern are listed
later under Minimizing Adverse Interactions.
The patient history should identify comorbid conditions
that either contraindicate the use of specific agents (e.g., AV
block contraindicates use of beta blockers) or require that
drugs be used with special caution (e.g., thiazide diuretics
must be used with caution in patients with gout or diabetes).
For risk factors that pertain to specific antihypertensive drugs,
see the chapters in which those drugs are discussed.
Implementation: Administration
Routes
All drugs for chronic hypertension are administered orally.
Dosage
To minimize adverse effects, dosages should be low initially
and increased gradually. It is counterproductive to employ
high initial dosages that produce a rapid fall in pressure while
also producing intense adverse effects that can discourage
adherence. After 12 months of successful treatment, dosage
reductions should be tried.
Implementation: Measures to Enhance
Therapeutic Effects
Lifestyle Modifications
In hypertensive patients, lifestyle changes can reduce BP and
increase responsiveness to antihypertensive drugs. These
changes should be tried for 6 to 12 months before implementing drug therapy and should continue even if drugs are
required.
Weight Reduction. Help patients develop an exercise
and weight management program if needed.
Sodium Restriction. Encourage patients to consume no
more than 2300 mg of salt daily and provide them with
information on the salt content of foods.
DASH Diet. Encourage patients to adopt a diet rich in
fruits, vegetables, and low-fat dairy products, and low in
total fat, unsaturated fat, and cholesterol.
Alcohol Restriction. Encourage patients to limit alcohol
consumption to 1 ounce/day (for most men) and 0.5 ounce/
day (for women and lighter weight men). One ounce of ethanol
is equivalent to about two mixed drinks, two glasses of wine,
or two cans of beer.
Exercise. Encourage patients with a sedentary lifestyle
to perform 30 to 45 minutes of aerobic exercise (e.g., walking,
swimming, bicycling) most days of the week.
Smoking Cessation. Strongly encourage patients to quit
smoking. Teach patients about aids for smoking cessation
(e.g., nicotine patch, bupropion, varenicline).
Promoting Adherence
Nonadherence is the major cause of treatment failure. Achieving adherence is difficult for several reasons: hypertension
is devoid of overt symptoms; drugs don’t make people
feel better (but can make them feel worse); regimens can
be complex and expensive; complications of hypertension
take years to develop, thereby providing a misguided rationale for postponing treatment; and treatment usually lasts
lifelong.
Provide Patient Education. Educate patients about the
long-term consequences of hypertension and the ability of
lifestyle changes and drug therapy to decrease morbidity
and prolong life. Inform patients that drugs do not cure
hypertension; therefore, the medication prescribed must
usually be taken lifelong.
Encourage Self-Monitoring. Make certain that patients
know the treatment goal (usually reduction of BP to less
than 130/80 mm Hg), and teach them to monitor and chart
their own BP. This will increase their involvement and help
them see the benefits of treatment.
Minimize Adverse Effects. Adverse drug effects are
an obvious deterrent to adherence. Measures to reduce
undesired effects are discussed under Minimizing Adverse
Effects.
Establish a Collaborative Relationship. Encourage
patients to be active partners in setting treatment goals,
creating a treatment program, and evaluating progress.
Simplify the Regimen. An antihypertensive regimen can
consist of several drugs taken multiple times a day. Once an
effective regimen has been established, attempt to switch to
once-a-day or twice-a-day dosing. If an appropriate combination product is available (e.g., a fixed-dose combination of
a thiazide diuretic plus an ACE inhibitor), substitute the
combination product for its components.
Other Measures. Additional measures to promote
adherence include providing positive reinforcement when
treatment goals are achieved, involving family members in
the treatment program, scheduling office visits at convenient
times, following up on patients who miss an appointment,
and devising a program that is effective but keeps costs low.
Continued
527
UNIT VII
Drugs That Affect the Heart, Blood Vessels, and Blood
Summary of Major Nursing Implicationsa—cont’d
Ongoing Evaluation and Interventions
Evaluating Treatment
Monitor BP periodically. The usual goal is to reduce it to
less than 130/80 mm Hg. Teach patients to self-monitor their
BP and to maintain a BP record.
Minimizing Adverse Effects
General Considerations. The fundamental strategy for
decreasing adverse effects is to tailor the regimen to the
sensitivities of the patient. If a drug causes objectionable
effects, a more acceptable drug should be substituted.
Inform patients about the potential side effects of treatment, and encourage them to report objectionable responses.
Avoid drugs that can exacerbate comorbid conditions. For
example, don’t give beta blockers to patients who have
bradycardia, AV block, or asthma. Table 47.5 lists drugs to
avoid in patients with specific disorders.
Initiate therapy with low doses and increase them gradually.
Adverse Effects of Specific Drugs. For measures to
minimize adverse effects of specific antihypertensive drugs
(e.g., beta blockers, diuretics, ACE inhibitors), see the chapters
in which those drugs are discussed.
Minimizing Adverse Interactions
When taking the patient history, identify drugs that can raise
BP or interfere with the effects of antihypertensive drugs.
Drugs of concern include oral contraceptives, nonsteroidal
anti-inflammatory drugs, glucocorticoids, appetite suppressants, tricyclic antidepressants, monoamine oxidase inhibitors,
cyclosporine, erythropoietin, alcohol (in large quantities),
and nasal decongestants and other cold remedies.
Antihypertensive regimens frequently contain two or more
drugs, posing a potential risk of adverse interactions (e.g.,
ACE inhibitors can increase the risk of hyperkalemia caused
by potassium-sparing diuretics). For interactions that pertain
to specific antihypertensive drugs, see the chapters in which
those drugs are discussed.
Patient education information is highlighted as blue text.
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CHAPTER 48
Device Therapy
Implanted Cardioverter-Defibrillators. Cardiac arrest
and fatal ventricular dysrhythmias are relatively common
complications of HF. Accordingly, implantable cardioverterdefibrillators are now recommended for primary or secondary
prevention to reduce mortality in selected patients.
Cardiac Resynchronization. When the left and right
ventricles fail to contract at the same time, cardiac output is
further compromised. Synchronized contractions can be restored
with a biventricular pacemaker. In clinical trials, cardiac
resynchronization improved exercise tolerance and quality of
life and reduced all-cause mortality.
Exercise Training
In the past, bed rest was recommended owing to concern that
physical activity might accelerate progression of LV dysfunction.
However, we now know that inactivity is actually detrimental:
It reduces conditioning, worsens exercise intolerance, and
contributes to HF symptoms. Conversely, studies have shown
that exercise training can improve clinical status, increase
exercise capacity, and improve quality of life. Accordingly,
exercise training should be considered for all stable patients.
Evaluating Treatment
Evaluation is based on symptoms and physical findings. Reductions in dyspnea on exertion, paroxysmal nocturnal dyspnea,
and orthopnea (difficulty breathing, except in the upright
position) indicate success. The physical examination should
assess for reductions in jugular distention, edema, and crackles.
Success is also indicated by increased capacity for physical
activity. Accordingly, patients should be interviewed to determine improvements in the maximal activity they can perform
without symptoms, the type of activity that regularly produces
symptoms, and the maximal activity they can tolerate. (Activity
is defined as walking, stair climbing, activities of daily living,
or any other activity that is appropriate.) Successful treatment
should also improve health-related quality of life in general.
Thus the interview should look for improvements in sleep,
sexual function, outlook on life, cognitive function (alertness,
Drugs for Heart Failure
memory, concentration), and ability to participate in usual
social, recreational, and work activities.
Routine measurement of ejection fraction or maximal
exercise capacity is not recommended. Although the degree
of reduction in ejection fraction measured at the beginning of
therapy is predictive of outcome, improvement in the ejection
fraction does not necessarily indicate the prognosis has changed.
As noted earlier, a reduction in circulating BNP indicates
improvement. The lower BNP is, the better the odds of long-term
survival.
Stage D
Patients in Stage D have advanced structural heart disease and
marked symptoms of HF at rest, despite treatment with maximal
dosages of medications used in Stage C. Repeated and prolonged
hospitalization is common. For eligible candidates, the best
long-term solution is a heart transplant. An implantable LV
mechanical assist device can be used as a “bridge” in patients
awaiting a transplant and to prolong life in those who are not
transplant eligible.
Management focuses largely on the control of fluid retention,
which underlies most signs and symptoms. Intake and output
should be monitored closely, and the patient should be weighed
daily. Fluid retention can usually be treated with a loop diuretic,
perhaps combined with a thiazide. If volume overload becomes
severe, the patient should be hospitalized and given an IV
diuretic. If needed, IV dopamine or IV dobutamine can be
added to increase renal blood flow, thereby enhancing diuresis.
Patients should not be discharged until a stable and effective
oral diuretic regimen has been established.
What about beta blockers and ACE inhibitors? These agents
may be tried, but doses should be low and responses monitored
with care. In Stage D, beta blockers pose a significant risk of
making HF worse, and ACE inhibitors may induce profound
hypotension or renal failure.
When severe symptoms persist despite application of all
recommended therapies, options for end-of-life care should
be discussed with the patient and family.
KEY POINTS
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Heart failure with LV systolic dysfunction, referred to
simply as heart failure (HF) in this chapter, is characterized
by ventricular dysfunction, reduced cardiac output, signs
of inadequate tissue perfusion (fatigue, shortness of breath,
exercise intolerance), and signs of fluid overload (venous
distention, peripheral edema, pulmonary edema).
The initial phase of HF consists of cardiac remodeling—a
process in which the ventricles dilate (grow larger),
hypertrophy (increase in wall thickness), and become more
spherical—coupled with cardiac fibrosis and myocyte death.
As a result of these changes, cardiac output is reduced.
Reduced cardiac output leads to compensatory responses:
(1) activation of the SNS, (2) activation of the RAAS, and
(3) retention of water and expansion of blood volume. As
a result of volume expansion, cardiac dilation increases.
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If the compensatory responses are not sufficient to maintain
adequate production of urine, body water will continue to
accumulate, eventually causing death (from complete
cardiac failure secondary to excessive cardiac dilation and
cardiac edema).
There are three major groups of drugs for heart failure:
diuretics, ACE inhibitors or ARBs, and beta blockers.
Digoxin, which had been used widely in the past, may be
added as indicated.
Diuretics are first-line drugs for all patients with fluid
overload. By reducing blood volume, these drugs can
decrease venous pressure, arterial pressure, pulmonary
edema, peripheral edema, and cardiac dilation.
Although diuretics can reduce symptoms of HF, they do
not prolong survival.
Continued
543
UNIT VII
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Drugs That Affect the Heart, Blood Vessels, and Blood
Thiazide diuretics are ineffective when GFR is low, and
cannot be used if cardiac output is greatly reduced.
Loop diuretics are effective even when GFR is low, and
are preferred to thiazides for most patients.
Thiazide diuretics and loop diuretics can cause hypokalemia
and can increase the risk of digoxin-induced dysrhythmias.
Potassium-sparing diuretics are used to counteract potassium
loss caused by thiazide diuretics and loop diuretics.
Potassium-sparing diuretics can cause hyperkalemia. By
doing so, they can increase the risk of hyperkalemia in
patients taking ACE inhibitors or ARBs.
In patients with HF, ACE inhibitors improve functional
status and reduce mortality. In the absence of specific
contraindications, all patients should be prescribed one.
ACE inhibitors block formation of angiotensin II, promote
accumulation of kinins, and reduce aldosterone release.
As a result, these drugs cause dilation of veins and arterioles,
promote renal excretion of water, and favorably alter cardiac
remodeling.
By dilating arterioles, ACE inhibitors (1) improve regional
blood flow in the kidneys and other tissues and (2) reduce
cardiac afterload, which causes stroke volume and cardiac
output to rise.
By dilating veins, ACE inhibitors reduce venous pressure,
which in turn reduces pulmonary congestion, peripheral
edema, preload, and cardiac dilation.
By suppressing aldosterone release, ACE inhibitors increase
excretion of sodium and water, and decrease excretion of
potassium.
By increasing levels of kinins (and partly by decreasing
levels of angiotensin II), ACE inhibitors can favorably
alter cardiac remodeling.
Major side effects of ACE inhibitors are hypotension,
hyperkalemia, cough, angioedema, and birth defects.
ARBs share the beneficial hemodynamic effects of
ACE inhibitors, but not the beneficial effects on cardiac
remodeling.
In patients with HF, ARBs should be reserved for patients
intolerant of ACE inhibitors (usually owing to cough).
In patients with HF, aldosterone antagonists (e.g., spironolactone, eplerenone) reduce symptoms and prolong life.
Benefits derive from blocking aldosterone receptors in the
heart and blood vessels.
Beta blockers can prolong survival in patients with HF,
and are considered first-line therapy.
To avoid excessive cardiosuppression, beta-blocker dosage
must be very low initially and then gradually increased.
Isosorbide dinitrate (which dilates veins) plus hydralazine
(which dilates arterioles) can be used in place of an ACE
inhibitor (or ARB) if an ACE inhibitor (or ARB) cannot
be used.
BiDil, a fixed-dose combination of hydralazine and isosorbide dinitrate, is approved specifically for treating HF
in African Americans.
Digoxin and other inotropic agents increase the force of
myocardial contraction and thereby increase cardiac output.
Of the available inotropic agents, digoxin is the only one
that is both effective and safe when used orally and the
only one suitable for long-term use.
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Digoxin increases contractility by inhibiting myocardial
Na+/K+-ATPase, thereby (indirectly) increasing intracellular
calcium, which in turn facilitates the interaction of actin
and myosin.
Potassium competes with digoxin for binding to Na+/K+ATPase. Therefore, if potassium levels are low, excessive
inhibition of Na+/K+-ATPase can occur, resulting in toxicity.
Conversely, if potassium levels are high, insufficient
inhibition can occur, resulting in therapeutic failure.
Accordingly, it is imperative to keep potassium levels in
the normal physiologic range: 3.5 to 5 mEq/L.
By increasing cardiac output, digoxin can reverse all of
the overt manifestations of HF: cardiac output improves,
heart rate decreases, heart size declines, constriction of
arterioles and veins decreases, water retention reverses,
blood volume declines, peripheral and pulmonary edema
decrease, water weight is lost, and exercise tolerance
improves. Unfortunately, although digoxin can improve
symptoms, it does not prolong life.
In patients with HF, benefits of digoxin are not due solely
to improved cardiac output; neurohormonal effects are
important too.
Digoxin causes dysrhythmias by altering the electrical
properties of the heart (secondary to inhibition of Na+/K+ATPase).
The most common reason for digoxin-related dysrhythmias
is diuretic-induced hypokalemia.
If a severe digoxin overdose is responsible for dysrhythmias,
digoxin levels can be lowered using Fab antibody fragments
[Digifab].
In addition to dysrhythmias, digoxin can cause GI effects
(anorexia, nausea, vomiting) and CNS effects (fatigue,
visual disturbances). Gastrointestinal and CNS effects often
precede dysrhythmias and therefore can provide advance
warning of serious toxicity.
Digoxin has a narrow therapeutic range.
Digoxin is eliminated by renal excretion.
Although routine monitoring of digoxin levels is generally
unnecessary, monitoring can be helpful when dosage is
changed, symptoms of HF intensify, kidney function
declines, signs of toxicity appear, or drugs that affect digoxin
levels are added to or deleted from the regimen.
Maintenance doses of digoxin are based primarily on
observation of the patient: Doses should be large enough
to minimize symptoms of HF but not so large as to cause
adverse effects.
Maintenance doses of digoxin must be reduced if renal
function declines.
Therapy of Stage C HF has four major goals: (1) relief of
pulmonary and peripheral congestion, (2) improvement of
functional status and quality of life, (3) delay of progression
of cardiac remodeling and LV dysfunction, and (4) prolongation of life.
For routine therapy, Stage C HF is treated with a diuretic,
an ACE inhibitor or an ARB, and a beta blocker.
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544
Summary of Major Nursing Implicationsa
DIGOXIN
Preadministration Assessment
Therapeutic Goal
Digoxin is used to treat HF and dysrhythmias. Be sure to
confirm which disorder the drug has been ordered for.
Baseline Data
Assess for signs and symptoms of HF, including fatigue,
weakness, cough, breathing difficulty (orthopnea, dyspnea on
exertion, paroxysmal nocturnal dyspnea), jugular distention,
and edema.
Determine baseline values for maximal activity without
symptoms, activity that regularly causes symptoms, and
maximal tolerated activity.
Laboratory tests should include an ECG, serum electrolytes,
measurement of ejection fraction, and evaluation of kidney
function.
Identifying High-Risk Patients
Digoxin is contraindicated for patients experiencing ventricular fibrillation, ventricular tachycardia, or digoxin toxicity.
Exercise caution in the presence of conditions that can
predispose the patient to serious adverse responses to digoxin,
such as hypokalemia, partial AV block, advanced HF, or renal
impairment.
Implementation: Administration
Routes
Oral, slow IV injection.
Administration
Oral. Determine heart rate and rhythm before administration. If heart rate is less than 60 beats/min or if a change in
rhythm is detected, withhold digoxin and notify the prescriber.
Warn patients not to “double up” on doses in attempts
to compensate for missed doses.
Intravenous. Monitor cardiac status closely for 1 to 2
hours following IV injection.
Promoting Adherence
Because digoxin has a narrow therapeutic range, rigid adherence to the prescribed dosage is essential. Inform patients
that failure to take digoxin exactly as prescribed may lead
to toxicity or therapeutic failure. If poor adherence is sus-
pected, serum drug levels may help in assessing the extent
of nonadherence.
Implementation: Measures to Enhance
Therapeutic Effects
Advise patients to limit salt intake to 1500 mg/day and to
avoid excessive fluids. Advise patients who drink alcohol to
consume no more than one drink each day. Help patients
establish an appropriate program of regular mild exercise
(e.g., walking, cycling). Precipitating factors for HF (e.g.,
hypertension, valvular heart disease) should be corrected.
Ongoing Evaluation and Interventions
Evaluating Therapeutic Effects
Evaluation is based on symptoms and physical findings. Assess
for reductions in orthopnea, dyspnea on exertion, paroxysmal
nocturnal dyspnea, neck vein distention, edema, and crackles,
and for increased capacity for physical activity. In addition,
Patient education information is highlighted as blue text.
a
assess for improvements in sleep, sexual function, outlook
on life, cognitive function, and ability to participate in social,
recreational, and work activities.
Plasma BNP levels reflect cardiac status: The lower the
level, the better the odds for long-term survival.
Measurement of plasma drug levels can help determine the
cause of therapeutic failure. The optimal range for digoxin
is 0.5 to 0.8 ng/mL.
Minimizing Adverse Effects
Cardiotoxicity. Dysrhythmias are the most serious adverse
effect of digoxin. Monitor hospitalized patients for alterations
in heart rate or rhythm, and withhold digoxin if significant
changes develop.
Inform outpatients about the danger of dysrhythmias.
Teach them to monitor their pulses for rate and rhythm, and
instruct them to notify the prescriber if significant changes
occur. Provide the patient with an ECG rhythm strip; this can
be used by providers unfamiliar with the patient (e.g., when
the patient is traveling) to verify suspected changes in rhythm.
Hypokalemia, usually diuretic induced, is the most frequent
underlying cause of dysrhythmias. Monitor serum potassium
concentrations. If hypokalemia develops, potassium levels can
be raised with potassium supplements, a potassium-sparing
diuretic, or both. Teach patients to recognize early signs of
hypokalemia (e.g., muscle weakness), and instruct them to
notify the prescriber if these develop. Severe vomiting and
diarrhea can increase potassium loss; exercise caution if these
events occur.
To treat digoxin-induced dysrhythmias: (1) withdraw
digoxin and diuretics (make sure that a written order for
digoxin withdrawal is made); (2) administer potassium (unless
potassium levels are above normal or AV block is present); (3)
administer an antidysrhythmic drug (phenytoin or lidocaine,
but not quinidine) if indicated; (4) manage bradycardia with
atropine or electrical pacing; and (5) treat with Fab fragments
if toxicity is life threatening.
Noncardiac Effects. Nausea, vomiting, anorexia, fatigue,
and visual disturbances (blurred or yellow vision) frequently
foreshadow more serious toxicity (dysrhythmias) and should
be reported immediately. Inform patients about these early
indications of toxicity, and instruct them to notify the prescriber if they develop.
Minimizing Adverse Interactions
Diuretics. Thiazide diuretics and loop diuretics increase
the risk of dysrhythmias by promoting potassium loss. Monitor
potassium levels. If hypokalemia develops, it should be
corrected with potassium supplements, a potassium-sparing
diuretic, or both.
ACE Inhibitors and ARBs. These drugs can elevate potassium levels and decrease therapeutic responses to digoxin.
Exercise caution if an ACE inhibitor or ARB is combined
with potassium supplements or a potassium-sparing diuretic.
Sympathomimetic Agents. Sympathomimetic drugs
(e.g., dopamine, dobutamine) stimulate the heart, thereby
increasing the risk of tachydysrhythmias and ectopic pacemaker activity. When sympathomimetics are combined with
digoxin, monitor closely for dysrhythmias.
Quinidine. Quinidine can elevate plasma levels of digoxin.
If quinidine is employed concurrently with digoxin, digoxin
dosage must be reduced. Do not use quinidine to treat digoxininduced dysrhythmias.
UNIT VII
Drugs That Affect the Heart, Blood Vessels, and Blood
KEY POINTS
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Dysrhythmias result from alteration of the electrical
impulses that regulate cardiac rhythm. Antidysrhythmic
drugs control rhythm by correcting or compensating for
these alterations.
In the healthy heart, the SA node is the pacemaker.
Impulses originating in the SA node must travel through
the AV node to reach the ventricles. Impulses arriving at
the AV node are delayed before going on to excite the
ventricles.
The His-Purkinje system conducts impulses rapidly
throughout the ventricles, thereby causing all parts of the
ventricles to contract in near synchrony.
The heart employs two kinds of action potentials: fast
potentials and slow potentials.
Fast potentials occur in the His-Purkinje system, atrial
muscle, and ventricular muscle.
Slow potentials occur in the SA node and AV node.
Phase 0 of fast potentials (depolarization) is generated by
rapid influx of sodium. Because depolarization is fast, these
potentials conduct rapidly.
During phase 2 of fast potentials, calcium enters myocardial
cells, thereby promoting contraction.
Phase 3 of fast potentials (repolarization) is generated by
rapid extrusion of potassium.
Phase 0 of slow potentials (depolarization) is caused by
slow influx of calcium. Because depolarization is slow,
these potentials conduct slowly.
Spontaneous phase 4 depolarization—of fast or slow
potentials—gives cells automaticity.
Spontaneous phase 4 depolarization of cells in the SA
node normally determines heart rate.
The P wave of an ECG is caused by depolarization of the
atria.
The QRS complex is caused by depolarization of the
ventricles. Widening of the QRS complex indicates slowed
conduction through the ventricles.
The T wave is caused by repolarization of the ventricles.
The PR interval represents the time between onset of the
P wave and onset of the QRS complex. PR prolongation
indicates delayed AV conduction.
The QT interval represents the time between onset of the
QRS complex and completion of the T wave. QT prolongation indicates delayed ventricular repolarization.
Dysrhythmias arise from disturbances of impulse formation
(automaticity) or impulse conduction.
Reentrant dysrhythmias result from a localized, selfsustaining circuit capable of repetitive cardiac stimulation.
Tachydysrhythmias can be divided into two major groups:
supraventricular tachydysrhythmias and ventricular tachydysrhythmias. In general, ventricular tachydysrhythmias
disrupt cardiac pumping more than do supraventricular
tachydysrhythmias.
Treatment of supraventricular tachydysrhythmias is often
directed at blocking impulse conduction through the AV
node, rather than at eliminating the dysrhythmia.
Treatment of ventricular dysrhythmias is usually directed
at eliminating the dysrhythmia.
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564
All antidysrhythmic drugs are also prodysrhythmic (proarrhythmic). That is, they all can worsen existing dysrhythmias
and generate new ones.
Class I antidysrhythmic drugs block cardiac sodium channels and thereby slow impulse conduction through the
atria, ventricles, and His-Purkinje system.
Slowing ventricular conduction widens the QRS complex.
Quinidine (a class IA drug) blocks sodium channels and
delays ventricular repolarization. Delaying ventricular
repolarization prolongs the QT interval.
Quinidine causes diarrhea and other GI symptoms in 33%
of patients. These effects frequently force drug withdrawal.
Quinidine can cause dysrhythmias. Widening of the QRS
complex (by 50% or more) and excessive prolongation of
the QT interval are warning signs.
Quinidine can raise digoxin levels. If the drugs are used
together, digoxin dosage must be reduced.
Class IB agents differ from class IA agents in two ways:
they accelerate repolarization and have little or no effect
on the ECG.
Lidocaine (a class IB agent) is used only for ventricular
dysrhythmias. The drug is not active against supraventricular
dysrhythmias.
Lidocaine undergoes rapid inactivation by the liver. As a
result, it must be administered by continuous IV infusion.
Propranolol and other class II drugs block cardiac beta1
receptors.
By blocking cardiac beta1 receptors, propranolol attenuates
sympathetic stimulation of the heart and thereby decreases
SA nodal automaticity, AV conduction velocity, and
myocardial contractility.
By decreasing AV conduction velocity, propranolol prolongs
the PR interval.
The effects of propranolol on the heart result (ultimately)
from suppressing calcium entry. Therefore, the cardiac
effects of propranolol and the effects of calcium channel
blockers are nearly identical.
Propranolol is especially useful for treating dysrhythmias
caused by excessive sympathetic stimulation of the heart.
In patients with supraventricular tachydysrhythmias,
propranolol helps by (1) slowing discharge of the SA node
and (2) decreasing impulse conduction through the AV
node, which prevents the atria from driving the ventricles
at an excessive rate.
Class III antidysrhythmics block potassium channels and
thereby delay repolarization of fast potentials. As a result,
they prolong the action potential duration and the effective
refractory period. By delaying ventricular repolarization,
they prolong the QT interval.
Amiodarone (a class III agent) is highly effective against
atrial and ventricular dysrhythmias, but can cause multiple
serious adverse effects, including damage to the lungs,
eyes, liver, and thyroid.
Dronedarone, a derivative of amiodarone, is somewhat
less toxic than amiodarone, but also less effective. In
patients with heart failure or permanent atrial fibrillation,
dronedarone doubles the risk of death.
CHAPTER 49
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Verapamil and diltiazem (class IV antidysrhythmics) block
cardiac calcium channels and thereby reduce automaticity
of the SA node, slow conduction through the AV node,
and decrease myocardial contractility. These effects are
identical to those of the beta blockers.
By suppressing AV conduction, verapamil and diltiazem
prolong the PR interval.
Verapamil and diltiazem are used to slow ventricular rate
in patients with atrial fibrillation or atrial flutter and to
terminate SVT caused by an AV nodal reentrant circuit.
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Antidysrhythmic Drugs
In both cases, benefits derive from suppressing AV nodal
conduction.
Adenosine is a drug of choice for terminating paroxysmal
SVT.
Adenosine has a very short half-life (less than 10 seconds)
and must be given by IV bolus.
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Summary of Major Nursing Implicationsa
Summaries are limited to the major antidysrhythmic drugs.
Summaries for beta blockers (propranolol, acebutolol, and
esmolol), phenytoin, calcium channel blockers (verapamil
and diltiazem), and digoxin appear in Chapters 18, 24, 45,
and 48, respectively.
QUINIDINE
Preadministration Assessment
Therapeutic Goal
The usual goal is long-term suppression of atrial and ventricular dysrhythmias.
Baseline Data
Obtain a baseline ECG and laboratory evaluation of liver
function. Determine blood pressure.
Identifying High-Risk Patients
Quinidine is contraindicated for patients with a history of
hypersensitivity to quinidine or other cinchona alkaloids and
for patients with complete heart block, digoxin toxicity, or
conduction disturbances associated with marked QRS widening
and QT prolongation.
Exercise caution in patients with partial AV block, HF,
hypotensive states, and hepatic dysfunction.
Minimizing Adverse Effects
Diarrhea. Diarrhea and other GI disturbances occur in
one-third of patients and frequently force drug withdrawal.
Inform patients that they can reduce GI effects by taking
quinidine with meals.
Cinchonism. Inform patients about symptoms of cinchonism (tinnitus, headache, nausea, vertigo, disturbed vision),
and instruct them to notify the prescriber if these develop.
Cardiotoxicity. Monitor the ECG for signs of cardiotoxicity, especially widening of the QRS complex (by 50% or
more) and excessive prolongation of the QT interval. Monitor
pulses for significant changes in rate or regularity. If signs
of cardiotoxicity develop, withhold quinidine and notify the
prescriber.
Arterial Embolism. Embolism may occur during therapy
of atrial fibrillation. Risk is reduced by treatment with an
anticoagulant (e.g., warfarin, dabigatran). Observe for signs
of thromboembolism (e.g., sudden chest pain, dyspnea), and
report these immediately.
Minimizing Adverse Interactions
Digoxin. Quinidine can double digoxin levels. When these
drugs are combined, digoxin dosage should be reduced.
Monitor patients for digoxin toxicity (dysrhythmias).
PROCAINAMIDE
Implementation: Administration
Routes
Usual Route. Oral.
Rare Routes. IM and IV.
Administration
Advise patients to take quinidine with meals. Warn them
not to crush or chew sustained-release formulations.
Dosage size depends on the particular quinidine salt being
used: 200 mg of quinidine sulfate is equivalent to 275 mg
of quinidine gluconate.
Ongoing Evaluation and Interventions
Evaluating Therapeutic Effects
Monitor for beneficial changes in the ECG. Plasma drug
levels should be kept between 2 and 5 mcg/mL.
Preadministration Assessment
Therapeutic Goal
Procainamide is indicated for acute and long-term management
of ventricular and supraventricular dysrhythmias. Because
procainamide can be toxic with long-term use, quinidine is
preferred to procainamide for chronic suppression.
Baseline Data
Obtain a baseline ECG, complete blood count, and laboratory
evaluations of liver and kidney function. Determine blood
pressure.
Identifying High-Risk Patients
Procainamide is contraindicated for patients with systemic
lupus erythematosus (SLE), complete AV block, and secondContinued
565
UNIT VII
Drugs That Affect the Heart, Blood Vessels, and Blood
Summary of Major Nursing Implicationsa—cont’d
degree or third-degree AV block in the absence of an electronic pacemaker, and patients with a history of procaine
allergy.
Exercise caution in patients with hepatic or renal
dysfunction.
LIDOCAINE
Implementation: Administration
Routes
Oral, IM, IV.
Baseline Data
Obtain a baseline ECG and determine blood pressure.
Administration
Instruct patients to administer procainamide at evenly spaced
intervals around-the-clock. Warn patients not to crush or
chew sustained-release formulations.
When switching from IV procainamide to oral procainamide, allow 3 hours to elapse between stopping the infusion
and giving the first oral dose.
Give IM injections deep into the gluteal muscle.
Ongoing Evaluation and Interventions
Evaluating Therapeutic Effects
Monitor the ECG for beneficial changes. Plasma drug levels
should be kept between 3 and 10 mcg/mL.
Minimizing Adverse Effects
SLE-like Syndrome. Prolonged therapy can produce a
syndrome resembling SLE. Inform patients about manifesta-
tions of SLE (joint pain and inflammation; hepatomegaly;
unexplained fever; soreness of the mouth, throat, or gums),
and instruct them to notify the prescriber if these develop.
If SLE is diagnosed, procainamide should be discontinued.
If discontinuation is impossible, signs and symptoms can be
controlled with a nonsteroidal anti-inflammatory drug (e.g.,
aspirin) or a glucocorticoid. The ANA titer should be measured
periodically, and if it rises, procainamide withdrawal should
be considered.
Blood Dyscrasias. Procainamide can cause agranulocytosis, thrombocytopenia, and neutropenia. Deaths have
occurred. Obtain complete blood counts weekly during the
first 3 months of treatment and periodically thereafter. Instruct
patients to inform the prescriber at the first sign of infection
(fever, chills, sore throat), bruising, or bleeding. If subsequent
blood counts indicate hematologic disturbance, discontinue
procainamide immediately.
Cardiotoxicity. Procainamide can cause dysrhythmias.
Monitor pulses for changes in rate or regularity. Monitor the
ECG for excessive QRS widening (greater than 50%) and
for PR prolongation. If these occur, withhold procainamide
and notify the prescriber.
Arterial Embolism. Embolism may occur during therapy
of atrial fibrillation. Risk is reduced by treatment with an
anticoagulant (e.g., warfarin, dabigatran). Observe for signs
of thromboembolism (e.g., sudden chest pain, dyspnea), and
report these immediately.
Preadministration Assessment
Therapeutic Goal
Acute management of ventricular dysrhythmias.
Identifying High-Risk Patients
Lidocaine is contraindicated for patients with Stokes-Adams
syndrome, Wolff-Parkinson-White syndrome, and severe
degrees of SA, AV, or intraventricular block in the absence
of electronic pacing.
Exercise caution in patients with hepatic dysfunction or
impaired hepatic blood flow.
Implementation: Administration
Routes
Usual. IV.
Emergencies. IM.
Administration
Intravenous. Make certain the lidocaine preparation is
labeled for IV use (i.e., is devoid of preservatives and catecholamines). Dilute concentrated preparations with 5% dextrose
in water.
The initial dose is 50 to 100 mg (1 mg/kg) infused at a
rate of 25 to 50 mg/min. For maintenance, monitor the ECG
and adjust the infusion rate on the basis of cardiac response.
The usual rate is 1 to 4 mg/min.
Intramuscular. Reserve for emergencies. The usual dose
is 300 mg injected into the deltoid muscle. Switch to IV
lidocaine as soon as possible.
Ongoing Evaluation and Interventions
Evaluating Therapeutic Effects
Continuous ECG monitoring is required. Plasma drug levels
should be kept between 1.5 and 5 mcg/mL.
Minimizing Adverse Effects
Excessive doses can cause convulsions and respiratory arrest.
Equipment for resuscitation should be available. Seizures
can be managed with diazepam.
AMIODARONE
Preadministration Assessment
Therapeutic Goal
Oral Therapy. Long-term treatment of (1) atrial fibrillation
and (2) life-threatening recurrent ventricular fibrillation or
recurrent hemodynamically unstable ventricular tachycardia
in patients who have not responded to safer drugs.
Intravenous Therapy. Initial treatment of recurrent
ventricular fibrillation, shock-resistant ventricular fibrillation,
566
CHAPTER 49
Antidysrhythmic Drugs
Summary of Major Nursing Implicationsa—cont’d
recurrent hemodynamically unstable ventricular tachycardia,
atrial fibrillation, and AV nodal reentrant tachycardia.
Baseline Data
Obtain a baseline ECG, eye examination, and chest x-ray,
along with potassium and magnesium levels, and tests for
thyroid, pulmonary, and liver function.
Identifying High-Risk Patients
Amiodarone is contraindicated for patients with severe sinus
node dysfunction or second- or third-degree AV block, and
for women who are pregnant or breast-feeding.
Exercise caution in patients with thyroid disorders,
hypokalemia, or hypomagnesemia.
Implementation: Administration
Routes
Oral. Used for maintenance therapy of atrial and ventricular dysrhythmias.
Intravenous. Used for acute therapy of atrial and ventricular dysrhythmias.
Administration and Dosage
Oral. Initiate treatment in a hospital. High doses are used
initially (800 to 1600 mg/day for 1 to 3 weeks). The usual
maintenance dosage is 400 mg/day.
Intravenous. Administer by continuous IV infusion,
starting with a rapid infusion rate and later reducing the rate
for maintenance. Intravenous treatment may last from 2 days
to 3 weeks.
Ongoing Evaluation and Interventions
Evaluating Therapeutic Effects
Monitor for beneficial changes in the ECG.
Minimizing Adverse Effects
Pulmonary Toxicity. Amiodarone can cause potentially
fatal lung damage (hypersensitivity pneumonitis, interstitial/
alveolar pneumonitis, and pulmonary fibrosis). Obtain a
baseline chest x-ray and pulmonary function test, and monitor
pulmonary function throughout treatment. Inform patients
about signs of lung injury (dyspnea, cough, chest pain), and
instruct them to report these immediately. Treatment consists
of withdrawing amiodarone and providing supportive care,
sometimes including glucocorticoids.
Cardiotoxicity. Amiodarone can cause HF and atrial and
ventricular dysrhythmias. Patients with pre-existing heart
failure must not use the drug. Warn patients about signs of
HF (e.g., shortness of breath, reduced exercise tolerance,
fatigue, tachycardia, weight gain), and instruct them to report
these immediately.
Liver Toxicity. Amiodarone can injure the liver. Obtain
tests of liver function at baseline and periodically during
treatment. If circulating liver enzymes exceed 3 times the
normal level, amiodarone should be withdrawn. Inform
patients about signs and symptoms of liver injury (e.g.,
anorexia, nausea, vomiting, malaise, fatigue, itching, jaundice,
dark urine), and instruct them to report them immediately.
Thyroid Toxicity. Amiodarone can cause hypothyroidism
and hyperthyroidism. Obtain tests of thyroid function at
baseline and periodically during treatment. Treat hypothyroidism with thyroid hormone supplements. Treat hyperthyroidism
with an antithyroid drug (e.g., methimazole) or thyroidectomy.
Stopping amiodarone should be considered.
Toxicity in Pregnancy and Breast-Feeding. Amiodarone
can harm the developing fetus and breast-feeding infant. Warn
patients to avoid pregnancy and breast-feeding while using
amiodarone and for several months after stopping.
Ophthalmic Effects. Amiodarone has been associated with
optic neuropathy and optic neuritis, sometimes progressing
to blindness. Obtain ophthalmic tests, including funduscopy
and a slit-lamp examination, at baseline and periodically
during treatment. Advise patients to report reductions in visual
acuity or peripheral vision. If optic neuropathy or neuritis is
diagnosed, discontinuing amiodarone should be considered.
Virtually all patients develop corneal microdeposits. In
most cases, the deposits have no effect on vision and thus
only rarely lead to the discontinuation of amiodarone.
Dermatologic Effects. Photosensitivity reactions are
common. Advise patients to avoid sunlamps and to wear
sunscreen and protective clothing when outdoors. With
prolonged sun exposure, skin may develop a bluish-gray
discoloration, which typically resolves a few months after
amiodarone is stopped.
Minimizing Adverse Interactions
Amiodarone is subject to significant interactions with many
drugs. Interactions of special concern are presented here.
Drugs Whose Levels Can Be Increased by Amiodarone. Amiodarone can increase levels of several drugs,
including quinidine, procainamide, phenytoin, digoxin, diltiazem, warfarin, cyclosporine, and three statins: lovastatin,
simvastatin, and atorvastatin. Dosages of these agents often
require reduction.
Drugs That Can Reduce Amiodarone Levels. Amiodarone levels can be reduced by cholestyramine (which
decreases amiodarone absorption) and by agents that induce
CYP3A4 (e.g., St. John’s wort, rifampin). Monitor to ensure
that amiodarone is still effective.
Drugs That Can Increase the Risk of Dysrhythmias. The risk of severe dysrhythmias is increased by diuretics
(because they can reduce levels of potassium and magnesium)
and by drugs that prolong the QT interval.
Drugs That Can Cause Bradycardia. Combining amiodarone with a beta blocker, verapamil, or diltiazem can lead
to excessive slowing of heart rate.
Grapefruit Juice. Grapefruit juice inhibits CYP3A4 and
can raise levels of amiodarone. Toxicity can result. Advise
patients to avoid grapefruit juice.
Patient education information is highlighted as blue text.
a
567
UNIT VII
Drugs That Affect the Heart, Blood Vessels, and Blood
KEY POINTS
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Lipoproteins are structures that transport lipids (cholesterol
and triglycerides [TGs]) in blood.
Lipoproteins consist of a hydrophobic core, a hydrophilic
shell, plus at least one apolipoprotein, which serves as a
recognition site for receptors on cells.
Lipoproteins that contain apolipoprotein B-100 transport
cholesterol and/or TGs from the liver to peripheral tissues.
Lipoproteins that contain apolipoproteins A-I or A-II
transport cholesterol from peripheral tissues back to the
liver.
There are three major types of lipoproteins: VLDLs (verylow-density lipoproteins), LDLs (low-density lipoproteins),
and HDLs (high-density lipoproteins).
VLDLs transport TGs to peripheral tissues.
The contribution of VLDLs to ASCVD is unclear.
LDLs transport cholesterol to peripheral tissues.
Elevation of LDL cholesterol greatly increases the risk of
ASCVD.
By reducing LDL cholesterol levels, we can arrest or reverse
atherosclerosis, and can thereby reduce morbidity and
mortality from ASCVD.
HDLs transport cholesterol back to the liver.
HDLs protect against ASCVD.
Atherogenesis is a chronic inflammatory process that begins
with accumulation of LDLs beneath the arterial endothelium, followed by oxidation of LDLs.
All adults older than 20 years should be screened every 5
years for total cholesterol, LDL cholesterol, HDL cholesterol, and TGs.
Treatment of high LDL cholesterol is based on the individual’s 10-year risk of having a major coronary event.
Individuals with established ASCVD or an ASCVD risk
equivalent (e.g., diabetes) are in the highest 10-year risk
group.
Diet modification along with exercise is the primary method
for reducing LDL cholesterol. Drugs are employed only
if diet modification and exercise fail to reduce LDL
cholesterol to the target level.
Therapy with cholesterol-lowering drugs must continue
lifelong. If these drugs are withdrawn, cholesterol levels
will return to pretreatment values.
Statins (HMG-CoA reductase inhibitors) are the most
effective drugs for lowering LDL cholesterol, and they
cause few adverse effects.
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Statins can slow progression of ASCVD, decrease the
number of adverse cardiac events, and reduce mortality.
Statins reduce LDL cholesterol levels by increasing the
number of LDL receptors on hepatocytes, thereby enabling
hepatocytes to remove more LDLs from the blood. The
process by which LDL receptor number is increased begins
with inhibition of HMG-CoA reductase, the rate-limiting
enzyme in cholesterol synthesis.
Four statins—atorvastatin, fluvastatin, lovastatin, and
simvastatin—are metabolized by CYP3A4, and hence their
levels can be increased by CYP3A4 inhibitors (e.g.,
cyclosporine, erythromycin, ketoconazole, ritonavir).
Statins can cause liver damage. Tests of liver function should
be done at baseline and as clinically indicated thereafter.
Statins can cause myopathy. Patients who experience
unusual muscle pain, soreness, tenderness, and/or weakness
should inform their provider. A marker for muscle injury—
creatine kinase (CK)—should be measured at baseline,
before starting the drug, and whenever signs or symptoms
that could be due to myositis or myopathy develop.
Statins should not be used during pregnancy.
Bile-acid sequestrants (e.g., colesevelam) reduce LDL cholesterol levels by increasing the number of LDL receptors
on hepatocytes. The mechanism is complex and begins
with preventing reabsorption of bile acids in the intestine.
Bile-acid sequestrants are not absorbed from the GI tract,
and hence do not cause systemic adverse effects. However,
they can cause constipation and other GI effects. (GI effects
with one agent—colesevelam—are minimal.)
Older bile-acid sequestrants form complexes with other
drugs and thereby prevent their absorption. Accordingly,
oral medications should be administered 1 hour before the
sequestrant or 4 hours after. With a newer sequestrant—
colesevelam—these interactions are minimal.
Ezetimibe lowers LDL cholesterol by reducing cholesterol
absorption in the small intestine.
Like the statins, ezetimibe can cause muscle injury.
Gemfibrozil and other fibrates are the most effective drugs
for lowering TG levels.
Like the statins, the fibrates can cause muscle injury.
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Summary of Major Nursing Implicationsa
IMPLICATIONS THAT APPLY TO ALL DRUGS
THAT LOWER LDL CHOLESTEROL
Preadministration Assessment
Baseline Data
Obtain laboratory values for total cholesterol, LDL cholesterol,
HDL cholesterol, and TGs (VLDLs).
Identifying ASCVD Risk Factors
The patient history and physical examination should identify
ASCVD risk factors. These include smoking, advancing age,
a personal history of ASCVD, reduced levels of HDL cholesterol (below 40 mg/dL), and hypertension.
In the past, diabetes was considered an ASCVD risk factor.
However, because the association between diabetes and
588
CHAPTER 50
Prophylaxis of Atherosclerotic Cardiovascular Disease
Summary of Major Nursing Implicationsa—cont’d
ASCVD is so strong, diabetes is now considered an ASCVD
risk equivalent (i.e., it poses the same 10-year risk of a major
coronary event as ASCVD itself).
Measures to Enhance Therapeutic Effects
Diet Modification
Diet modification should precede and accompany drug therapy
for elevated LDL cholesterol. Inform patients about the
importance of diet in controlling cholesterol levels, and arrange
for dietary counseling. Advise patients to limit consumption
of cholesterol (to below 200 mg/day) and saturated fat (to
below 7% of caloric intake). If these measures fail to reduce
LDL cholesterol to the target level, advise patients to add
soluble fiber and plant stanols or sterols to the regimen.
Exercise
Regular exercise can reduce LDL cholesterol and elevate
HDL cholesterol, reducing the risk of ASCVD. Help the
patient establish an appropriate exercise program.
Reduction of ASCVD Risk Factors
Correctable ASCVD risk factors should be addressed. Encourage smokers to quit. Disease states that promote ASCVD—
diabetes mellitus and hypertension—must be treated.
Promoting Compliance
Drug therapy for elevated LDL cholesterol must continue
lifelong; if drugs are withdrawn, cholesterol levels will return
to pretreatment values. Inform patients about the need for
continuous therapy, and encourage them to adhere to the
prescribed regimen.
HMG-COA REDUCTASE INHIBITORS (STATINS)
Atorvastatin
Fluvastatin
Lovastatin
Pitavastatin
Pravastatin
Rosuvastatin
Simvastatin
Exercise caution in patients with nonalcoholic fatty liver
disease, in those who consume alcohol to excess, and in
those taking fibrates or ezetimibe or agents that inhibit
CYP3A4 (e.g., cyclosporine, erythromycin, ketoconazole,
ritonavir). Use rosuvastatin with caution in Asian patients.
Implementation: Administration
Route
Oral.
Administration
Instruct patients to take lovastatin with the evening meal;
all other statins can be administered without regard to meals.
Advise patients that dosing in the evening is preferred for
all statins.
Ongoing Evaluation and Interventions
Evaluating Therapeutic Effects
Cholesterol levels should be monitored monthly early in
treatment and at longer intervals thereafter.
Minimizing Adverse Effects
Statins are very well tolerated. Side effects are uncommon,
and serious adverse effects—hepatotoxicity and myopathy—
are relatively rare.
Hepatotoxicity. Statins can injure the liver, but jaundice
and other clinical signs are rare. Liver function should be
assessed before treatment and as clinically indicated thereafter.
If serum transaminase becomes persistently excessive (more
than 3 times the ULN), statins should be discontinued. Statins
should be avoided in patients with alcoholic or viral hepatitis,
but may be used in patients with nonalcoholic fatty liver
disease.
Myopathy. Statins can cause muscle injury. If statins are
not withdrawn, injury may progress to severe myositis or
potentially fatal rhabdomyolysis. Inform patients about the
risk of myopathy, and instruct them to notify the prescriber
if unexplained muscle pain or tenderness develops. If muscle
In addition to the implications discussed below, see earlier
in this summary for implications that apply to all drugs that
lower LDL cholesterol.
Preadministration Assessment
Therapeutic Goal
Statins, in combination with diet modification and exercise,
are used primarily to lower levels of LDL cholesterol.
Additional indications are shown in Table 50.7.
Baseline Data
Obtain a baseline lipid profile, consisting of total cholesterol,
LDL cholesterol, HDL cholesterol, and TGs (VLDLs). Also,
obtain baseline LFTs and a CK level.
Identifying High-Risk Patients
Statins are contraindicated for patients with viral or alcoholic
hepatitis and for women who are pregnant.
pain does develop, the CK level should be measured, and if
it is more than 10 times the ULN, the statin should be
withdrawn or changed.
Minimizing Adverse Interactions
The risk of myopathy is increased by (1) gemfibrozil, fenofibrate, and ezetimibe, which promote myopathy themselves;
and by (2) inhibitors of CYP3A4—such as cyclosporine,
macrolide antibiotics (e.g., erythromycin), azole antifungal
drugs (e.g., ketoconazole), and HIV protease inhibitors (e.g.,
ritonavir)—which can cause statin levels to rise. The combination of a statin with any of these drugs should be used with
caution.
Use in Pregnancy
Statins are contraindicated during pregnancy. Inform women
of childbearing age about the potential for fetal harm and
warn them against becoming pregnant. If pregnancy occurs
and the patient intends to continue the pregnancy, statins
should be withdrawn.
589
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UNIT VII
Drugs That Affect the Heart, Blood Vessels, and Blood
Summary of Major Nursing Implicationsa—cont’d
BILE-ACID SEQUESTRANTS
GEMFIBROZIL
Cholestyramine
Colesevelam
Colestipol
Preadministration Assessment
Therapeutic Goal
Gemfibrozil, in conjunction with diet modification, is used
to reduce elevated levels of TGs (VLDLs). The drug is not
very effective at lowering LDL cholesterol. It may also be
used to raise low levels of HDL cholesterol.
In addition to the implications discussed here, see earlier in
this summary for implications that apply to all drugs that
lower LDL cholesterol.
Preadministration Assessment
Therapeutic Goal
Bile-acid sequestrants, in conjunction with diet modification
and exercise (and a statin if necessary), are used to reduce
elevated levels of LDL cholesterol.
Baseline Data
Obtain laboratory values for total cholesterol, LDL cholesterol,
HDL cholesterol, and TGs (VLDLs).
Implementation: Administration
Route
Oral.
Baseline Data
Obtain laboratory values for total cholesterol, LDL cholesterol,
HDL cholesterol, and TGs (VLDLs).
Identifying High-Risk Patients
Gemfibrozil is contraindicated for patients with liver disease,
severe renal dysfunction, and gallbladder disease.
Use with caution in patients taking statins or warfarin.
Implementation: Administration
Route
Oral.
Administration
Administration
Instruct patients to mix cholestyramine powder and colestipol
granules with water, fruit juice, soup, or pulpy fruit (e.g.,
applesauce, crushed pineapple) to reduce the risk of esophageal irritation and impaction. Inform patients that the
sequestrants are not water soluble, so the mixtures will be
cloudy suspensions, not clear solutions.
Ongoing Evaluation and Interventions
Evaluating Therapeutic Effects
Cholesterol levels should be monitored monthly early in
treatment and at longer intervals thereafter.
Minimizing Adverse Effects
Constipation. Cholestyramine and colestipol—but not
colesevelam—can cause constipation. Inform patients that
constipation can be minimized by increasing dietary fiber
and fluids. A mild laxative may be used if needed. Instruct
patients taking cholestyramine or colestipol to notify the
prescriber if constipation becomes bothersome, in which case
a switch to colesevelam should be considered.
Vitamin Deficiency. Cholestyramine and colestipol—but
not colesevelam—can impair absorption of fat-soluble vitamins
(A, D, E, and K). Vitamin supplements may be required.
Colesevelam does not reduce vitamin absorption.
Minimizing Adverse Interactions
Cholestyramine and colestipol—but not colesevelam—can
bind with other drugs and prevent their absorption. Advise
patients to administer other medications 1 hour before these
sequestrants or 4 hours after.
Instruct patients to administer gemfibrozil 30 minutes before
the morning and evening meals.
Ongoing Evaluation and Interventions
Evaluating Therapeutic Effects
Obtain periodic tests of blood lipids.
Minimizing Adverse Effects
Gallstones. Gemfibrozil increases gallstone development.
Inform patients about symptoms of gallbladder disease (e.g.,
upper abdominal discomfort, intolerance of fried foods,
bloating), and instruct them to notify the prescriber if these
develop.
Myopathy. Gemfibrozil can cause muscle damage. Warn
patients to report any signs of muscle injury, such as tenderness, weakness, or unusual muscle pain.
Liver Disease. Gemfibrozil may disrupt liver function.
Cancer of the liver may also be a risk. Obtain periodic tests
of liver function.
Minimizing Adverse Interactions
Warfarin. Gemfibrozil enhances the effects of warfarin,
thereby increasing the risk of bleeding. Obtain more frequent
measurements of prothrombin time and assess the patient for
signs of bleeding. Reduction of warfarin dosage may be
required, and reassessment and readjustment of the warfarin
dosage may be needed if the fibrate is stopped.
Statins. Gemfibrozil and statins both cause muscle injury.
Risks rise when both are used. Use the combination with
caution.
Patient education information is highlighted as blue text.
a
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CHAPTER 51
reduce cholesterol reduce that risk. Accordingly, all patients
with high cholesterol levels should receive cholesterol-lowering
therapy.
Hypertension. High blood pressure increases the risk of
cardiovascular mortality, and lowering blood pressure reduces
the risk. Accordingly, all patients with hypertension should
receive treatment. Blood pressure should be reduced to
140/90 mm Hg or less. In patients with additional risk factors
(e.g., diabetes, heart failure, retinopathy), the target blood
pressure is 130/80 mm Hg or less. Management of hypertension
is discussed in Chapter 47.
Diabetes. Both type 1 (insulin-dependent) and type 2
(non–insulin-dependent) diabetes increase the risk of cardiovascular mortality. Type 1 increases the risk 3- to 10-fold; type
2 increases the risk 2- to 4-fold. Although there is good evidence
that tight glycemic control decreases the risk of microvascular
complications of diabetes, there is little evidence to show that
tight glycemic control decreases the risk of cardiovascular
complications. Nonetheless, it is prudent to strive for optimal
glycemic control.
Drugs for Angina Pectoris
Physical Inactivity. Increased physical activity has multiple benefits. In patients with chronic stable angina, exercise
increases exercise tolerance and the sense of well-being, and
decreases anginal symptoms, cholesterol levels, and objective
measures of ischemia. Accordingly, the guidelines recommend
that patients perform 30 to 60 minutes of a moderate-intensity
activity 3 to 4 times a week. Such activities include walking,
jogging, cycling, and other aerobic exercises. Exercise by
moderate- to high-risk patients should be medically supervised.
Management of Variant Angina
Treatment of vasospastic angina can proceed in three steps.
For initial therapy, either a calcium channel blocker or a longacting nitrate is selected. If either drug alone is inadequate,
then combined therapy with a calcium channel blocker plus a
nitrate should be tried. If the combination fails to control
symptoms, CABG surgery may be indicated. Beta blockers
are not effective in vasospastic angina.
KEY POINTS
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Anginal pain occurs when cardiac oxygen supply is insufficient to meet cardiac oxygen demand.
Cardiac oxygen demand is determined by heart rate,
contractility, preload, and afterload. Drugs that reduce these
factors can help relieve anginal pain.
Cardiac oxygen supply is determined by myocardial blood
flow. Drugs that increase oxygen supply will reduce anginal
pain.
Angina pectoris has three forms: chronic stable angina,
variant (vasospastic) angina, and unstable angina.
The underlying cause of stable angina is coronary artery
atherosclerosis.
The underlying cause of variant angina is coronary artery
spasm.
Drugs relieve pain of stable angina by decreasing cardiac
oxygen demand. They do not increase oxygen supply.
Drugs relieve pain of variant angina by increasing cardiac
oxygen supply. They do not decrease oxygen demand.
Nitroglycerin and other organic nitrates are vasodilators.
To cause vasodilation, nitroglycerin must first be converted
to nitric oxide, its active form. This reaction requires a
sulfhydryl source.
Nitroglycerin relieves pain of stable angina by dilating
veins, which decreases venous return, which decreases
preload, which decreases oxygen demand.
Nitroglycerin relieves pain of variant angina by relaxing
coronary vasospasm, which increases oxygen supply.
Nitroglycerin is highly lipid soluble, and therefore is readily
absorbed through the skin and oral mucosa.
Nitroglycerin undergoes very rapid inactivation in the
liver. Hence, when the drug is administered orally, most
of each dose is destroyed before reaching the systemic
circulation.
When nitroglycerin is administered sublingually, it is
absorbed directly into the systemic circulation and therefore
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temporarily bypasses the liver. Hence, to produce equivalent
effects, sublingual doses can be much smaller than oral
doses.
Nitroglycerin causes three characteristic side effects:
headache, orthostatic hypotension, and reflex tachycardia.
All three occur secondary to vasodilation.
Reflex tachycardia from nitroglycerin can be prevented
with a beta blocker, verapamil, or diltiazem.
Continuous use of nitroglycerin can produce tolerance
within 24 hours. The mechanism may be depletion of
sulfhydryl groups.
To prevent tolerance, nitroglycerin should be used in the
lowest effective dosage, and long-acting formulations should
be used on an intermittent schedule that allows at least 8
drug-free hours every day, usually during the night.
Nitroglycerin preparations that have a rapid onset (e.g.,
sublingual nitroglycerin) are used to abort an ongoing
anginal attack and to provide acute prophylaxis when
exertion is expected. Administration is PRN.
Nitroglycerin preparations that have a long duration (e.g.,
patches, sustained-release oral capsules) are used for
extended protection against anginal attacks. Administration
is on a fixed schedule (but one that allows at least 8 drugfree hours a day).
Nitroglycerin should be used cautiously with most vasodilators and must not be used at all with sildenafil [Viagra]
and other PDE5 inhibitors.
Beta blockers prevent pain of stable angina primarily by
decreasing heart rate and contractility, which reduces cardiac
oxygen demand.
Beta blockers are administered on a fixed schedule,
not PRN.
Beta blockers are not used for variant angina.
CCBs relieve the pain of stable angina by reducing cardiac
oxygen demand. Two mechanisms are involved. First, all
Continued
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UNIT VII
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Drugs That Affect the Heart, Blood Vessels, and Blood
CCBs relax peripheral arterioles and decrease afterload.
Second, verapamil and diltiazem reduce heart rate and
contractility (in addition to decreasing afterload).
CCBs relieve pain of variant angina by increasing cardiac
oxygen supply. The mechanism is relaxation of coronary
artery spasm.
When a CCB is combined with a beta blocker, a dihydropyridine (e.g., nifedipine) is preferred to verapamil or
diltiazem. Verapamil and diltiazem will intensify cardiosuppression caused by the beta blocker, whereas a dihydropyridine will not.
Ranolazine appears to reduce anginal pain by helping the
heart generate energy more efficiently.
Ranolazine should not be used alone. Rather, it should
be combined with a nitrate, a beta blocker, or the CCB
amlodipine.
Ranolazine increases the QT interval and may pose a risk
of torsades de pointes, a serious ventricular dysrhythmia.
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In patients with chronic stable angina, treatment has two
objectives: (1) prevention of MI and death and (2) prevention of anginal pain.
The risk of MI and death can be decreased with two types
of drugs: (1) antiplatelet agents (e.g., aspirin, clopidogrel)
and (2) cholesterol-lowering drugs.
Anginal pain is prevented with one or more long-acting
antianginal drugs (beta blocker, CCB, long-acting nitrate)
supplemented with sublingual nitroglycerin when breakthrough pain occurs.
As a rule, revascularization with CABG surgery or PCI is
indicated only after treatment with two or three antianginal
drugs has failed.
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Summary of Major Nursing Implicationsa
NITROGLYCERIN
Preadministration Assessment
Therapeutic Goal
Reduction of the frequency and intensity of anginal
attacks.
Baseline Data
Obtain baseline data on the frequency and intensity of anginal
attacks, the location of anginal pain, and the factors that
precipitate attacks.
The patient interview and physical examination should
identify risk factors for angina pectoris, including treatable
contributing pathophysiologic conditions (e.g., hypertension,
hyperlipidemia).
Identifying High-Risk Patients
Use with caution in hypotensive patients and in patients taking
drugs that can lower blood pressure, including alcohol and
antihypertensive medications. Use with sildenafil [Viagra]
and other PDE5 inhibitors is contraindicated.
Implementation: Administration
Routes and Administration
Sublingual Tablets or Powder
Use. Prophylaxis or termination of an acute anginal
attack.
Technique of Administration. Instruct patients to place
the tablet or empty the powder under the tongue and leave
it there until fully dissolved; these medications should not
be swallowed.
Instruct patients to call 911 or go to an emergency department if pain is not relieved in 5 minutes. While awaiting
emergency care, they can take 1 more dose, and then a third
5 minutes later.
Instruct patients to store tablets in a dry place at room
temperature in their original container, which should be closed
tightly after each use. Under these conditions, the tablets should
remain effective until the expiration date on the container.
Sustained-Release Oral Capsules
Use. Sustained protection against anginal attacks. To avoid
tolerance, administer only once or twice daily.
Technique of Administration. Instruct patients to
swallow these preparations intact, without chewing or
crushing.
Transdermal Delivery Systems
Use. Sustained protection against anginal attacks.
Technique of Administration. Instruct patients to apply
transdermal patches to a hairless area of skin, using a new
patch and a different site each day.
Instruct patients to remove the patch after 12 to 14 hours,
allowing 10 to 12 “patch-free” hours each day. This will
prevent tolerance.
Translingual Spray
Use. Prophylaxis or termination of an acute anginal attack.
Technique of Administration. Instruct patients to direct
the spray against the oral mucosa. Warn patients not to
inhale the spray.
Topical Ointment
Use. Sustained protection against anginal attacks. Instruct
patients to remove any remaining ointment before applying
a new dose.
Technique of Administration. (1) Squeeze a ribbon of
ointment of prescribed length onto the applicator paper
provided; (2) using the applicator paper, spread the ointment
over an area at least 2.5 inches by 3.5 inches (application
may be made to the chest, back, abdomen, upper arm, or
anterior thigh); and (3) cover the ointment with plastic wrap.
Avoid touching the ointment.
Instruct patients to rotate the application site to minimize
local irritation.
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CHAPTER 51
Drugs for Angina Pectoris
Summary of Major Nursing Implicationsa—cont’d
Intravenous
Uses. (1) Angina pectoris refractory to more conventional
therapy, (2) perioperative control of blood pressure, (3)
production of controlled hypotension during surgery, and (4)
heart failure associated with acute MI.
Technique of Administration. Infuse IV using a glass
IV bottle and the administration set provided by the manufacturer; avoid standard IV tubing. Check the stock solution
label to verify volume and concentration, which can differ
among manufacturers. Dilute stock solutions before use.
Administer by continuous infusion. The rate is slow initially
(5 mcg/min) and then gradually increased until an adequate
response is achieved.
Monitor cardiovascular status constantly.
Minimizing Adverse Effects
Headache. Inform patients that headache will diminish
with continued drug use. Advise patients that headache can
be relieved with aspirin, acetaminophen, or some other mild
analgesic.
Orthostatic Hypotension. Inform patients about symptoms of hypotension (e.g., dizziness, light-headedness), and
advise them to sit or lie down if these occur. Inform patients
that hypotension can be minimized by moving slowly when
changing from a sitting or supine position to an upright
posture.
Reflex Tachycardia. This reaction can be suppressed
by concurrent treatment with a beta blocker, verapamil, or
diltiazem.
Terminating Therapy
Minimizing Adverse Interactions
Warn patients against abrupt withdrawal of long-acting
preparations (transdermal systems, topical ointment, sustainedrelease tablets and capsules).
Hypotensive Agents, Including PDE5 Inhibitors. Nitroglycerin can interact with other hypotensive drugs to produce
excessive lowering of blood pressure. Advise patients to
avoid alcohol. Exercise caution when nitroglycerin is used
in combination with beta blockers, calcium channel blockers,
diuretics, and all other drugs that can lower blood pressure.
Implementation: Measures to Enhance
Therapeutic Effects
Reducing Risk Factors
Precipitating Factors. Advise patients to avoid activities
that are likely to elicit an anginal attack (e.g., overexertion,
heavy meals, emotional stress, cold exposure).
Exercise. Encourage patients who have a sedentary
lifestyle to establish a regular program of aerobic exercise
(e.g., walking, jogging, swimming, biking).
Smoking Cessation. Strongly encourage patients to quit
smoking.
Contributing Disease States. Ensure that patients with
contributing pathology (especially hypertension or hypercholesterolemia) are receiving appropriate treatment.
Warn patients not to combine nitroglycerin with a PDE5
inhibitor (e.g., sildenafil [Viagra]), because life-threatening
hypotension can result.
ISOSORBIDE MONONITRATE AND
ISOSORBIDE DINITRATE
Both drugs have pharmacologic actions identical to those of
nitroglycerin. Differences relate only to dosage forms, routes
of administration, and time course of action. Therefore, the
implications presented for nitroglycerin apply to these drugs
as well.
Ongoing Evaluation and Interventions
Evaluating Therapeutic Effects
Instruct patients to keep a record of the frequency and
intensity of anginal attacks, the location of anginal pain, and
the factors that precipitate attacks.
Patient education information is highlighted as blue text.
a
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UNIT VII
Drugs That Affect the Heart, Blood Vessels, and Blood
with respect to mortality (6.2% with each drug), ICH (0.93%
with tenecteplase vs. 0.94% with tPA), and total stroke (1.78%
vs. 1.66% with tPA). Of significance, the incidence of major
hemorrhage (other than intracranial) was lower with tenecteplase
(4.7% vs. 5.9%).
Tenecteplase dosage is based on body weight as follows:
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•
Below 60 kg: dose 30 mg
60 to 69.9 kg: dose 35 mg
70 to 79.9 kg: dose 40 mg
80 to 89.9 kg: dose 45 mg
Above 90 kg: dose 50 mg
Reteplase
Reteplase [Retavase] is a derivative of tPA produced by recombinant DNA
technology. In contrast to tPA itself, which contains 527 amino acids, reteplase
is composed of only 355 amino acids. Like tPA, reteplase converts plasminogen
to plasmin, which in turn digests the fibrin matrix of the thrombus. Reteplase
has a short half-life (13 to 16 minutes), owing to rapid clearance by the liver
and kidneys. As with other thrombolytic drugs, bleeding is the major adverse
effect. The risk of bleeding is increased by concurrent use of heparin, aspirin,
and other drugs that impair hemostasis.
Reteplase is approved only for acute MI. Treatment consists of two 10-unit
doses separated by 30 minutes. Each dose is given by IV bolus injected over
a 2-minute interval. Reteplase should not be administered through a line that
contains heparin. If a heparin-containing line must be used, it should be
flushed before giving reteplase.
KEY POINTS
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Hemostasis occurs in two stages: formation of a platelet
plug, followed by coagulation (i.e., production of fibrin,
a protein that reinforces the platelet plug).
Platelet aggregation depends on activation of platelet
glycoprotein (GP) IIb/IIIa receptors, which bind fibrinogen
to form cross-links between platelets.
Fibrin is produced by two pathways—the contact activation
pathway (aka intrinsic pathway) and the tissue factor
pathway (aka extrinsic pathway)—that converge at clotting
factor Xa, which catalyzes formation of thrombin, which
in turn catalyzes formation of fibrin.
Four factors in the coagulation pathways require an activated
form of vitamin K for their synthesis.
Plasmin, the active form of plasminogen, serves to degrade
the fibrin meshwork of clots.
A thrombus is a blood clot formed within a blood vessel
or the atria of the heart.
Arterial thrombi begin with formation of a platelet plug,
which is then reinforced with fibrin.
Venous thrombi begin with formation of fibrin, which then
enmeshes red blood cells and platelets.
Arterial thrombi are best prevented with antiplatelet drugs
(e.g., aspirin, clopidogrel), whereas venous thrombi are
best prevented with anticoagulants (e.g., heparin, warfarin,
dabigatran).
Heparin is a large polymer (molecular weight range, 3000
to 30,000) that carries many negative charges.
Heparin suppresses coagulation by helping antithrombin
inactivate thrombin and factor Xa.
Heparin is administered IV or subQ. Because of its large
size and negative charges, heparin is unable to cross
membranes, and hence cannot be administered PO.
Anticoagulant effects of heparin develop within minutes
of IV administration.
The major adverse effect of heparin is bleeding.
Severe heparin-induced bleeding can be treated with
protamine sulfate, a drug that binds heparin and thereby
stops it from working.
Heparin-induced thrombocytopenia is a potentially fatal
condition caused by development of antibodies against
heparin–platelet protein complexes.
Heparin is contraindicated for patients with thrombocytopenia or uncontrollable bleeding, and must be used with
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628
extreme caution in all patients for whom there is a high
likelihood of bleeding.
Heparin therapy is monitored by measuring the activated
partial thromboplastin time (aPTT) or anti-Xa heparin assay.
The target aPTT is 60 to 80 seconds (i.e., 1.5 to 2 times
the normal value of 40 seconds). The target anti-Xa level
is 0.3 to 0.7 IU/mL.
Low-molecular-weight (LMW) heparins are produced by
breaking molecules of unfractionated heparin into smaller
pieces.
In contrast to unfractionated heparin, which inactivates
factor Xa and thrombin equally, LMW heparins preferentially inactivate factor Xa.
In contrast to unfractionated heparin, LMW heparins do
not bind nonspecifically to plasma proteins and tissues.
As a result, their bioavailability is high, making their plasma
levels predictable.
Because plasma levels of LMW heparins are predictable,
these drugs can be administered using a fixed dosage, with
no need for routine laboratory monitoring. As a result,
LMW heparins can be used at home.
Warfarin is our oldest oral anticoagulant.
Warfarin prevents the activation of vitamin K and thereby
blocks the biosynthesis of vitamin K–dependent clotting
factors.
Anticoagulant responses to warfarin develop slowly and
persist for several days after warfarin is discontinued.
Warfarin is used to prevent venous thromboembolism (VTE)
and to prevent stroke and systemic embolism in patients
with atrial fibrillation.
Warfarin therapy is monitored by measuring prothrombin
time (PT). Results are expressed as an international normalized ratio (INR). An INR of 2 to 3 is the target for most
patients.
Bleeding is the major complication of warfarin therapy.
Genetic testing for variant genes that code for VKORC1 and
CYP2C9 can identify people with increased sensitivity to
warfarin, and who therefore may need a dosage reduction.
Moderate warfarin overdose is treated with vitamin K.
Warfarin must not be used during pregnancy. The drug can
cause fetal malformation, CNS defects, and optic atrophy.
Warfarin is subject to a large number of clinically significant
drug interactions. Drugs can increase anticoagulant effects
CHAPTER 52
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by displacing warfarin from plasma albumin, by inhibiting
hepatic enzymes that degrade warfarin, and by decreasing
synthesis of clotting factors. Drugs can decrease anticoagulant effects by inducing hepatic drug-metabolizing enzymes,
increasing synthesis of clotting factors, and inhibiting
warfarin absorption. Drugs that promote bleeding, such
as heparin and aspirin, will obviously increase the risk of
bleeding in patients taking warfarin. Instruct patients to
avoid all drugs—prescription and nonprescription—that
have not been specifically approved by the prescriber.
Dabigatran is an oral anticoagulant that works by direct
inhibition of thrombin.
Dabigatran is an alternative to warfarin for chronic anticoagulation in patients with atrial fibrillation.
Compared with warfarin, dabigatran has five advantages:
rapid onset, fixed dosage, no need for coagulation testing,
few drug-food interactions, and a lower risk of hemorrhagic
stroke and other major bleeds.
Compared with warfarin, dabigatran has three disadvantages: no antidote, limited clinical experience, and more
GI disturbances (dyspepsia, ulceration, gastritis, etc.).
Rivaroxaban, edoxaban, and apixaban are oral anticoagulants that work by direct inhibition of factor Xa.
Like dabigatran, rivaroxaban, edoxaban, and apixaban are
safer than warfarin and easier to use.
Aspirin and other antiplatelet drugs suppress thrombus
formation in arteries.
Aspirin inhibits platelet aggregation by causing irreversible
inhibition of cyclooxygenase. Since platelets are unable
to synthesize new cyclooxygenase, inhibition persists for
the life of the platelet (7 to 10 days).
In its role as an antiplatelet drug, aspirin is given for multiple
purposes, including primary prevention of myocardial
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Anticoagulant, Antiplatelet, and Thrombolytic Drugs
infarction (MI), acute management of MI, and reduction
of cardiovascular events in patients with unstable angina,
chronic stable angina, ischemic stroke, or a history of
transient ischemic attacks (TIAs).
When used to suppress platelet aggregation, aspirin is
administered in low doses—typically 80 to 325 mg/day.
Clopidogrel suppresses platelet aggregation by causing
irreversible blockade of P2Y12 ADP receptors on the platelet
surface.
Clopidogrel is a prodrug that undergoes conversion to its
active form by hepatic CYP2C19.
Patients with an inherited deficiency in CYP2C19 may
have an unreliable response to clopidogrel.
The major adverse effect of clopidogrel is bleeding.
The GP IIb/IIIa receptor blockers (e.g., abciximab) inhibit
the final common step in platelet aggregation, and hence
are the most effective antiplatelet drugs available.
Alteplase (tPA) and other thrombolytic drugs (aka fibrinolytic drugs) are used to dissolve existing thrombi (rather
than prevent thrombi from forming).
Thrombolytic drugs work by converting plasminogen to
plasmin, an enzyme that degrades the fibrin matrix of
thrombi.
Thrombolytic therapy is most effective when started early
(e.g., for acute MI, within 4 to 6 hours of symptom onset,
and preferably sooner).
Thrombolytic drugs carry a significant risk of bleeding.
Intracranial hemorrhage is the greatest concern.
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Summary of Major Nursing Implicationsa
HEPARIN
Preadministration Assessment
Therapeutic Goal
The objective is to prevent thrombosis without inducing
spontaneous bleeding.
Heparin is the preferred anticoagulant for use during
pregnancy and in situations that require rapid onset of effects,
including PE, evolving stroke, and massive DVT. Other
indications include open heart surgery, renal dialysis, and
disseminated intravascular coagulation. Low doses are used
to prevent postoperative venous thrombosis and to enhance
thrombolytic therapy of MI.
Baseline Data
Obtain baseline values for blood pressure, heart rate, complete
blood cell counts, platelet counts, hematocrit, and aPTT.
Identifying High-Risk Patients
Heparin is contraindicated for patients with severe thrombocytopenia or uncontrollable bleeding and for patients undergoing
lumbar puncture, regional anesthesia, or surgery of the eye,
brain, or spinal cord.
Use with extreme caution in patients at high risk of bleeding, including those with hemophilia, increased capillary
permeability, dissecting aneurysm, GI ulcers, or severe
hypertension. Caution is also needed in patients with severe
hepatic or renal impairment.
Implementation: Administration
Routes
Intravenous (continuous infusion or intermittent) and subQ.
Avoid IM injections!
Administration
General Considerations. Dosage is prescribed in units,
not milligrams. Heparin preparations vary widely in concentration; read the label carefully to ensure correct dosing.
Continuous IV Infusion. Administer with a continuous
infusion pump or some other approved volume-control unit.
Policy may require that dosage be double-checked by a second
person. Check the infusion rate every 30 to 60 minutes. During
Continued
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Summary of Major Nursing Implicationsa—cont’d
the early phase of treatment, the aPTT or anti-Xa level should
be determined every 6 hours. Check the site of needle insertion
periodically for extravasation.
Ongoing Evaluation and Interventions
Evaluating Treatment
We evaluate treatment by measuring the aPTT or the anti-Xa
level. Heparin should increase the aPTT by 1.5- to 2-fold
above baseline. Therapeutic range for anti-Xa level is 0.3 to
0.7 IU/mL.
Minimizing Adverse Effects
Hemorrhage. Heparin overdose may cause hemorrhage.
Monitor closely for signs of bleeding. These include reduced
blood pressure, elevated heart rate, discolored urine or stool,
bruises, petechiae, hematomas, persistent headache or faintness
(suggestive of cerebral hemorrhage), pelvic pain (suggestive of
ovarian hemorrhage), and lumbar pain (suggestive of adrenal
hemorrhage). Laboratory data suggesting hemorrhage include
reductions in the hematocrit and blood cell counts. If bleeding
occurs, heparin should be discontinued. Severe overdose can
be treated with protamine sulfate administered by slow IV
injection. The risk of bleeding can be reduced by ensuring that
the aPTT or the anti-Xa levels are not above recommended
range according to facility protocol.
Heparin-Induced Thrombocytopenia. HIT, characterized by reduced platelet counts and increased thrombotic
events, poses a risk of DVT, PE, cerebral thrombosis, MI,
and ischemic injury to the arms and legs. To reduce risk,
monitor platelet counts 2 to 3 times a week during the first
3 weeks of heparin use, and monthly thereafter. If severe
thrombocytopenia develops (platelet count below 100,000/
mm3), discontinue heparin and, if anticoagulation is still
needed, substitute another anticoagulant, such as argatroban.
Spinal/Epidural Hematoma. Heparin and all other
anticoagulants pose a risk of spinal or epidural hematoma
in patients undergoing spinal puncture or spinal/epidural
anesthesia. Prolonged or permanent paralysis can result. Risk
of hematoma is increased by several factors, including use of
an indwelling epidural catheter, use of other anticoagulants
(e.g., warfarin, dabigatran), and use of antiplatelet drugs (e.g.,
aspirin, clopidogrel). Monitor for signs and symptoms of
neurologic impairment. If impairment develops, immediate
intervention is needed.
Hypersensitivity Reactions. Allergy may develop to
antigens in heparin preparations. To minimize the risk of
severe reactions, administer a small test dose before the full
therapeutic dose.
Minimizing Adverse Interactions
Antiplatelet Drugs. Concurrent use of aspirin, clopidogrel, and other antiplatelet drugs increases the risk of bleeding.
Use these agents with caution.
WARFARIN, A VITAMIN K ANTAGONIST
Preadministration Assessment
Therapeutic Goal
The goal is to prevent thrombosis without inducing spontaneous bleeding. Specific indications include prevention of venous
thrombosis and associated PE, prevention of thromboembolism
in patients with prosthetic heart valves, and prevention of
stroke and systemic embolism in patients with atrial fibrillation.
Baseline Data
Obtain a thorough medical history. Be sure to identify use of
any medications that might interact adversely with warfarin.
Obtain baseline values of vital signs and PT. Genetic testing
for variants of CYP2C9 and VKORC1 may be done to
identify patients who may require a reduction in warfarin
dosage.
Identifying High-Risk Patients
Warfarin is contraindicated in the presence of vitamin K
deficiency, liver disease, alcoholism, thrombocytopenia,
uncontrollable bleeding, pregnancy, and lactation, and for
patients undergoing lumbar puncture, regional anesthesia, or
surgery of the eye, brain, or spinal cord.
Use with extreme caution in patients at high risk of bleeding, including those with hemophilia, increased capillary
permeability, dissecting aneurysm, GI ulcers, and severe
hypertension.
Use with caution in patients with variant forms of CYP2C9
or VKORC1.
Implementation: Administration
Route
Oral.
Administration
For most patients, dosage is adjusted to maintain an INR
value of 2 to 3. Maintain a flow chart for hospitalized patients
indicating INR values, dose, and administration time.
Implementation: Measures to Enhance
Therapeutic Effects
Promoting Adherence
Safe and effective therapy requires rigid adherence to the
dosing schedule. Achieving adherence requires active and
informed participation by the patient. Provide the patient
with detailed written and verbal instructions regarding the
purpose of treatment, dosage size and timing, and the
importance of careful adherence to the dosing schedule. Also,
provide the patient with a chart on which to keep an ongoing
record of warfarin use. If the patient is incompetent (e.g.,
mentally ill, alcoholic, senile), ensure that a responsible
individual supervises treatment.
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Anticoagulant, Antiplatelet, and Thrombolytic Drugs
Summary of Major Nursing Implicationsa—cont’d
Nondrug Measures
Advise the patient to (1) avoid prolonged immobility, (2)
elevate the legs when sitting, (3) avoid garments that can
restrict blood flow in the legs, (4) participate in exercise
activities, and (5) wear support hose. These measures will
reduce venous stasis and will thereby reduce the risk of
thrombosis.
Ongoing Evaluation and Interventions
Monitoring Treatment
Evaluate therapy by monitoring PT. Test results are reported
as an international normalized ratio (INR). For most patients,
the target INR is 2 to 3. If the INR is below this range, dosage
should be increased. Conversely, if the INR is above this
range, dosage should be reduced.
The INR should be determined frequently: daily during
the first 5 days, twice a week for the next 1 to 2 weeks, once
a week for the next 1 to 2 months, and every 2 to 4 weeks
thereafter. In addition, the INR should be determined whenever
a drug that interacts with warfarin is added to or withdrawn
from the regimen.
When appropriate, teach patients how to monitor their
PT and INR at home.
Minimizing Adverse Effects
Hemorrhage. Hemorrhage is the major complication of
warfarin therapy. Warn patients about the danger of hemorrhage, and inform them about signs of bleeding. These include
reduced blood pressure, elevated heart rate, discolored urine
or stools, bruises, petechiae, hematomas, persistent headache
or faintness (suggestive of cerebral hemorrhage), pelvic pain
(suggestive of ovarian hemorrhage), and lumbar pain (suggestive of adrenal hemorrhage). Laboratory data suggesting
hemorrhage include reductions in the hematocrit and blood
cell counts.
Instruct the patient to withhold warfarin and notify the
prescriber if signs of bleeding are noted. Advise the patient
to wear some form of identification (e.g., Medic Alert bracelet)
to alert emergency personnel to warfarin use.
To reduce the incidence of bleeding, advise the patient
to avoid excessive consumption of alcohol. Suggest use of
a soft toothbrush to prevent bleeding from the gums. Advise
patients to shave with an electric razor.
Warfarin intensifies bleeding during surgical procedures.
Instruct the patient to make certain the surgeon is aware of
warfarin use. Warfarin should be discontinued several days
before elective procedures. If emergency surgery must be
performed, vitamin K1 can help reduce bleeding.
Warfarin-induced bleeding can be controlled with vitamin
K1. For most patients, oral vitamin K will suffice. For patients
with severe bleeding or a very high INR, vitamin K is given
by injection (usually IV).
Use in Pregnancy and Lactation. Warfarin can cross
the placenta, causing fetal hemorrhage and malformation.
Inform those of childbearing age about potential risks to the
fetus, and warn them against becoming pregnant. If pregnancy
develops, termination should be considered.
Warfarin enters breast milk and may harm the nursing
infant. Warn patients against breast-feeding.
Minimizing Adverse Interactions
Inform patients that warfarin is subject to a large number
of potentially dangerous drug interactions. Instruct them to
avoid all drugs—prescription and nonprescription—that have
not been specifically approved by the prescriber. Before
treatment, take a complete medication history to identify any
drugs that might interact adversely with warfarin.
CLOPIDOGREL, A P2Y12 ADENOSINE
DIPHOSPHATE RECEPTOR ANTAGONIST
Preadministration Assessment
Therapeutic Goal
Clopidogrel is used to prevent blockage of coronary artery
stents and to reduce thrombotic events—MI, ischemic stroke,
and vascular death—in patients with ACS and in those with
atherosclerosis documented by recent MI, recent stroke, or
established peripheral arterial disease.
Baseline Data
Consider testing for variants of the CYP2C19 gene to
determine whether the patient is a poor metabolizer of
clopidogrel.
Identifying High-Risk Patients
Clopidogrel is contraindicated in patients with active pathologic bleeding, including ICH and bleeding ulcers. Use with
caution in patients taking other drugs that promote bleeding.
Generally avoid clopidogrel in poor metabolizers of the drug.
Implementation: Administration
Route
Oral.
Administration
Instruct patients to take clopidogrel once a day, with or
without food.
Ongoing Evaluation and Interventions
Promoting Beneficial Effects
Instruct patients being treated for ACS to take aspirin (75 to
325 mg) once daily.
Minimizing Adverse Effects
Bleeding. Clopidogrel poses a risk of serious bleeding.
Avoid clopidogrel in patients with active pathologic bleeding,
and use with caution in patients taking other drugs that promote
bleeding. If possible, manage major bleeding without stopping
clopidogrel, since discontinuation would increase the risk of
a thrombotic event.
Inform patients about the risk of bleeding, and warn them
that:
• You may bruise more easily.
• You may bleed more easily.
Continued
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Summary of Major Nursing Implicationsa—cont’d
• You are more likely to get nosebleeds.
• Bleeding will take longer than usual to stop.
Instruct patients to contact the prescriber if they experience
any of these symptoms of bleeding:
• Unexpected bleeding
• Bleeding that lasts a long time
• Blood in the urine, indicated by discoloration (pink, red,
brown)
• Blood in stools (indicated by red, black, tarry stools)
• Bruising with no obvious cause
• Vomiting blood, which may look like coffee grounds
Instruct patients that, even if these symptoms occur, they
should continue taking clopidogrel until the prescriber says
they should stop.
Instruct patients to discontinue clopidogrel 5 days before
elective surgery.
Thrombotic Thrombocytopenic Purpura (TTP). Rarely,
patients develop TTP, a potentially fatal condition characterized by thrombocytopenia, hemolytic anemia, neurologic
symptoms, renal dysfunction, and fever. If TTP is diagnosed,
urgent treatment—including plasmapheresis—is required.
Minimizing Adverse Interactions
Drugs That Promote Bleeding. Use with caution in
patients taking other drugs that promote bleeding (e.g., heparin,
warfarin, dabigatran, aspirin, and nonaspirin NSAIDs).
Proton Pump Inhibitors (PPIs). The PPIs can help prevent
clopidogrel-related GI bleeding—but may reduce the benefits
of clopidogrel by inhibiting CYP2C19, the hepatic enzyme
that converts clopidogrel to its active form. In patients with
risk factors for GI bleeding (e.g., advanced age, use of NSAIDs
or anticoagulants), the benefits of combining a PPI with
clopidogrel probably outweigh any risk from reduced antiplatelet effects. Conversely, in patients who lack risk factors
for GI bleeding, combined use of clopidogrel with a PPI may
reduce the benefits of clopidogrel without offering any
meaningful GI protection—and hence combining a PPI with
clopidogrel in these patients should probably be avoided.
When a PPI is used with clopidogrel, pantoprazole is a good
choice because, compared with other PPIs, pantoprazole
causes less inhibition of CYP2C19.
CYP2C19 Inhibitors (Other Than PPIs). Like the PPIs,
several other drugs can inhibit CYP2C19. Among these are
cimetidine, fluoxetine, fluvoxamine, fluconazole, ketoconazole,
voriconazole, etravirine, felbamate, and ticlopidine. Since
these drugs may reduce the antiplatelet effects of clopidogrel,
using an alternative to these drugs is preferred.
Preadministration Assessment
Therapeutic Goal
All three thrombolytic drugs are used for acute MI, and one
drug—alteplase—is also used for ischemic stroke and PE, and,
in low dosage, for clearing blocked central venous catheters.
Baseline Data
Obtain baseline values for blood pressure, heart rate, platelet
counts, hematocrit, aPTT, PT, and fibrinogen level.
Identifying High-Risk Patients
Thrombolytic drugs are contraindicated for patients with
active bleeding, aortic dissection, acute pericarditis, cerebral
neoplasm, cerebrovascular disease, or a history of intracranial
bleeding.
Use with great caution in patients with relative contraindications, including pregnancy, severe hypertension, ischemic
stroke within the prior 6 months, and major surgery within
the prior 2 to 4 weeks. See Table 52.10 for other absolute
and relative contraindications.
Implementation: Administration
Route
Intravenous.
Administration (for Acute MI)
Alteplase. Administer as an initial IV bolus followed by
a 90-minute IV infusion.
Tenecteplase. Administer as a single IV bolus.
Reteplase. Administer as two IV boluses, separated by
30 minutes.
Ongoing Evaluation and Interventions
Minimizing Adverse Effects
Hemorrhage. Thrombolytics may cause bleeding; ICH
is the greatest concern. To reduce the risk of major bleeding,
minimize manipulation of the patient, avoid subQ and IM
injections, minimize invasive procedures, and minimize
concurrent use of anticoagulants and antiplatelet drugs.
Manage oozing at cutaneous puncture sites with a pressure
dressing.
Minimizing Adverse Interactions
Anticoagulants and Antiplatelet Drugs. Anticoagulants
(e.g., heparin, warfarin, dabigatran) and antiplatelet drugs
(e.g., aspirin, clopidogrel) increase the risk of bleeding from
antithrombotics. Avoid high-dose therapy with these drugs
until thrombolytic effects have subsided.
THROMBOLYTIC (FIBRINOLYTIC) DRUGS
Alteplase (tPA)
Reteplase
Tenecteplase
Patient education information is highlighted as blue text.
a
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Ventricular Dysrhythmias
These dysrhythmias develop frequently and are the major cause
of death following MI. Sudden death from dysrhythmias occurs
in 15% of patients during the first hour. Ultimately, ventricular
dysrhythmias cause 60% of infarction-related deaths. Acute
management of ventricular fibrillation consists of defibrillation
followed by IV amiodarone for 24 to 48 hours. Programmed
ventricular stimulation with guided antidysrhythmic therapy
may be lifesaving for some patients.
Attempts to prevent dysrhythmias by giving antidysrhythmic
drugs prophylactically have failed to reduce mortality. Worse
yet, attempted prophylaxis of ventricular dysrhythmias with
two drugs—encainide and flecainide—actually increased
mortality. Similarly, when quinidine was employed to prevent
supraventricular dysrhythmias, it too increased mortality.
Therefore, since prophylaxis with antidysrhythmic drugs does
not reduce mortality—and may in fact increase mortality—
antidysrhythmic drugs should be withheld until a dysrhythmia
actually occurs.
Cardiogenic Shock
Shock results from greatly reduced tissue perfusion secondary
to impaired cardiac function. Shock develops in 7% to 10% of
patients in the first few days after MI and has a mortality rate
of up to 50% in hospitalized patients. Patients at highest risk
are those with large infarcts, a previous infarct, a low ejection
fraction (less than 35%), diabetes, and advanced age. Drug
therapy includes inotropic agents (e.g., dopamine, dobutamine)
to increase cardiac output and vasodilators (nitroglycerin,
nitroprusside) to improve tissue perfusion and to reduce cardiac
work and oxygen demand. Unfortunately, although these drugs
can improve hemodynamic status, they do not seem to reduce
mortality. Restoration of cardiac perfusion with PCI or coronary
artery bypass grafting may be of value.
Heart Failure
Heart failure secondary to acute MI can be treated with a
combination of drugs. A diuretic (e.g., furosemide) is given
to decrease preload and pulmonary congestion. Inotropic
agents (e.g., digoxin) increase cardiac output by enhancing
contractility. Vasodilators (e.g., nitroglycerin, nitroprusside)
improve hemodynamic status by reducing preload, afterload,
or both. ACE inhibitors (or ARBs), which reduce both preload
and afterload, can be especially helpful. Beta blockers may also
improve outcome. Drug therapy of heart failure is discussed
in Chapter 48.
Cardiac Rupture
Weakening of the myocardium predisposes the heart wall to
rupture. Following rupture, shock and circulatory collapse
develop rapidly. Death is often immediate. Fortunately, cardiac
rupture is relatively rare (less than 2% incidence). Patients at
highest risk are those with a large anterior infarction. Cardiac
rupture is most likely within the first days after MI. Early
treatment with vasodilators and beta blockers may reduce the
risk of wall rupture.
SECONDARY PREVENTION OF STEMI
As a rule, patients who survive the acute phase of STEMI can
be discharged from the hospital as early as 72 hours after
admission if they remain free of complications. However, they
are still at risk of reinfarction (5% to 15% incidence within
the first year) and other complications (e.g., dysrhythmias,
heart failure). Outcome can be improved with risk factor
reduction, exercise, and long-term therapy with drugs.
Reduction of risk factors for MI can increase long-term
survival. Patients who smoke must be encouraged to quit; the
goal is total cessation. Patients with high serum cholesterol
should be given an appropriate dietary plan and, if necessary,
treated with a high-dose statin. Hypertension and diabetes
increase the risk of mortality and must be controlled. For patients
with hypertension, blood pressure should be decreased to below
140/90 mm Hg. For patients with diabetes, the goal is a level
of hemoglobin A1C below 7%.
Exercise training can be valuable for two reasons: it reduces
complications associated with prolonged bed rest and it accelerates return to an optimal level of functioning. The goal is 30
minutes of exercise at least 3 to 4 days a week. Although
exercise is safe for most patients, there is concern about cardiac
risk and impairment of infarct healing in patients whose infarct
is large.
All post-MI patients should take four drugs: (1) a beta
blocker; (2) an ACE inhibitor or an ARB; either (3a) an
antiplatelet drug (aspirin or clopidogrel, ticagrelor, or prasugrel)
or (3b) an anticoagulant (warfarin); and (4) a statin. All four
should be taken indefinitely.
Estrogen therapy for postmenopausal women is not effective
as secondary prevention and should not be initiated.
KEY POINTS
■
■
MI is necrosis of the myocardium secondary to acute
occlusion of a coronary artery. The usual cause is platelet
plugging and thrombus formation at the site of a ruptured
atherosclerotic plaque.
STEMI is diagnosed by the presence of chest pain, characteristic ECG changes, and elevated serum levels of cardiac
troponins.
■
638
Aspirin suppresses platelet aggregation, decreasing mortality, reinfarction, and stroke. All patients should chew a
162- to 325-mg dose on hospital admission and should
take 81 to 162 mg/day indefinitely after discharge. In
patients undergoing acute STEMI, beta blockers reduce
cardiac pain, infarct size, short-term mortality, recurrent
ischemia, and reinfarction. Continued use increases
CHAPTER 53
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■
long-term survival. All patients should receive a beta blocker
in the absence of specific contraindications.
Oxygen, morphine, and nitroglycerin are considered routine
therapy for suspected STEMI. They should be started, as
appropriate, soon after symptom onset.
Reperfusion therapy, which restores blood flow through
blocked coronary arteries, is the most beneficial treatment
for STEMI.
Reperfusion can be accomplished with PCI or with fibrinolytic drugs. Both approaches are highly effective, but
PCI is now generally preferred.
PCI usually consists of balloon angioplasty coupled with
placement of a drug-eluting stent.
Fibrinolytic drugs dissolve clots by converting plasminogen
into plasmin, an enzyme that digests the fibrin meshwork
that holds clots together.
Typically, all fibrinolytic drugs are equally effective.
However, when treatment is initiated within 4 to 6 hours
of pain onset, alteplase is most effective.
The major complication of fibrinolytic therapy is bleeding.
Intracranial hemorrhage is the greatest concern.
Heparin is recommended for all patients undergoing
fibrinolytic therapy or PCI.
■
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Management of ST-Elevation Myocardial Infarction
Aspirin (an antiplatelet drug) combined with clopidogrel
is recommended for all patients undergoing reperfusion
therapy with a fibrinolytic drug.
Glycoprotein IIb/IIIa inhibitors (e.g., abciximab) are
powerful IV antiplatelet drugs that can enhance the benefits
of primary PCI.
In patients with acute MI, ACE inhibitors decrease mortality,
severe heart failure, and recurrent MI. All patients should
receive an ACE inhibitor in the absence of specific contraindications. For patients who cannot tolerate ACE
inhibitors, an ARB may be used instead.
To lower the risk of a second MI, all patients should decrease
cardiovascular risk factors (e.g., smoking, hypercholesterolemia, hypertension, diabetes), exercise for 30 minutes
at least 3 or 4 days a week, and undergo long-term therapy
with four drugs: a beta blocker, an ACE inhibitor or an
ARB, an antiplatelet drug or warfarin, and a statin.
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KEY POINTS
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■
Hemophilia is a bleeding disorder seen almost exclusively
in males. The underlying cause is a genetically based
deficiency of clotting factors.
Hemophilia has two forms: hemophilia A (factor VIII
deficiency) and hemophilia B (factor IX deficiency).
Hemophilia may be severe, moderate, or mild, depending
on the degree of clotting factor deficiency.
Patients with severe hemophilia may experience lifethreatening hemorrhage in response to minor trauma,
whereas those with mild hemophilia may experience little
or no excessive bleeding.
Repeated bleeding in the knee and other joints can cause
permanent joint damage.
The cornerstone of hemophilia treatment is replacement
therapy with factor VIII (hemophilia A) or factor IX
(hemophilia B).
Replacement therapy may be done prophylactically (to
prevent bleeding and thus prevent joint injury) or on demand
(to stop an ongoing bleed or to prevent excessive bleeding
during surgery).
Clotting factor products are made in two basic ways:
extraction from donor plasma and production in cell culture
using recombinant DNA technology.
All clotting factor concentrates, whether plasma derived
or recombinant, are equally effective.
All clotting factor concentrates in use today are very safe:
They carry no risk of transmitting HIV/AIDS and little or
no risk of transmitting hepatis or CJD. However, because
recombinant factors are, in theory, slightly safer than
plasma-derived factors, recombinant factors are considered
the treatment of choice.
As a rule, clotting factors are given by slow IV push.
Continuous infusion may also be done, but only by a clinician with special training.
Clotting factor dosage depends primarily on the site and
severity of the bleed.
A dose of 1 unit of factor VIII/kg will raise the plasma
level of factor VIII activity by 2%, whereas 1 unit of factor
IX/kg will raise the plasma level of factor IX activity by
only 1%.
■
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■
Although we can monitor the activity of clotting factors
in blood to help guide treatment, dosage is ultimately
determined by the clinical response.
For prophylaxis, clotting factor concentrates are administered on a regular schedule, usually every other day to 3
times a week for factor VIII and twice a week for factor
IX. With both factors, the goal is to maintain plasma factor
levels above 1% of normal.
To facilitate frequent IV administration during prophylaxis,
a central venous access device can be installed.
Clotting factor concentrates can cause allergic reactions.
Mild reactions can be managed with an antihistamine (e.g.,
diphenhydramine [Benadryl]). The most severe reaction—
anaphylaxis—is treated with subQ epinephrine.
For some patients with mild hemophilia A, bleeding can
be stopped with desmopressin, a drug that promotes the
release of stored factor VIII. Desmopressin does not release
factor IX, and so cannot treat hemophilia B.
Two drugs—aminocaproic acid and tranexamic acid—can
suppress fibrinolysis and can promote hemostasis in
hemophilia A and hemophilia B. These antifibrinolytic
agents are more effective for preventing recurrent bleeding
than for stopping an ongoing bleed.
Development of inhibitors (antibodies that neutralize factor
VIII or factor IX) is a serious complication of hemophilia
therapy.
Activated factor VII (factor VIIa) and AICC are preferred
agents for controlling bleeding when inhibitors of factor
VIII or factor IX are present.
People with hemophilia should avoid aspirin and other
traditional NSAIDs because these agents suppress platelet
aggregation and promote GI ulceration and bleeding.
Second-generation NSAIDs (COX-2 inhibitors) are probably
safe.
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Summary of Major Nursing Implicationsa
FACTOR VIII AND FACTOR IX CONCENTRATES
Preadministration Assessment
Therapeutic Goal
Factor VIII is indicated for replacement therapy in patients
with hemophilia A, and factor IX is indicated for replacement
therapy in patients with hemophilia B.
Both factors may be given prophylactically (to prevent
bleeding and subsequent joint injury) or “on demand” (to
stop ongoing bleeding or prevent excessive bleeding during
anticipated surgery).
Baseline Data
Obtain a baseline level for activity of factor VIII or factor IX.
Identifying High-Risk Patients
Use with caution in patients with a history of allergic reactions
to the factor concentrate.
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CHAPTER 54
Drugs for Hemophilia
Summary of Major Nursing Implicationsa—cont’d
therapy). With both forms of therapy, monitoring activity
levels of factor VIII or factor IX can help guide treatment.
Implementation: Administration
Route
Intravenous.
Administration
Administer by slow IV push or continuous infusion.
Record the following each time you give a factor
concentrate:
•
•
•
•
Time and date
Infusion site and rate
Total dose
Manufacturer, brand name, lot number, and expiration
date of the factor concentrate
Teach home caregivers about:
• The importance of having an assistant, who can give aid
•
•
•
•
•
•
or call for help if complications arise
The importance and proper method of hand washing
Making dosage calculations
Reconstituting the powdered factor concentrate
Infusion technique
Cleanup and waste disposal
Recording the time, date, and other information listed in
this section
Minimizing Adverse Effects
Allergic Reactions. Clotting factor concentrates can cause
allergic reactions, ranging from mild to severe. Inform patients
about symptoms of mild reactions (e.g., hives, rash, urticaria,
stuffy nose, fever), and advise them to take an antihistamine
(e.g., diphenhydramine) if these occur. Inform patients about
symptoms of anaphylaxis (wheezing, tightness in the throat,
shortness of breath, swelling in the face), and instruct them
to seek immediate emergency care if these develop. The
treatment of choice is epinephrine, injected subQ.
Minimizing Adverse Interactions
Aspirin. Warn patients not to use aspirin, a drug that
inhibits platelet aggregation and can cause GI ulceration and
bleeding.
NSAIDs Other Than Aspirin. Advise patients that firstgeneration NSAIDs (e.g., ibuprofen, naproxen) have actions
similar to those of aspirin, and hence should be avoided.
Advise patients that second-generation NSAIDs (e.g.,
celecoxib), which do not inhibit platelets and cause minimal
GI effects, are probably safe.
Ongoing Evaluation and Interventions
Evaluating Therapeutic Effects
Success is indicated by preventing bleeding (during prophylactic therapy) or controlling bleeding (during on-demand
Patient education information is highlighted as blue text.
a
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KEY POINTS
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The principal cause of iron deficiency is increased iron
demand secondary to (1) maternal and fetal blood volume
expansion during pregnancy; (2) blood volume expansion
during infancy and early childhood; or (3) chronic blood
loss, usually of GI or uterine origin.
The major consequence of iron deficiency is microcytic,
hypochromic anemia.
Ferrous sulfate, given PO, is the drug of choice for iron
deficiency.
Iron-deficient patients who cannot tolerate or absorb oral
ferrous salts are treated with parenteral iron—usually iron
dextran administered IV.
The major adverse effects of ferrous sulfate are GI disturbances. These are best managed by reducing the dosage
(rather than by administering the drug with food, which
would greatly reduce absorption).
Parenteral iron dextran carries a significant risk of fatal
anaphylactic reactions. The risk is much lower with other
parenteral iron products (e.g., iron sucrose).
When iron dextran is used, a small test dose is required
before each full dose. Be aware, however, that patients
can experience anaphylaxis and other hypersensitivity
reactions from the test dose, and patients who did not react
to the test dose may still have these reactions with the full
dose.
The principal cause of vitamin B12 deficiency is impaired
absorption secondary to lack of intrinsic factor.
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The principal consequences of B12 deficiency are megaloblastic (macrocytic) anemia and neurologic injury.
Vitamin B12 deficiency caused by malabsorption is treated
lifelong with cyanocobalamin. Traditional treatment consists
of IM injections administered monthly. However, large
oral doses administered daily are also effective, as are
intranasal doses (administered weekly with Nascobal).
For initial therapy of severe vitamin B12 deficiency, parenteral folic acid is given along with cyanocobalamin.
When folic acid is combined with vitamin B12 to treat B12
deficiency, it is essential that the dosage of B12 be adequate
because folic acid can mask continued B12 deficiency (by
improving the hematologic picture), while allowing the
neurologic consequences of B12 deficiency to progress.
The principal causes of folic acid deficiency are poor diet
(usually in patients with alcohol use disorder) and malabsorption secondary to intestinal disease.
The principal consequences of folic acid deficiency are
megaloblastic anemia and neural tube defects in the
developing fetus.
To prevent neural tube defects, all women who may become
pregnant should ingest 400 to 800 mcg of supplemental
folate daily, in addition to the folate they get in food.
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Summary of Major Nursing Implicationsa
indicative of anemia are subnormal hemoglobin levels,
subnormal hematocrit, subnormal hemosiderin in bone marrow,
and the presence of microcytic, hypochromic erythrocytes.
The cause of iron deficiency (e.g., pregnancy, occult
bleeding, menorrhagia, inadequate diet, malabsorption) must
be determined.
IRON PREPARATIONS
Carbonyl iron
Ferric ammonium citrate
Ferrous aspartate
Ferrous bisglycinate
Ferrous fumarate
Ferrous gluconate
Ferrous sulfate
Ferumoxytol
Heme-iron polypeptide
Iron dextran
Iron sucrose
Polysaccharide iron complex
Sodium–ferric gluconate complex (SFGC)
Identifying High-Risk Patients
All iron preparations are contraindicated for patients with
anemias other than iron deficiency anemia.
Parenteral preparations are contraindicated for patients
who have had a severe allergic reaction to them in the past.
Use oral preparations with caution in patients with peptic
ulcer disease, regional enteritis, and ulcerative colitis.
Except where indicated, the implications summarized here
apply to all iron preparations.
Preadministration Assessment
Therapeutic Goal
Prevention or treatment of iron deficiency anemias.
Baseline Data
Before treatment, assess the degree of anemia. Fatigue, listlessness, and pallor indicate mild anemia; dyspnea, tachycardia,
and angina suggest severe anemia. Laboratory findings
Implementation: Administration
Routes
Oral. Ferrous sulfate, ferrous fumarate, ferrous gluconate,
ferrous aspartate, ferrous bisglycinate, ferric ammonium citrate,
carbonyl iron, heme-iron polypeptide, polysaccharide iron
complex, SFGC.
Parenteral. Iron dextran, SFGC, iron sucrose, ferumoxytol.
Oral Administration
Food reduces GI distress from oral iron but also greatly reduces
absorption. Instruct patients to administer oral iron between
660
CHAPTER 55
Drugs for Deficiency Anemias
Summary of Major Nursing Implicationsa—cont’d
meals to maximize uptake. If GI distress is intolerable, the
dosage may be reduced. If absolutely necessary, oral iron
may be administered with meals.
Liquid preparations can stain the teeth. Instruct patients
to dilute liquid preparations with juice or water, administer
them through a straw, and rinse the mouth after.
Warn patients not to crush or chew sustained-release
preparations.
Warn patients against ingesting iron salts together with
antacids or tetracyclines.
Inform patients that oral iron preparations differ and warn
them against switching from one to another.
Parenteral Administration: Iron Dextran
Iron dextran may be given IV or IM. Intravenous administration is safer and preferred.
Intravenous. To minimize anaphylactic reactions, follow
this protocol: (1) Infuse 25 mg as a test dose and observe
the patient for at least 15 minutes. (2) If the test dose appears
safe, infuse 100 mg over 10 to 15 minutes. (3) If the 100-mg
dose proves uneventful, give additional doses as needed every
24 hours.
Intramuscular. Intramuscular injection can cause significant adverse reactions (anaphylaxis, persistent pain, localized
discoloration, promotion of tumors) and is generally avoided.
Make injections deep into each buttock using the Z-track
technique. Give a 25-mg test dose and wait 1 hour before
giving the full therapeutic dose.
Parenteral Administration: SFGC
To minimize adverse reactions, precede the first full dose
with a test dose (25 mg infused IV over 60 minutes).
Administer therapeutic doses by slow IV infusion (no faster
than 12.5 mg/min).
Parenteral Administration: Iron Sucrose
Hemodialysis-Dependent Patients. Administer iron
sucrose directly into the dialysis line. Do not mix with other
drugs or with parenteral nutrition solutions. Administer by
either (1) slow injection (1 mL/min) or (2) infusion (dilute
iron sucrose in up to 100 mL of 0.9% saline and infuse over
15 minutes or longer).
Peritoneal Dialysis–Dependent Patients. Administer
by slow infusion.
Non–Dialysis-Dependent Patients. Administer by slow
injection.
Parenteral Administration: Ferumoxytol
Give 510 mg by slow IV injection, defined here as 1 mL/sec
(30 mg/sec), taking about 17 seconds for the total 510-mg
dose. Repeat 3 to 8 days later.
Implementation: Measures to Enhance
Therapeutic Effects
If the diet is low in iron, advise the patient to increase
consumption of iron-rich foods (e.g., egg yolks, brewer’s yeast,
wheat germ, muscle meats, fish, fowl).
Ongoing Evaluation and Interventions
Evaluating Therapeutic Responses
Evaluate treatment by monitoring hematologic status. Reticulocyte counts should increase within 4 to 7 days, hemoglobin
content and the hematocrit should begin to rise within 1
week, and hemoglobin levels should rise by at least 2 gm/
dL within 1 month. If these responses do not occur, evaluate
the patient for adherence, persistent bleeding, inflammatory
disease, and malabsorption.
Minimizing Adverse Effects
GI Disturbances. Forewarn patients about possible GI
reactions (nausea, vomiting, constipation, diarrhea) and inform
them these will diminish over time. If GI distress is severe,
the dosage may be reduced, or if absolutely necessary, iron
may be administered with food.
Inform patients that iron will impart a harmless dark green
or black color to stools.
Anaphylactic Reactions. Parenteral iron dextran (and,
rarely, SFGC, iron sucrose, and ferumoxytol) can cause
potentially fatal anaphylaxis. Before giving parenteral iron,
ensure that injectable epinephrine and facilities for resuscitation are immediately available. After administration, observe
the patient for 60 minutes. Give test doses as described earlier.
Precede all doses of iron dextran with a test dose; test doses
are unnecessary with iron sucrose and ferumoxytol.
Managing Acute Toxicity. Iron poisoning can be fatal to
young children. Instruct parents to store iron out of reach and
in childproof containers. If poisoning occurs, rapid treatment
is imperative. Use gastric lavage to remove iron from the
stomach. Administer deferoxamine if plasma levels of iron
exceed 500 mcg/mL. Manage acidosis and shock as required.
CYANOCOBALAMIN (VITAMIN B12)
Preadministration Assessment
Therapeutic Goal
Correction of megaloblastic anemia and other sequelae of
vitamin B12 deficiency.
Baseline Data
Assess the extent of vitamin B12 deficiency. Record signs
and symptoms of anemia (e.g., pallor, dyspnea, palpitations,
fatigue). Determine the extent of neurologic damage. Assess
GI involvement.
Baseline laboratory data include plasma vitamin B12
levels, erythrocyte and reticulocyte counts, and hemoglobin
and hematocrit values. Bone marrow may be examined for
megaloblasts. A Schilling test may be ordered to assess vitamin
B12 absorption.
Identifying High-Risk Patients
Use with caution in patients receiving folic acid.
Implementation: Administration
Routes and Administration
Administration may be IM, subQ, oral, or intranasal. For most
patients, lifelong treatment is required. Traditional therapy
Continued
661
UNIT VII
Drugs That Affect the Heart, Blood Vessels, and Blood
Summary of Major Nursing Implicationsa—cont’d
consists of IM or subQ injections administered monthly.
However, treatment can be just as effective with large daily
oral doses or with intranasal doses (administered weekly
with Nascobal). Inform patients that intranasal doses should
severe megaloblastic anemia resulting from vitamin B12
deficiency; and (3) prevention of folic acid deficiency,
especially in women who might become pregnant and in
women who are pregnant or lactating.
Implementation: Measures to Enhance
Therapeutic Effects
Promoting Adherence
Patients with permanent impairment of B12 absorption require
lifelong B12 therapy. To promote adherence, educate patients
Baseline Data
Assess the extent of folate deficiency. Record signs and
symptoms of anemia (e.g., pallor, dyspnea, palpitations,
fatigue). Determine the extent of GI damage.
Baseline laboratory data include serum folate levels,
erythrocyte and reticulocyte counts, and hemoglobin and
hematocrit values. In addition, bone marrow may be evaluated
for megaloblasts. To rule out vitamin B12 deficiency, vitamin
B12 determinations and a Schilling test may be ordered.
not be administered within 1 hour before or 1 hour after
consuming hot foods or hot liquids.
about the nature of their condition, and impress upon them
the need for monthly injections, daily oral therapy, or weekly
intranasal therapy. Schedule appointments for injections at
convenient times.
Improving Nutrition
When B12 deficiency is not due to impaired absorption, a
change in diet may accelerate recovery. Advise the patient
to increase consumption of B12-rich foods (e.g., muscle meats,
dairy products).
Ongoing Evaluation and Interventions
Evaluating Therapeutic Effects
Assess for improvements in hematologic and neurologic status.
Over a period of 2 to 3 weeks, megaloblasts should disappear,
reticulocyte counts should rise, and the hematocrit should
normalize. Neurologic damage may take months to improve;
in some cases, full recovery may never occur.
For patients receiving long-term therapy, vitamin B12 levels
should be measured every 3 to 6 months, and blood counts
should be performed.
Minimizing Adverse Effects
Hypokalemia may develop during the first days of therapy.
Monitor serum potassium levels and observe the patient for
signs of potassium insufficiency. Teach patients the signs and
symptoms of hypokalemia (e.g., muscle weakness, irregular
heartbeat), and instruct them to report these immediately.
Minimizing Adverse Interactions
Folic acid can correct hematologic effects of vitamin B12
deficiency, but not the neurologic effects. By improving the
hematologic picture, folic acid can mask ongoing B12 deficiency, resulting in undertreatment and progression of neurologic injury. Accordingly, when folic acid and cyanocobalamin
are used concurrently, special care must be taken to ensure
that the cyanocobalamin dosage is adequate.
FOLIC ACID (FOLACIN, FOLATE,
PTEROYLGLUTAMIC ACID)
Identifying High-Risk Patients
Folic acid is contraindicated for patients with pernicious
anemia (except during the acute phase of treatment).
Inappropriate use of folic acid by these patients can mask
signs of vitamin B12 deficiency, allowing further neurologic
deterioration.
Implementation: Dosage and Administration
Routes
Oral, subQ, IV, and IM. Oral administration is most
common and preferred. Injections are employed only when
intestinal absorption is severely impaired.
Dosage
Prevention of Neural Tube Defects. To reduce the risk
of neural tube defects, women who might become pregnant
should consume 400 to 800 mcg of supplemental folate
daily—in addition to the folate they get from food.
Treatment of Folate-Deficient Megaloblastic Anemia.
The initial oral dosage is 1000 to 2000 mcg/day. Once
symptoms have resolved, the maintenance dosage is
400 mcg/day.
Implementation: Measures to Enhance
Therapeutic Effects
Improving Nutrition
If the diet is deficient in folic acid, advise the patient to
increase consumption of folate-rich foods (e.g., green vegetables, liver). If alcoholism underlies dietary deficiency, offer
counseling for alcoholism, as well as dietary advice.
Ongoing Evaluation and Interventions
Evaluating Therapeutic Effects
Monitor hematologic status. Within 2 weeks, megaloblasts
should disappear, reticulocyte counts should increase, and
the hematocrit should begin to rise.
Preadministration Assessment
Therapeutic Goal
Folic acid is used for (1) treatment of megaloblastic anemia
resulting from folic acid deficiency; (2) initial treatment of
Patient education information is highlighted as blue text.
a
662
CHAPTER 56
Hematopoietic Agents
KEY POINTS
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Epoetin is given to increase red blood cell counts and
thereby decrease the need for transfusions. Specific indications include anemia associated with (1) chronic renal
failure, (2) myelosuppressive cancer chemotherapy, and
(3) zidovudine therapy in patients with HIV/AIDS.
By increasing the hematocrit, epoetin can cause or exacerbate hypertension.
Epoetin increases the risk of cardiovascular events (e.g.,
cardiac arrest, stroke, HF, MI), especially when the
hemoglobin level exceeds 11 gm/dL or the rate of rise in
hemoglobin exceeds 1 gm/dL in 2 weeks.
In some cancer patients, epoetin can accelerate tumor
progression and shorten life.
Owing to the risk of serious toxicity, epoetin must be
prescribed and used under a new Risk Evaluation and
Mitigation Strategy (REMS).
Filgrastim is given to elevate neutrophil counts and thereby
reduce the risk of infection. Specific indications are chronic
severe neutropenia and neutropenia associated with cancer
chemotherapy or BMT.
The principal adverse effects of filgrastim are bone pain
and leukocytosis.
Sargramostim is used to accelerate recovery from BMT,
treat patients in whom a bone marrow transplant has failed,
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and accelerate neutrophil recovery in patients undergoing
chemotherapy for AML.
The principal adverse effect of sargramostim is
leukocytosis.
Oprelvekin is given to stimulate platelet production in
patients undergoing myelosuppressive chemotherapy for
nonmyeloid cancers. The goal is to minimize thrombocytopenia and platelet transfusions.
The principal adverse effects of oprelvekin are fluid retention (which causes edema and anemia), cardiac dysrhythmias
(tachycardia, atrial fibrillation, and atrial flutter), and severe
allergic reactions, including anaphylaxis.
TRAs are used to increase platelet production in patients
with ITP after traditional methods of treatment have failed.
Uncommon but serious effects of TRAs include bone
marrow fibrosis, hematologic malignancy, and thrombotic/
thromboembolic complications.
Since epoetin alfa, filgrastim, sargramostim, and oprelvekin
stimulate proliferation of bone marrow cells, these drugs
should be used with great caution, if at all, in patients with
cancers of bone marrow origin.
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Summary of Major Nursing Implicationsa
EPOETIN ALFA (ERYTHROPOIETIN)
Preadministration Assessment
Therapeutic Goal
Epoetin is used to restore and maintain erythrocyte counts,
and thereby decrease the need for transfusions, in patients
with CRF, HIV-infected patients receiving zidovudine, anemic
patients facing elective surgery, and cancer patients receiving
myelosuppressive chemotherapy, but only if the goal of
chemotherapy is palliation, not cure. For most patients, the
hemoglobin level should not exceed 10 or 11 mg/dL.
Implementation: Administration
Routes
IV and subQ.
Handling and Storage
Epoetin alfa is supplied in single-use and multiuse vials;
don’t re-enter the single-use vials. Don’t agitate. Don’t mix
with other drugs. Discard the unused portion of the vial.
Store at 2°C to 8°C (36°F to 46°F); don’t freeze.
Administration
Chronic Renal Failure. Administer by IV bolus or subQ
Baseline Data
All Patients. Obtain blood pressure; blood chemistry
(BUN, uric acid, creatinine, phosphorus, potassium); complete
blood counts with differential and platelet count; hemoglobin
level; degree of transferrin saturation (should be at least 20%);
and ferritin concentration (should be at least 100 ng/mL).
HIV-Infected Patients. Obtain an erythropoietin level.
If the level is above 500 milliunits/mL, epoetin is unlikely
to help.
Identifying High-Risk Patients
Avoid epoetin alfa in patients with uncontrolled hypertension,
hypersensitivity to mammalian cell–derived products or
albumin, or cancer of myeloid origin.
injection.
Chemotherapy-Induced Anemia. Administer by subQ
injection.
Zidovudine-Induced Anemia. Administer by IV or subQ
injection.
Surgery Patients. Administer by subQ injection.
Ongoing Evaluation and Interventions
Monitoring Summary
Measure hemoglobin level twice weekly until the maximum
acceptable level has been achieved (10 or 11 mg/dL for most
patients) and a maintenance dosage established. Measure
hemoglobin periodically thereafter. Obtain complete blood
counts with a differential and platelet counts routinely. Monitor
Continued
671
Summary of Major Nursing Implicationsa—cont’d
blood chemistry, including BUN, uric acid, creatinine,
phosphorus, and potassium. Monitor iron stores and maintain
at an adequate level. Monitor blood pressure.
Minimizing Adverse Effects
Hypertension. Monitor blood pressure and, if necessary,
control with antihypertensive drugs. If hypertension cannot
be controlled, reduce epoetin dosage. In patients with preexisting hypertension (a common complication of CRF), make
certain that blood pressure is controlled before epoetin use.
Cardiovascular Events. Epoetin has been associated with
an increase in cardiovascular events (e.g., cardiac arrest,
stroke, HF, and MI). Risk is greatest when the hemoglobin
level exceeds 11 gm/dL or the rate of rise in hemoglobin
exceeds 1 gm/dL in 2 weeks. To minimize risk, reduce dosage
when hemoglobin approaches 11 gm/dL or when the rate of
rise exceeds 1 gm/dL in 2 weeks, and temporarily stop dosing
if hemoglobin rises to 11 gm/dL or more. CRF patients on
dialysis may need a higher dosage of heparin to prevent
clotting in the dialysis machine.
For patients taking the drug before elective surgery,
anticoagulant treatment can reduce the risk of deep vein
thrombosis.
Cancer Patients: Tumor Progression and Shortened
Survival. Epoetin can accelerate tumor progression and
shorten survival in some cancer patients. To reduce risk,
dosage should be no higher than needed to bring hemoglobin
gradually up to 12 gm/dL. Also, epoetin should be used only
in cancer patients who are undergoing chemotherapy or
radiation therapy. Those who are not receiving chemotherapy
or radiation therapy should not take this drug.
Autoimmune Pure Red-Cell Aplasia. Epoetin use may
lead to pure red-cell aplasia (PRCA), owing to production
of neutralizing antibodies directed against epoetin and native
erythropoietin. If evidence of PRCA develops, epoetin should
be discontinued and blood assessed for neutralizing antibodies.
If PRCA is diagnosed, transfusions will be needed for life.
Patient Education. Give all patients a Medication Guide
that explains the risks and benefits of epoetin so that they
can make an informed decision on whether to use this drug.
FILGRASTIM (GRANULOCYTE
COLONY-STIMULATING FACTOR)
Preadministration Assessment
Therapeutic Goal
Filgrastim is given to promote neutrophil recovery in cancer
patients following myelosuppressive chemotherapy or BMT.
The drug is also used to treat severe chronic neutropenia.
Baseline Data
Obtain complete blood counts and platelet counts.
Identifying High-Risk Patients
Filgrastim is contraindicated for patients with hypersensitivity
to Escherichia coli–derived proteins.
Use with caution in patients with cancers of bone marrow
origin.
Implementation: Administration
Routes
IV, subQ.
Handling and Storage
Filgrastim is supplied in single-use vials. Don’t re-enter the
vial; discard the unused portion. Don’t agitate. Store at 2°C
to 8°C (36°F to 46°F); don’t freeze. Before administration,
filgrastim may be kept at room temperature for up to 24 hours.
Administration
Cancer Chemotherapy. Administer by subQ bolus, short
IV infusion, or continuous IV or subQ infusion.
Bone Marrow Transplantation. Administer by slow
IV or subQ infusion.
Chronic Severe Neutropenia. Inject subQ daily.
Ongoing Evaluation and Interventions
Evaluating Therapeutic Effects.
Obtain complete blood counts twice weekly. Discontinue
treatment when the absolute neutrophil count reaches
10,000/mm3.
Minimizing Adverse Effects
Bone Pain. Evaluate for bone pain and treat with a
nonopioid analgesic (e.g., acetaminophen). Consider an opioid
analgesic if the nonopioid is insufficient.
Leukocytosis. Massive doses can cause leukocytosis
(white blood cell counts above 100,000/mm3). If leukocytosis
develops, reduce filgrastim dosage.
SARGRAMOSTIM
(GRANULOCYTE-MACROPHAGE
COLONY-STIMULATING FACTOR)
Preadministration Assessment
Therapeutic Goal
Sargramostim is used to accelerate myeloid recovery in cancer
patients who have undergone autologous BMT following
high-dose chemotherapy (with or without concurrent irradiation). In addition, the drug is approved for treatment of patients
for whom an autologous or allogenic bone marrow transplant
has failed to take. Sargramostim is also used to accelerate
neutrophil recovery in older patients receiving induction
chemotherapy for AML.
Baseline Data
Obtain complete blood counts with differential and platelet
count.
Identifying High-Risk Patients
Sargramostim is contraindicated in the presence of hypersensitivity to yeast-derived products and excessive leukemic
myeloid blasts in bone marrow or peripheral blood.
Exercise caution in patients with cardiac disease, hypoxia,
peripheral edema, pleural or pericardial effusion, or cancers
of bone marrow origin.
Implementation: Administration
Route
IV (by infusion).
Handling and Storage
Sargramostim is supplied in concentrated solution and as
a powder, which must be reconstituted for IV infusion. To
CHAPTER 56
Hematopoietic Agents
Summary of Major Nursing Implicationsa—cont’d
reconstitute the powder, add 1 mL of sterile water and gently
swirl. Before infusing, dilute the concentrated solution or
reconstituted powder. Administer as soon as possible after
diluting—and no later than 6 hours after reconstitution. Store
sargramostim (powder, reconstituted powder, final IV solution)
at 2°C to 8°C (36°F to 46°F) until used.
Administration
Administer by 2-hour or 4-hour IV infusion.
Ongoing Evaluation and Interventions
Minimizing Adverse Effects
Leukocytosis and Thrombocytosis. Obtain complete
blood counts with differential and platelet counts twice weekly.
If the white blood cell count rises above 50,000/mm3, if the
absolute neutrophil count rises above 20,000/mm3, or if the
platelet count rises above 500,000/mm3, temporarily interrupt
sargramostim or reduce the dosage.
OPRELVEKIN (INTERLEUKIN-11)
Preadministration Assessment
Therapeutic Goal
Oprelvekin is given to minimize thrombocytopenia and the
need for platelet transfusions in patients undergoing myelosuppressive therapy for nonmyeloid cancers.
Baseline Data
Determine baseline blood cell counts and platelet count,
hematocrit, and fluid and electrolyte status.
Identifying High-Risk Patients
Use with caution in patients with cancers of myeloid origin;
in patients taking diuretics or ifosfamide; and in patients
with a history of atrial dysrhythmias, HF, pleural effusion,
or papilledema.
Implementation: Administration
Route
SubQ.
Handling and Storage
Oprelvekin is supplied in single-use vials; don’t re-enter the
vial. Don’t agitate. Don’t mix with other drugs. Discard the
unused portion of the vial. Store at 2°C to 8°C (36°F to
46°F); don’t freeze.
Administration
Administer once daily beginning 4 to 6 hours after chemotherapy. Continue for 21 days or until platelet counts exceed
50,000/mm3—whichever comes first.
Ongoing Evaluation and Interventions
Monitoring Summary
Monitor platelet counts from the time of the expected nadir
until the count exceeds 50,000/mm3. Monitor blood cell counts,
fluid status, and electrolyte status.
Minimizing Adverse Effects
Fluid Retention. Fluid retention can result in edema,
expanded plasma volume, anemia, and dyspnea. Instruct
patients with a history of congestive heart failure or pleural
effusion to contact the prescriber if dyspnea worsens.
Cardiac Dysrhythmias. Oprelvekin can cause tachycardia,
atrial flutter, and atrial fibrillation. Use caution in patients
with a history of these disorders.
ROMIPLOSTIM
Preadministration Assessment
Therapeutic Goal
Romiplostim is given to increase platelet production in patients
with ITP that has not responded to other conventional
treatments.
Baseline Data
Determine baseline blood cell counts and platelet count.
Identifying High-Risk Patients
Use with caution in patients with cancers of myeloid origin,
patients with hematologic malignancies, and patients with
hepatic or renal impairment.
Implementation: Administration
Route
SubQ.
Handling and Storage
Romiplostim is supplied in single-use vials; don’t re-enter
the vial. Don’t agitate. Protect the reconstituted medication
from light. Don’t mix with other drugs. Discard the unused
portion of the vial. Store at 2°C to 8°C (36°F to 46°F); don’t
freeze.
Administration
Administer 1 mcg/kg once weekly and adjust dose based on
platelet response. Use lowest effective dose to maintain
platelets above 50,000/mm3.
Ongoing Evaluation and Interventions
Monitoring Summary
Monitor platelet counts from the time of the expected nadir
until the count exceeds 50,000/mm3. Monitor blood cell counts
weekly until platelet counts are stable for 4 weeks. Then
monitor platelets and blood count every 2 months thereafter.
Minimizing Adverse Effects
Thrombosis/Thromboembolism. Romiplostim should
not be used to normalize platelet counts. Depending on current
platelet count, doses should be adjusted per package recommendations. In patients with chronic liver disease, portal vein
thrombosis has been reported with romiplostim use. Use
cautiously in this population of patients.
Patient education information is highlighted as blue text.
a
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CHAPTER 76
Drugs for Asthma and Chronic Obstructive Pulmonary Disease
Tobacco smoke
Air pollution
Inherited
1-antitrypsin deficiency
Inflammation of the
airway epithelium
Infiltration of inflammatory
cells and release of cytokines
(neutrophils, macrophages,
lymphocytes, leukotrienes,
interleukins)
Systemic effects
(muscle weakness, weight loss)
Inhibition of normal
endogenous antiproteases
Continuous bronchial
irritation and inflammation
Increased protease activity
with breakdown of elastin
in connective tissue of lungs
(elastases, cathepsins, etc.)
Chronic bronchitis
(bronchial edema, hypersecretion of
mucus, bacterial colonization of airways)
Emphysema
(destruction of alveolar septa and
loss of elastic recoil of bronchial walls)
Airway obstruction
Air trapping
Loss of surface area for gas exchange
Frequent exacerbations
(infections, bronchospasm)
Dyspnea
Cough
Hypoxemia
Hypercapnia
Cor pulmonale
Fig. 76.2
■
Pathogenesis of chronic bronchitis and emphysema.
Prototype Drugs
DRUGS FOR ASTHMA AND COPD
Anti-Inflammatory Drugs: Glucocorticoids
Beclomethasone (inhaled)
Prednisone (oral)
Anti-Inflammatory Drugs: Others
Cromolyn (mast cell stabilizer, inhaled)
Zafirlukast (leukotriene modifier, oral)
Bronchodilators: Methylxanthines
Theophylline
Anticholinergic Drugs
Ipratropium
Bronchodilators: Beta2-Adrenergic Agonists
Albuterol (inhaled, short acting)
Salmeterol (inhaled, long acting)
927
UNIT XIII
Respiratory Tract Drugs
TABLE 76.1
■
Overview of Major Drugs for Asthma and Chronic Obstructive Pulmonary Disease
ANTI-INFLAMMATORY DRUGS
Glucocorticoids
BRONCHODILATORS
Beta2-Adrenergic Agonists
Inhaled
Inhaled: Short Acting
Beclomethasone dipropionate [QVAR]
Budesonide [Pulmicort Flexhaler, Pulmicort Respules, Pulmicort
Turbuhaler ]
Ciclesonide [Alvesco]
Flunisolide [Aerospan]
Fluticasone propionate [Flovent HFA, Flovent Diskus]
Mometasone furoate [Asmanex Twisthaler]
Albuterol [ProAir HFA, ProAir RespiClick, Proventil HFA,
Ventolin HFA, Airomir, Apo-Salvent MDI ]
Levalbuterol [Xopenex, Xopenex HFA]
Inhaled: Long Actingc
Arformoterol [Brovana]b
Formoterol [Foradil Aerolizer, Perforomist, Oxeze Turbuhaler
Indacaterol [Arcapta Neohaler, Onbrez Breezhaler ]b
Olodaterol [Striverdi Respimat]b
Salmeterol [Serevent Diskus]c
Oral
Methylprednisolone [A-Methapred, Depo-Medrol, Medrol, Medrol
Dose-Pak]
Prednisolone [Flo-Pred, Orapred ODT, Millipred, Pediapred,
Prelone]
Prednisone [Deltasone, Winpred ]
Oral
Albuterol [VoSpire ER]
Terbutaline (generic only)
Methylxanthines
Leukotriene Modifiers
Aminophylline, oral (generic only)
Theophylline, oral [Theo-24, Elixophyllin, Theochron, Theolair
Pulmophylline , Theo ER , Uniphyl ]
Montelukast, oral [Singulair]
Zafirlukast, oral [Accolate]a
Zileuton, oral [Zyflo, Zyflo CR]a
a
Aclidinium bromide, inhaled [Tudorza Pressair]b
Glycopyrronium bromide, inhaled [Seebri Neohaler, Seebri
Breezhaler ]b
Ipratropium, inhaled [Atrovent HFA]
Tiotropium, inhaled [Spiriva, Spiriva HandiHaler, Spiriva Respimat]b
Umeclidinium, inhaled [Incruse Ellipta]
]a
IgE Antagonist
Omalizumab, subQ [Xolair]
Phosphodiesterase-4 Inhibitors
Roflumilast, oral [Daliresp, Daxas
,
Anticholinergics
Cromolyn
Cromolyn, inhaled [Nalcrom
]c
]b
BETA AGONIST/CHOLINERGIC ANTAGONIST COMBINATIONS
ANTI-INFLAMMATORY/BRONCHODILATOR COMBINATIONS
Budesonide/formoterol, inhaled [Symbicort]
Fluticasone/salmeterol, inhaled [Advair Diskus,
Advair HFA]
Fluticasone/vilanterol, inhaled [Breo Ellipta]
Mometasone/formoterol, inhaled [Dulera, Zenhale
Albuterol/ipratropium, inhaled [Combivent Respimat, Combivent
UDV ]b
Indacaterol/glycopyrronium, inhaled [Utibron Neohaler, Ultibro
Breezhaler ]b
Olodaterol/tiotropium, inhaled [Stiolto Respimat]b
Vilanterol/umeclidinium, inhaled [Anoro Ellipta]b
]
Approved only for asthma, not for chronic obstructive pulmonary disease.
Approved only for chronic obstructive pulmonary disease, not for asthma.
c
For treatment of asthma, must always be combined with an inhaled glucocorticoid.
a
b
ADMINISTERING DRUGS BY INHALATION
Most antiasthma drugs can be administered by inhalation. This
route has three advantages: (1) therapeutic effects are enhanced
by delivering drugs directly to their site of action, (2) systemic
effects are minimized, and (3) relief of acute attacks is rapid.
Four types of inhalation devices are employed: metered-dose
inhalers, Respimats, dry-powder inhalers, and nebulizers.
Metered-Dose Inhalers
Metered-dose inhalers (MDIs) are small hand-held, pressurized
devices that deliver a measured dose of drug with each actuation.
Dosing is usually accomplished with 1 or 2 inhalations. When
2 inhalations are needed, an interval of at least 1 minute should
separate the first inhalation from the second.
When using most MDIs, the patient must begin to inhale
before activating the device. This requires hand-breath coordination, making MDIs difficult to use correctly. Accordingly,
patients will need a demonstration, as well as written and
verbal instruction. Even with optimal use, only about 10% of
the dose reaches the lungs. About 80% affects the oropharynx
and is swallowed, and the remaining 10% is left in the device
or exhaled.
Spacers are devices that attach directly to the MDI to increase
delivery of drug to the lungs and decrease deposition of drug
on the oropharyngeal mucosa (Fig. 76.3). Several kinds of
spacers are available for use with MDIs. Some spacers contain
a one-way valve that activates upon inhalation, obviating the
need for good hand-breath coordination. Some spacers also
contain an alarm whistle that sounds off when inhalation is
too rapid, thus maximizing effective drug administration. They
can also prevent bronchospasm that may occur with sudden
intake of an inhaled drug.
Respimats
Respimats are inhalers that deliver drugs as a very fine mist.
Like MDIs, they are activated by the user; however, the device
does not use propellants. An advantage of this system is that
the extremely small particle size ensures greater delivery of
drug to the lungs; in addition, because less drug falls out of
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CHAPTER 76
Drugs for Asthma and Chronic Obstructive Pulmonary Disease
With Spacer
Without Spacer
Spacer
Fig. 76.3
■
57%
Inhaler device
10%
22%
Mouth and throat
81%
21%
Lungs
9%
Effect of a spacer device on the distribution of inhaled medication.
Note that, when a spacer is used, more medication reaches its site of action in the lungs,
and less is deposited in the mouth and throat.
the mist due to particle weight, there is decreased drug deposition in the mouth and oropharynx.
PATIENT-CENTERED CARE ACROSS THE
LIFE SPAN
Anti-Inflammatory Agents
Dry-Powder Inhalers
Dry-powder inhalers (DPIs) are used to deliver drugs in
the form of a dry micronized powder directly to the lungs.
Unlike MDIs, DPIs are breath activated. As a result, DPIs
don’t require the hand-breath coordination needed with MDIs,
making DPIs much easier to use. Compared with MDIs, DPIs
deliver more drug to the lungs (20% of the total released vs.
10%) and less to the oropharynx. Also, spacers are not used
with DPIs.
Life Stage
Patient Care Concerns
Children
Inhaled glucocorticoids are the preferred
long-term treatment for children of all
ages, including infants. Face masks are
recommended for the administration of
inhaled glucocorticoids to children younger
than 4 years. Alternative treatments include
cromolyn and leukotriene receptor
antagonists (e.g., montelukast), but
evidence supporting these drugs for asthma
management is lower than that supporting
inhaled glucocorticoids. Montelukast is the
only leukotriene modifier approved for
children ages 1 to 5 years.
Pregnant women
Inhaled glucocorticoids are classified in FDA
Pregnancy Risk Category Ca; however,
they are preferred for uncontrolled asthma
in pregnant women because uncontrolled
asthma is associated with greater fetal
risks. Of the leukotriene modifiers,
montelukast and zafirlukast are Pregnancy
Risk Category B,a while zileuton is Risk
Category C.a
Breast-feeding
women
Inhaled glucocorticoids are not a
contraindication to breast-feeding;
however, women taking systemic
glucocorticoids should not breast-feed.
Older adults
Benefits exceed risk. Inhaled glucocorticoids
are much safer for this population than
systemic formulations.
Nebulizers
A nebulizer is a small machine used to convert a drug solution into a mist. The droplets in the mist are much finer than
those produced by inhalers, resulting in less drug deposit on
the oropharynx and increased delivery to the lung. Inhalation
of the nebulized mist can be done through a face mask or
through a mouthpiece held between the teeth. Because the
mist produced by a nebulizer is inhaled with each breath,
hand-breath coordination is not a concern. Nebulizers take
several minutes to deliver the same amount of drug contained in
1 inhalation from an inhaler, but for some patients, a nebulizer
may be more effective than an inhaler. Although nebulizers are
usually used at home or in a clinic or hospital, these devices,
which weigh less than 10 pounds, are sufficiently portable for
use in other locations.
ANTI-INFLAMMATORY DRUGS
Anti-inflammatory drugs—especially inhaled glucocorticoids—
are the foundation of asthma and COPD therapy. These drugs
are taken daily for long-term control. Most people with asthma
require these drugs for management at some point.
As of 2020, the FDA will no longer use Pregnancy Risk Categories.
Please refer to Chapter 9 for more information.
a
929
UNIT XIII
Respiratory Tract Drugs
GLUCOCORTICOIDS
Glucocorticoids (e.g., budesonide, fluticasone) are the most
effective drugs available for long-term control of airway
inflammation. Administration is usually by inhalation, but may
also be IV or oral. Adverse reactions to inhaled glucocorticoids
are generally minor, as are reactions to systemic glucocorticoids
taken acutely. However, when systemic glucocorticoids are
used long term, severe adverse effects are likely. The basic
pharmacology of the glucocorticoids is presented in Chapter
72. Discussion here is limited to their use in asthma.
Mechanism of Antiasthma Action
Glucocorticoids reduce asthma symptoms by suppressing
inflammation. Specific anti-inflammatory effects include:
• Decreased synthesis and release of inflammatory mediators (e.g., leukotrienes, histamine, prostaglandins)
• Decreased infiltration and activity of inflammatory cells
(e.g., eosinophils, leukocytes)
• Decreased edema of the airway mucosa (secondary to
a decrease in vascular permeability)
By suppressing inflammation, glucocorticoids reduce bronchial
hyperreactivity and decrease airway mucus production. There
is also some evidence that glucocorticoids may increase the
number of bronchial beta2 receptors, as well as their responsiveness to beta2 agonists.
Use in Asthma
Glucocorticoids are used for prophylaxis of chronic asthma.
Accordingly, dosing must be done on a fixed schedule—not
PRN. Because beneficial effects develop slowly, these drugs
cannot be used to abort an ongoing attack. Glucocorticoids do
not alter the natural course of asthma, even when used in
young children.
Inhalation Use. Inhaled glucocorticoids are first-line
therapy for management of the inflammatory component of
asthma. Most patients with persistent asthma should use these
drugs daily. Inhaled glucocorticoids are very effective and are
much safer than systemic glucocorticoids.
Oral Use. Oral glucocorticoids may be required for patients
with moderate to severe persistent asthma or for management
of acute exacerbations of asthma or COPD. Because of their
potential for toxicity, these drugs are prescribed only when
symptoms cannot be controlled with safer medications (inhaled
glucocorticoids, inhaled beta2 agonists). Because the risk for
toxicity increases with duration of use, treatment should be as
brief as possible.
low. In contrast, with prolonged use of oral glucocorticoids,
adrenal suppression can be profound.
Glucocorticoids can slow growth in children and
adolescents—but these drugs do not decrease adult height.
Short-term studies have shown that inhaled glucocorticoids
slow growth; however, long-term studies indicate that adult
height, while delayed, is not reduced. Less is known regarding
whether glucocorticoids suppress growth and development of
the brain, lungs, and other organs, in part because having asthma
alone can affect organ growth. Because the benefits of inhaled
glucocorticoids tend to be much greater than the risks, current
guidelines for asthma management recommend these drugs
for children while monitoring for evidence of complications.
Long-term use of inhaled glucocorticoids may promote bone
loss. Fortunately, the amount of loss is much lower than the
amount caused by oral glucocorticoids. To minimize bone loss,
patients should (1) use the lowest dose that controls symptoms,
(2) ensure adequate intake of calcium and vitamin D, and (3)
participate in weight-bearing exercise.
There has been concern that prolonged therapy might increase
the risk for cataracts and glaucoma. While this may be an
issue of concern with continuous use of high-dose inhaled
glucocorticoids, this problem is not associated with long-term
use of low to medium doses of inhaled glucocorticoids.
Oral Glucocorticoids. When used acutely (less than 10
days), even in very high doses, oral glucocorticoids do not
cause significant adverse effects. However, prolonged therapy,
even in moderate doses, can be hazardous. Potential adverse
effects include adrenal suppression, osteoporosis, hyperglycemia, peptic ulcer disease, and, in young patients, growth
suppression.
Adrenal suppression is of particular concern. As discussed
in Chapter 72, prolonged glucocorticoid use can decrease the
ability of the adrenal cortex to produce glucocorticoids of its
own. This can be life-threatening at times of severe physiologic
stress (e.g., surgery, trauma, or systemic infection). Because
Adverse Effects
Inhaled Glucocorticoids. These preparations are largely
devoid of serious toxicity, even when used in high doses. The
most serious concern is adrenal suppression.
The most common adverse effects are oropharyngeal
candidiasis and dysphonia (hoarseness, speaking difficulty).
Both effects result from local deposition of inhaled glucocorticoids. To minimize these effects, patients should rinse the
mouth with water and gargle after each administration. Using
a spacer device can help too. If candidiasis develops, it can
be treated with an antifungal drug.
With long-term, high-dose therapy, some adrenal suppression
may develop, although the degree of suppression is generally
930
Safety Alert
COMPENSATING FOR
ADRENAL INSUFFICIENCY
When patients have been on prolonged systemic glucocorticoid
therapy, the adrenal glands decrease their endogenous production
of glucocorticoids. If systemic therapy is stopped suddenly,
as when switching from oral therapy to inhalation therapy, the
patient can die. Similarly, during times of severe physical stress
when the body would normally produce high levels of glucocorticoids, if the dose of systemic glucocorticoids is not
increased to meet the increased need, the patient can die. What
important lesson can you take from this? When discontinuing
a systemic glucocorticoid, you must be sure that it is done
gradually to allow the body to resume production of the
endogenous hormone. On the other hand, if a patient taking
systemic glucocorticoids experiences severe physical stress,
such as a motor vehicle crash, or is scheduled for a stressful
procedure such as surgery, you must make certain that the
provider remembers to prescribe additional glucocorticoids to
supplement for the endogenous hormone that the patient cannot
produce.
UNIT XIII
Respiratory Tract Drugs
Metabolism. Theophylline is metabolized in the liver. Rates of metabolism
are affected by multiple factors—age, disease, drugs—and show wide individual
variation. As a result, the plasma half-life of theophylline varies considerably
among patients. For example, although the average half-life in nonsmoking
adults is about 8 hours, the half-life can be as short as 2 hours in some adults
and as long as 15 hours in others. Smoking either tobacco or marijuana
accelerates metabolism and decreases the half-life. The average half-life in
children is 4 hours. Metabolism is slowed in patients with certain pathologies
(e.g., heart disease, liver disease, prolonged fever). Some drugs (e.g., cimetidine,
fluoroquinolone antibiotics) decrease theophylline metabolism. Other drugs
(e.g., phenobarbital) accelerate metabolism. Because of these variations in
metabolism, dosage must be individualized.
Drug Levels. Safe and effective therapy requires periodic measurement
of theophylline blood levels. Traditionally, dosage has been adjusted to produce
theophylline levels between 10 and 20 mcg/mL. However, many patients
respond well at 5 mcg/mL, and, as a rule, there is little benefit to increasing
levels above 15 mcg/mL. Therefore, levels between 5 and 15 mcg/mL are
appropriate for most patients. At levels above 20 mcg/mL, the risk for significant
adverse effects is high.
the following dose should not be doubled, because doing so could produce
toxicity. Smokers require higher-than-average doses. Conversely, patients with
heart disease, liver dysfunction, or prolonged fever are likely to require lower
doses. Patients should be instructed not to chew the sustained-release tablets or
capsules. Product information should be consulted for compatibility with food.
The initial dosage is based on the age and weight of the patient and on
the presence or absence of factors that can impair theophylline elimination.
Specific initial dosages are described in the prescribing information in the
package insert. As noted previously, maintenance doses should be adjusted
to produce drug levels in the therapeutic range—typically 5 to 15 mcg/mL.
Intravenous. Intravenous theophylline is reserved for emergencies.
Administration must be done slowly, because rapid injection can cause fatal
cardiovascular reactions. Intravenous theophylline is incompatible with many
other drugs. Accordingly, compatibility should be verified before mixing
theophylline with other IV agents. For specific IV dosages, refer to the discussion
of aminophylline that follows.
Toxicity
Aminophylline is a theophylline salt that is considerably more soluble than
theophylline itself. In solution, each molecule of aminophylline dissociates
to yield two molecules of theophylline. Hence, the pharmacologic properties
of aminophylline and theophylline are identical. Aminophylline is available
in formulations for oral and IV dosing. Intravenous administration is employed
most often.
Administration and Dosage
Intravenous. Because of its relatively high solubility, aminophylline is
the preferred form of theophylline for IV use. Infusions should be done slowly
(no faster than 25 mg/min), because rapid injection can produce severe
hypotension and death. The usual loading dose of theophylline is 4.6 mg/kg
(5.7 mg/kg as aminophylline). The maintenance infusion rate should be adjusted
to provide plasma levels of theophylline that are within the therapeutic range
(10 to 20 mcg/mL). Aminophylline solutions are incompatible with many
other drugs. Therefore, compatibility must be verified before mixing aminophylline with other IV agents.
Oral. Aminophylline is available in 100- and 200-mg tablets. Dosing
guidelines are the same as for theophylline.
Symptoms. Toxicity is related to theophylline levels. Adverse effects
are uncommon at plasma levels below 20 mcg/mL. At 20 to 25 mcg/mL,
relatively mild reactions occur (e.g., nausea, vomiting, diarrhea, insomnia,
restlessness). Serious adverse effects are most likely at levels above 30 mcg/
mL. These reactions include severe dysrhythmias (e.g., ventricular fibrillation)
and convulsions that can be highly resistant to treatment. Death may result
from cardiorespiratory collapse.
Treatment. At the first indication of toxicity, dosing with theophylline
should stop. Absorption can be decreased by administering activated charcoal
together with a cathartic. Ventricular dysrhythmias respond to lidocaine.
Intravenous diazepam may help control seizures.
Drug Interactions
Caffeine. Caffeine is a methylxanthine with pharmacologic properties
like those of theophylline (see Chapter 36). Accordingly, caffeine can intensify
the adverse effects of theophylline on the CNS and heart. In addition, caffeine
can compete with theophylline for drug-metabolizing enzymes, causing
theophylline levels to rise. Because of these interactions, individuals taking
theophylline should avoid caffeine-containing beverages (e.g., coffee, many
soft drinks) and other sources of caffeine.
Tobacco and Marijuana Smoke. Smoking tobacco or marijuana can
induce theophylline metabolism, resulting in increased drug clearance of up
to 50% in adults and 80% in older adults. (Secondhand smoke can result in
similarly decreased drug levels.) Consequently, if a smoking patient stops
smoking but the dose of theophylline is not decreased, the patient is at risk
for theophylline toxicity over time.
Drugs That Reduce Theophylline Levels. Several agents—including
phenobarbital, phenytoin, and rifampin—can lower theophylline levels by
inducing hepatic drug-metabolizing enzymes. Concurrent use of these agents
may necessitate an increase in theophylline dosage.
Drugs That Increase Theophylline Levels. Several drugs—including
cimetidine and the fluoroquinolone antibiotics (e.g., ciprofloxacin)—can elevate
plasma levels of theophylline, primarily by inhibiting hepatic metabolism. To
avoid theophylline toxicity, the dosage of theophylline should be reduced
when the drug is combined with these agents.
Formulations
Theophylline is available for IV and oral use. For IV use, generic solutions
are available in concentrations of 400 mg/250 mL, 400 mg/500 mL, or
800 mg/500 mL of solution.
For oral use, the following concentrations are available.
•
•
•
•
•
•
Elixophyllin oral elixir: 80 mg/15 mL
Generic oral solution: 80 mg/15 mL
Theochron 12-hour extended-release tablets: 100, 200, and 300 mg
Generic 12-hour extended-release tablets: 100, 200, 300, and 450 mg
Theo-24 24-hour extended-release capsules: 100, 200, 300, and 400 mg
Generic 24-hour extended-release tablets: 400 and 600 mg
Unlike the elixir and oral solution, the sustained-release tablets and capsules
produce drug levels that are relatively stable. Accordingly, the sustained-release
formulations are preferred for routine therapy.
Dosage and Administration
Oral. Dosage must be individualized. To minimize chances of toxicity,
doses should be low initially and then gradually increased. If a dose is missed,
Other Methylxanthines
Aminophylline
ANTICHOLINERGIC DRUGS
Anticholinergic drugs improve lung function by blocking muscarinic receptors
in the bronchi, reducing bronchoconstriction. Two agents are available:
ipratropium and tiotropium. These drugs are approved only for COPD but
are used off-label for asthma. Both drugs are administered by inhalation. The
principal difference between the two is pharmacokinetic: Tiotropium has a
much longer duration of action and thus can be dosed less often. With both
drugs, systemic effects are minimal.
Ipratropium
Actions and Therapeutic Use
Ipratropium [Atrovent HFA] is an atropine derivative administered by inhalation
to relieve bronchospasm. The drug has FDA approval only for bronchospasm
associated with COPD, but is often used off-label for asthma and is included
in current evidence-based guidelines from the National Asthma Education
and Prevention Program (NAEPP) for asthma management. Like atropine,
ipratropium is a muscarinic antagonist. By blocking muscarinic cholinergic
receptors in the bronchi, ipratropium prevents bronchoconstriction. Therapeutic
effects begin within 30 seconds, reach 50% of their maximum in 3 minutes,
and persist about 6 hours. Ipratropium is effective against allergen-induced
asthma and EIB, but is less effective than the beta2 agonists. However, because
ipratropium and the beta2-adrenergic agonists promote bronchodilation by
different mechanisms, their beneficial effects are additive.
Adverse Effects
Systemic effects are minimal because ipratropium is a quaternary ammonium
compound and therefore always carries a positive charge. As a result, the
drug is not readily absorbed from the lungs or from the digestive tract. The
most common adverse reactions are dry mouth and irritation of the pharynx.
If systemic absorption is sufficient, the drug may raise intraocular pressure
in patients with glaucoma. Adverse cardiovascular events (heart attack, stroke,
death) have occurred in people taking ipratropium; however, because absorption
is minimal, it seems unlikely that ipratropium is the cause.
938