Antihypertensive Agents
Hypertension
High blood pressure
• Normal: Systolic < 130 mm
Hg Diastolic < 85 mm Hg
Classification of Blood Pressure
Category
Hg)
Systemic BP (mm Hg)
Diastolic BP (mm
Normal
<130
<85
High normal
130-139
85-89
Hypertension
Stage 1
Stage 2
Stage 3
Stage 4
140-159
160-169
180-209
 210
90-99
100-109
110-119
 120
Classification of Blood Pressure
Primary Hypertension
• Specific cause unknown
• 90% of the cases
• Also known as essential or idiopathic
hypertension
Secondary Hypertension
• Cause is known (such as eclampsia of
•
pregnancy, renal artery disease,
pheochromocytoma)
10% of the cases
Blood Pressure = CO x SVR
• CO = Cardiac output
• SVR = Systemic vascular resistance
Blood Pressure =
Cardiac Output
X
Peripheral Resistance
Preload
Contractility
Heart Rate
Vasoconstriction
Venous Arteriolar Venous
Circulating
Fluid Volume
Renal
Sodium
Handling
Sympathetic
Nervous
System
Renin
Angiotensin
Aldosterone
System
Vascular remodeling
Vascular
Smooth
Muscle
Afterload
a2
Volume
Kidneys
Vasomotor center
Cardiac Output
Heart
b1
Renin
b1
Ang I
Preload
Ang II
Aldosterone
b2
BP= CO x TPVR
Capacitance venules
Resistance arterioles
TPVR
Total Peripheral Vascular Resistance (TPVR)
a1
VSMCs
Vascular
Smooth
Muscle
Cells
Antihypertensive Agents
• Medications used to treat hypertension
Antihypertensive Agents
 Therapeutic goals in hypertension
To lower the high blood pressure and
reduced cardiovascular morbidity and
mortality by least intrusive means.
 For most of the HTN patients: life-long
treatment of an asymptomatic disease
Antyhepertensive Drugs
New End-Points
 Effects on hard end-points
 Mortality
 Stroke
 Heart attacks
 Effects on end-organ damage
 Left ventricular and vascular
hypertophy
 Effects on renal function
 Effects on metabolic status
 Blood lipids and glucose
Antihypertensive Agents:
Categories
• Adrenergic agents
• Angiotensin-converting enzyme inhibitors
• Angiotensin II receptor blockers
• Calcium channel blockers
• Diuretics
• Vasodilators
Antihypertensive Agents:
Categories
• Adrenergic Agents
– Alpha1 blockers
– Beta blockers (cardioselective and
nonselective)
– Centrally acting alpha blockers
– Combined alpha-beta blockers
– Peripheral-acting adrenergic agents
Beta Blockers ( … lol)
Afterload
a2
Volume
Kidneys
Vasomotor center
Cardiac Output
Heart
b1
Renin
b1
Ang I
Preload
Ang II
Aldosterone
b2
BP= CO x TPVR
a1
VSMCs
Capacitance venules
Resistance arterioles
TPVR
b - Blockers
Beta Blockers
_____________________________
Mechanisms and Sites of Action
_
- Reduction in cardiac output
- Inhibition of renin release
Negative Chronotropic- CNS effects
in venous return
& Inotropic Effects - Reduction
and plasma volume
- Reduction in peripheral resistance
- Improvement in vascular
compliance
- Resetting of baroreceptor levels
- Effects on prejunctional b2 receptors
Inhibition of
- Attenuation of pressor response to
catecholamines (stress, exercise)
Renin Release
_____________________________
_
Beta Blockers
 Cardioselectivity (Beta-1 vs Beta-2 )
 Intrinsic Sympathomimetic Activity (ISA;
partial agonistic activity)
 Affinity for alpha-1 adrenergic receptors
(Labetalol, Carvedilol)
Beta Blockers
 There are 15 Beta blockers on the market in

the US
Approved for hypertension (13) and for one or
more of following indications:
 Angina pectoris
 Myocardial Infarction
 Ventricular arrhythmia
 Migraine prophylaxis
 Heart Failure
 Perioperative Hypertension
Beta Blockers ( …lol)
 Beta-1,2-Non-Selective
 Propranolol [INDERAL]
 Nadolol [CORGARD]
 Carteolol [CARTROL] *
 Timolol [BLOCADREN]
 Pindolol [VISKEN] *
X  Sotalol [BETAPACE]
 Penbutol [LEVATOL] *
 Beta-1-Selective
 Acebutolol [SECTRAL] *
 Atenolol [TENORMIN]
 Betaxolol [KERIONE]
 Bisoprolol [ZEBETA]
X  Esmolol [BREVIBLOC]
 Metoprolol
[LOPRESSOR ]
 Beta-1,2/Alpha 1Selective
 Labetalol [TRANDATE, NORMODYNE]
 Carvedilol [COREG]
* - ISA
Beta Blockers
 Side Effects:








Bronchospasm
Bradicardia/heart block
Mask and prolong the symptoms of hypoglycemia
Abrupt withdrawal can precipitate MI
Cold extremities, Raynaud’s phenomenon,
intermittent claudication
Decreased exercise tolerance; fatigue, depression
and impotence
CNS: sleep disturbance, vivid dreams, nightmares
Effects of plasma lipids
Beta Blockers
 YES: (useful
in)
 Younger
patients
 Anxious
patients
 Angina
pectoris
 Post-MI
patient
 No: (avoid in)
 Patients with COPD
 IDDM
 Pateints with
peripheral
vascular disease
 Raynaud’s syndrome
 2nd and 3rd degree
block
 Energetic patients
Antihypertensive Agents:
Mechanism of Action
Adrenergic Agents
Alpha1 Blockers (peripherally acting)
• Block the alpha1-adrenergic receptors
• The SNS is not stimulated
Result: DECREASED blood pressure
• Stimulation of alpha1-adrenergic receptors
causes HYPERtension
• Blocking alpha1-adrenergic receptors causes
decreased blood pressure
Afterload
a2
Volume
Kidneys
Vasomotor center
Cardiac Output
Heart
b1
Renin
b1
Ang I
Preload
Ang II
Aldosterone
BP= CO x TPVR
a1
a1
a1
Capacitance venules
Resistance arterioles
TPVR
a1 Receptors
Blockers
a1
a1- Receptor Blockers
Inhibition of Vasoconstriction
Induced by Endogenous
Catecholamines at
Arterioles and Veins
Reduced Peripheral Resistance
and
Reduced Preload
Antihypertensive Agents:
Adrenergic Agents
Alpha1 Blockers
• doxazosin (Cardura)
• prazosin (Minipress)
• terazosin (Hytrin)
Antihypertensive Agents:
Mechanism of Action
Adrenergic Agents
Central-Acting Adrenergics
• Stimulate alpha2-adrenergic receptors
• Sympathetic outflow from the CNS is decreased
Result: decreased blood pressure
Antihypertensive Agents:
Adrenergic Agents
Central-Acting Adrenergics
• clonidine (Catapres)
• methyldopa (Aldomet)
(drug of choice for hypertension in pregnancy)
Afterload
a2
Volume
Kidneys
Vasomotor center
Cardiac Output
Heart
b1
Renin
b1
Ang I
Preload
Ang II
Aldosterone
BP= CO x TPVR
VSMC
Capacitance venules
Resistance arterioles
TPVR
Central
a2 Agonists
Central a2–Agonists
Diminished CNS
Sympathetic Outflow
Activation of Pre-synaptic
Alpha-2 Receptors Reduces
NE & EPI Release at Synapse
Alpha-2 Agonist
Post-synaptic
Effector
Rostral
Ventrolateral
Medulla
Pre-synaptic Neuron
Alpha-2 Receptor
NE & EPI
Alpha-1 Receptor
Beta Receptor
Antihypertensive Agents:
Mechanism of Action
Adrenergic Agents
Adrenergic Neuronal Blockers
(peripherally acting)
• Inhibit release of norepinephrine
• Also deplete norepinephrine stores
• SNS (peripheral adrenergic nerves) is not stimulated
Result: decreased blood pressure
Antihypertensive Agents:
Adrenergic Agents
Adrenergic Neuronal Blockers
(peripherally acting)
• reserpine
• guanadrel (Hylorel)
• guanethidine (Ismelin)
Antihypertensive Agents:
Adrenergic Agents
Therapeutic Uses
• Alpha1 blockers (peripherally acting)
– Treatment of hypertension
– Relief of symptoms of BPH
– Management of of severe CHF when used
with cardiac glycosides and diuretics
Antihypertensive Agents:
Adrenergic Agents
Therapeutic Uses
• Central-Acting Adrenergics
– Treatment of hypertension, either alone or
with other agents
– Usually used after other agents have failed
due to side effects
– Also may be used for treatment of severe
dysmenorrhea, menopausal flushing, glaucoma
– Clonidine is useful in the management of
withdrawal symptoms in opioid- or nicotinedependent persons
Antihypertensive Agents:
Adrenergic Agents
Therapeutic Uses
• Adrenergic neuronal blockers
(peripherally acting)
– Treatment of hypertension, either alone or
with other agents
– Seldom used because of frequent side effects
Antihypertensive Agents:
Adrenergic Agents
Side Effects
Most common: dry mouth
drowsiness
sedation
constipation
Other:
headaches sleep disturbances
nausea
rash
cardiac
disturbances (palpitations)
HIGH INCIDENCE OF ORTHOSTATIC HYPOTENSION
Antihypertensive Agents:
Categories
Angiotensin-Converting Enzyme Inhibitors
(ACE Inhibitors)
• Large group of safe and effective drugs
• Often used as first-line agents for CHF
•
and hypertension
May be combined with a thiazide diuretic
or calcium channel blocker
An giotensin
Peripheral resistance
Renal
function
II
Cardiovascular structure
1. Non-hemodynamic
1. Direct vasoconstriction
1. Increases Na+ reabsorption effects:
2. Enhancement of
peripheral noradrenergic
neurotransmission
2. Releases aldosterone from
3. Increased central (CNS)
sympathetic discharge
4. Release of catecholamines
from adrenal medulla
Rapid
Pressor Response
adrenal cortex
- Increased expression
of
proto-oncogenes
- Increased production
3. Altered renal hemodynamics:
of
- renal vasoconstriction
growth factors
- increased noradrenergic
- Increased synthesis of
neurotransmission in
extracellular matrix
kidney
proteins
- Increased renal sympathetic
tone (CNS)
2. Hemodynamic effects:
- Increased afterload
(cardiac)
- Increased wall
Cardiovascular
Slow
tension
Hypertrophy and
(vascular)
Pressor Response
Remodeling
Afterload
a2
Volume
Kidneys
Vasomotor center
Cardiac Output
Heart
b1
Renin
b1
Ang I
Preload
Ang II
Aldosterone
b2
BP= CO x TPVR
a1
VSMCs
Capacitance venules
Resistance arterioles
TPVR
ACE Inhibitors
mRNA
mRNA
ACE
mRNA
Angiotensinogen Reni
n
Ang II
Ang I
Angiotensinogen
Angiotensinogen
Local (tissue) RAS:
Intrinsic; Extrinsic
(myocyte
)
(VSM
cells)
Renin
ACE
Renin (renal)
tissue
A
T1
A endothelial
T1 cell
(autocrine)
Ang I
Ang II
Angiotensinogen
Ang I
Ang II
(liver)
blood vessel
(paracrine)
(endocrine)
ACE
mRNA
Reni
n
mRNA
Angiotensinogen
mRNA
ACE
Angiotensin Converting
Enzyme
Angiotensinogen
Kininogens
Kallikrein
Renin
Angiotensin I
Bradykinin
ACEIs
ACEIs
ACE
Angiotensin II
Inactive
Peptides
BK receptors
AT-1 receptors
ACEIs : Prevention of renal disease
INTRAGLOMERULAR PRESSURE
Arterial
pressure
+
Angiotensin II
++
+
Afferent
arteriole
Angiotensin II
20
mmHg
Bowman’s
capsule
Efferent
arteriole
excess glomerular
pressure
hyperfiltration
microalbuminuria
Antihypertensive Agents:
Mechanism of Action
ACE Inhibitors
RAAS: Renin Angiotensin-Aldosterone System
• When the enzyme angiotensin I is converted to
angiotensin II, the result is potent vasoconstriction
and stimulation of aldosterone
• Result of vasoconstriction: increased systemic
vascular resistance and increased afterload
• Therefore, increased BP
Antihypertensive Agents:
Mechanism of Action
ACE Inhibitors
• Aldosterone stimulates water and sodium
•
resorption.
Result: increased blood volume, increased
preload, and increased B
Antihypertensive Agents:
Mechanism of Action
ACE Inhibitors
• ACE Inhibitors block the angiotensin-converting
•
enzyme, thus preventing the formation of
angiotensin II.
Also prevent the breakdown of the vasodilating
substance, bradykinin
Result: decreased systemic vascular resistance
(afterload), vasodilation, and therefore, decreased
blood pressure
Antihypertensive Agents
ACE Inhibitors
• captopril (Capoten)
• Short half-life, must be dosed more frequently
than others
• enalapril (Vasotec)
• The only ACE inhibitor available in oral and
parenteral forms
• lisinopril (Prinivil and Zestril) and quinapril (Accupril)
• Newer agents, long half-lives, once-a-day dosing
• Several other agents available
Antihypertensive Agents:
Therapeutic Uses
ACE Inhibitors
• Hypertension
• CHF (either alone or in combination with
•
•
diuretics
or other agents)
Slows progression of left ventricular hypertrophy
after an MI
Renal protective effects in patients with diabetes
Drugs of choice in hypertensive patients with CHF
Antihypertensive Agents:
Side Effects
ACE Inhibitors
• Fatigue
• Headache
• Impaired taste
Dizziness
Mood changes
Dry, nonproductive cough, reverses when therapy is stopped
NOTE: first-dose hypotensive effect may occur!!
Antihypertensive Agents:
Categories
Angiotensin II Receptor Blockers
(A II Blockers or ARBs)
• Newer class
• Well-tolerated
• Do not cause coughing
ACE Inhibitors vs AT1 Antagonists
Example: Fibrinolytic System
Angiotensinogen
Kininogens
Kallikrein
Bradykinin
Renin
ACE
Is
ACE
Angiotensin I
Inactive Peptides
+
Plasminogen
Activators
Endothelial Cell
Angiotensin II
PAI-1
PAI-1
+
Afterload
a2
Volume
Kidneys
Vasomotor center
Cardiac Output
Heart
b1
Renin
b1
Ang I
Preload
Ang II
Ang II
Aldosterone
b2
BP= CO x TPVR
a1
VSMCs
Capacitance venules
Resistance arterioles
TPVR
Ang II
Ang II Receptor
Blockers
Antihypertensive Agents:
Mechanism of Action
Angiotensin II Receptor Blockers
• Allow angiotensin I to be converted to
•
angiotensin II, but block the receptors that
receive angiotensin II
Block vasoconstriction and release of
aldosterone
Antihypertensive Agents:
Angiotensin II Receptor Blockers
• losartan (Cozaar)
• eposartan (Teveten)
• valsartan (Diovan)
• irbesartan (Avapro)
• candesartan (Atacand)
• telmisartan (Micardis)
Antihypertensive Agents:
Therapeutic Uses
Angiotensin II Receptor Blockers
• Hypertension
• Adjunctive agents for the treatment of CHF
• May be used alone or with other agents such
as diuretics
Antihypertensive Agents:
Side Effects
Angiotensin II Receptor Blockers
• Upper respiratory infections
• Headache
• May cause occasional dizziness, inability to
sleep, diarrhea, dyspnea, heartburn, nasal
congestion, back pain, fatigue
Antihypertensive Agents:
Categories
Calcium Channel Blockers
• Benzothiazepines
• Dihydropyridines
• Phenylalkylamines
Afterload
a2
Volume
Kidneys
Vasomotor center
Cardiac Output
Heart
b1
Renin
b1
Ang I
AV
Preload
Ang II
Aldosterone
BP= CO x TPVR
Ca++
Capacitance venules
Resistance arterioles
TPVR
L-type Ca++
channels
Calcium Channel
Blockers
Antihypertensive Agents:
Mechanism of Action
Calcium Channel Blockers
• Cause smooth muscle relaxation by blocking the
•
•
binding of calcium to its receptors, preventing
muscle contraction
This causes decreased peripheral smooth muscle
tone, decreased systemic vascular resistance
Result: decreased blood pressure
Calcium Channel Blockers
Mechanisms and Sites of
Action
Block transmembrane entry of calcium into arteriolar smooth
muscle cells and cardiac myocytes thus inhibiting excitationcontraction
Negative Inotropic and
Chronotropic Effects
Produce Vasorelaxation
at Arterioles
L-type Ca++ channels
Reduced Peripheral Resistance
Nifed>Dilti+Verap
Verap+Dilti>Nifed
Antihypertensive Agents
Calcium Channel Blockers
• Benzothiazepines:
– diltiazem (Cardizem, Dilacor)
• Phenylalkamines:
– verapamil (Calan, Isoptin)
• Dihydropyridines:
– amlodipine (Norvasc), bepridil (Vascor),
nicardipine (Cardene)
Antihypertensive Agents:
Therapeutic Uses
Calcium Channel Blockers
• Angina
• Hypertension
• Dysrhythmias
• Migraine headaches
Antihypertensive Agents:
Side Effects
Calcium Channel Blockers
• Cardiovascular
– hypotension, palpitations, tachycardia
• Gastrointestinal
– constipation, nausea
• Other
– rash, flushing, peripheral edema, dermatitis
Antihypertensive Agents:
Diuretics
• Decrease the plasma and extracellular fluid
volumes
• Results:
resistance
decreased preload
decreased cardiac output
decreased total peripheral
• Overall effect: decreased workload of the
heart,
and decreased blood pressure
Antihypertensive Agents:
Mechanism of Action
Vasodilators
• Directly relaxes arteriolar smooth muscle
• Result:
response,
decreased systemic vascular
decreased afterload, and
PERIPHERAL
VASODILATION
Antihypertensive Agents
Vasodilators
• diazoxide (Hyperstat)
• hydralazine HCl (Apresoline)
• minoxidil (Loniten, Rogaine)
• sodium nitroprusside (Nipride, Nitropress)
Afterload
a2
Volume
Kidneys
Vasomotor center
Cardiac Output
Heart
b1
Renin
b1
Ang I
Preload
b2
Ang II
Aldosterone
BP= CO x TPVR
NO → cGMP → Ca++
Capacitance venules
Resistance arterioles
TPVR
a1
Peripheral
Vasodilators
Antihypertensive Agents:
Therapeutic Uses
Vasodilators
• Treatment of hypertension
• May be used in combination with other agents
• Sodium nitroprusside and diazoxide IV are
reserved for the management of hypertensive
emergencies
Antihypertensive Agents: Side Effects
Vasodilators
• Hydralazine:
– dizziness, headache, anxiety, tachycardia,
nausea and vomiting, diarrhea, anemia,
dyspnea, edema, nasal congestion
• Sodium nitroprusside:
– bradycardia, hypotension, possible
cyanide toxicity
Antihypertensive Agents:
Nursing Implications
• Before beginning therapy, obtain a
thorough health history and head-to-toe
physical examination.
• Assess for contraindications to specific
antihypertensive agents.
• Assess for conditions that require cautious
use of these agents.
Antihypertensive Agents:
Nursing Implications
• Educate patients about the importance of not
missing a dose and taking the medications
exactly as prescribed.
• Patients should never double up on doses if a
dose is missed; check with physician for
instructions on what to do if a dose is missed.
• Monitor BP during therapy. Instruct patients to
keep a journal of regular BP checks.
Antihypertensive Agents:
Nursing Implications
• Instruct patients that these drugs should not be
stopped abruptly, as this may cause a rebound
hypertensive crisis, and perhaps lead to CVA.
• Oral forms should be given with meals so that
absorption is more gradual and effective.
• Administer IV forms with extreme caution and
use an IV pump.
Antihypertensive Agents:
Nursing Implications
• Remind patients that medications is only part of
therapy. Encourage patients to watch their diet,
stress level, weight, and alcohol intake.
• Patients should avoid smoking and eating foods
high in sodium.
• Encourage supervised exercise.
Antihypertensive Agents:
Nursing Implications
• Instruct patients to change positions slowly to
avoid syncope from postural hypotension.
• Patients should report unusual shortness of
breath; difficulty breathing; swelling of the feet,
ankles, face, or around the eyes; weight gain or
loss; chest pain; palpitations; or excessive
fatigue.
Antihypertensive Agents:
Nursing Implications
• Men taking these agents may not be aware that
impotence is an expected effect. This may
influence compliance with drug therapy.
• If patients are experiencing serious side effects,
or believe that the dose or medication needs to
be changed, they should contact their physician
immediately.
Antihypertensive Agents:
Nursing Implications
• Hot tubs, showers, or baths; hot weather;
prolonged sitting or standing; physical exercise;
and alcohol ingestion may aggravate low blood
pressure, leading to fainting and injury. Patients
should
sit or lie down until symptoms subside.
• Patients should not take any other medications,
including OTC drugs, without first getting the
approval of their physician.
Antihypertensive Agents:
Nursing Implications
• Monitor for side/adverse effects
(dizziness, orthostatic hypotension, fatigue)
and for toxic effects.
• Monitor for therapeutic effects
• Blood pressure should be maintained at less
than 140/90 mm Hg
Diuretic Agents
Diuretic Agents
• Drugs that accelerate the rate of urine
formation.
• Result: removal of sodium and water
Afterload
a2
Volume
Kidneys
Vasomotor center
Cardiac Output
Heart
b1
Renin
b1
Ang I
Preload
Ang II
Aldosterone
b2
BP= CO x TPVR
a1
VSMCs
Capacitance venules
Resistance arterioles
TPVR
DIURETICS
Sodium
• Where sodium goes, water follows.
• 20 to 25% of all sodium is reabsorbed
into the bloodstream in the loop of Henle,
5 to 10% in the distal tubules, and 3%
in collecting ducts.
• If it is not absorbed, it is excreted with
the urine.
Diuretics
Inhibition of
Sodium Reabsorption
Reduced Circulating Volume
Reduced Preload
Reduced Cardiac Output
Diuretic Agents
• Carbonic anhydrase inhibitors
• Loop diuretics
• Osmotic diuretics
• Potassium-sparing diuretics
• Thiazide and thiazide-like diuretics
Carbonic Anhydrase Inhibitors
(CAIs)
• acetazolamide (Diamox)
• methazolamide
• dichlorphenamide
Carbonic Anhydrase Inhibitors:
Mechanism of Action
• The enzyme carbonic anhydrase helps to make
H+ ions available for exchange with sodium and
water in the proximal tubules.
• CAIs block the action of carbonic anhydrase,
thus preventing the exchange of H+ ions with
sodium
and water.
Carbonic Anhydrase Inhibitors:
Mechanism of Action
• Inhibition of carbonic anhydrase reduces H+ ion
concentration in renal tubules.
• As a result, there is increased excretion of
bicarbonate, sodium, water, and potassium.
• Resorption of water is decreased and urine
volume is increased.
Carbonic Anhydrase Inhibitors:
Therapeutic Uses
• Adjunct agents in the long-term management
of open-angle glaucoma
• Used with miotics to lower intraocular pressure
before ocular surgery in certain cases
• Also useful in the treatment of:
– Glaucoma
– Edema
– Epilepsy
– High-altitude sickness
Carbonic Anhydrase Inhibitors:
Therapeutic Uses
• Acetazolamide is used in the management of
edema secondary to CHF when other diuretics
are not effective.
• CAIs are less potent diuretics than loop diuretics
or thiazides—the metabolic acidosis they induce
reduces their diuretic effect in 2 to 4 days.
Carbonic Anhydrase Inhibitors:
Side Effects
Metabolic acidosis
Anorexia
Hematuria
Photosensitivity
Drowsiness
Paresthesias
Urticaria
Melena
Loop Diuretics
• bumetanide (Bumex)
• ethacrynic acid (Edecrin)
• furosemide (Lasix)
Loop Diuretics:
Mechanism of Action
• Act directly on the ascending limb of the
loop of Henle to inhibit sodium and chloride
resorption.
• Increase renal prostaglandins, resulting in the
dilation of blood vessels and reduced
peripheral vascular resistance.
Loop Diuretics: Drug Effects
• Potent diuresis and subsequent loss of fluid
• Decreased fluid volume causes:
– Reduced BP
– Reduced pulmonary vascular resistance
– Reduced systemic vascular resistance
– Reduced central venous pressure
– Reduced left ventricular end-diastolic pressure
• Potassium depletion
Loop Diuretics:
Therapeutic Uses
• Edema associated with CHF or hepatic
or renal disease
• Control of hypertension
Loop Diuretics: Side Effects
Body System
CNS
vision
GI
Effect
Dizziness, headache,
tinnitus, blurred
Nausea, vomiting,
diarrhea
Loop Diuretics: Side Effects
Body System
Hematologic
Metabolic
Effect
Agranulocytosis,
neutropenia,
thrombocytopenia
Hypokalemia,
hyperglycemia,
hyperuricemia
Osmotic Diuretics
• mannitol (Resectisol, Osmitrol)
Osmotic Diuretics:
Mechanism of Action
• Work in the proximal tubule
• Nonabsorbable, producing an osmotic
effect
• Pull water into the blood vessels and
nephrons from the surrounding tissues
Osmotic Diuretics: Drug Effects
• Reduced cellular edema
• Increased urine production, causing
diuresis
• Rapid excretion of water, sodium, and
other electrolytes, as well as excretion of
toxic substances from the kidney
• Reduces excessive intraocular pressure
Osmotic Diuretics:
Therapeutic Uses
• Used in the treatment of patients in the
early, oliguric phase of ARF
• To promote the excretion of toxic
substances
• Reduction of intracranial pressure
• Treatment of cerebral edema
Osmotic Diuretics: Side Effects
• Convulsions
• Thrombophlebitis
• Pulmonary congestion
Also headaches, chest pains, tachycardia,
blurred vision, chills, and fever
Potassium-Sparing Diuretics
• amiloride (Midamor)
• spironolactone (Aldactone)
• triamterene (Dyrenium)
Afterload
a2
Volume
Kidneys
Vasomotor center
Cardiac Output
Heart
b1
Renin
b1
Ang I
Preload
Ang II
Aldosterone
b2
BP= CO x TPVR
a1
VSMCs
Capacitance venules
Resistance arterioles
TPVR
Aldosterone
Antagonists
Potassium-Sparing Diuretics:
Mechanism of Action
• Work in collecting ducts and distal
convoluted tubules
• Interfere with sodium-potassium exchange
• Competitively bind to aldosterone
receptors
• Block the resorption of sodium and water
usually induced by aldosterone
Potassium-Sparing Diuretics:
Drug Effects
• Prevent potassium from being pumped
into the tubule, thus preventing its
secretion
• Competitively block the aldosterone
receptors and inhibit its action
• The excretion of sodium and water
is promoted
Potassium-Sparing Diuretics:
Therapeutic Uses
spironolactone and triamterene
• Hyperaldosteronism
• Hypertension
• Reversing the potassium loss caused by
• potassium-losing drugs
amiloride
• Treatment of CHF
Potassium-Sparing Diuretics:
Side Effects
Body System
Effect
CNS
Dizziness, headache
GI
Other
Cramps, nausea,
vomiting, diarrhea
Urinary frequency,
weakness
**hyperkalemia
Potassium-Sparing Diuretics:
Side Effects
spironolactone
• gynecomastia, amenorrhea, irregular menses
Thiazide and Thiazide-Like
Diuretics
• hydrochlorothiazide (Esidrix, HydroDIURIL)
• chlorothiazide (Diuril)
• trichlormethiazide (Metahydrin)
• Thiazide-like
• chlorthalidone (Hygroton)
• metolazone (Mykrox, Zaroxolyn)
Thiazide and Thiazide-Like Diuretics:
Mechanism of Action
• Inhibit tubular resorption of sodium and
chloride ions
• Action primarily in the ascending loop of
Henle and early distal tubule
• Result: water, sodium, and chloride are
excreted
• Potassium is also excreted to a lesser extent
• Dilate the arterioles by direct relaxation
Thiazide and Thiazide-Like
Diuretics: Drug Effects
• Lowered peripheral vascular resistance
• Depletion of sodium and water
Thiazide and Thiazide-Like
Diuretics: Therapeutic Uses
• Hypertension
(one of the most prescribed group of agents for
this)
• Edematous states
• Idiopathic hypercalciuria
• Diabetes insipidus
• Adjunct agents in treatment of CHF, hepatic
cirrhosis
Thiazide and Thiazide-Like
Diuretics: Side Effects
Body System
Effect
CNS
Dizziness, headache,
blurred vision, paresthesias,
decreased libido
Anorexia, nausea, vomiting,
diarrhea
GI
Thiazide and Thiazide-Like
Diuretics: Side Effects
Body System
Effect
GU
Integumentary
Metabolic
Impotence
Urticaria, photosensitivity
Hypokalemia, glycosuria,
hyperglycemia
Diuretic Agents:
Nursing Implications
• Perform a thorough patient history and physical
examination.
• Assess baseline fluid volume status, intake and
output, serum electrolyte values, weight, and
vital signs.
• Assess for disorders that may contraindicate the
use of, or necessitate cautious use of, these
agents.
Diuretic Agents:
Nursing Implications
• Instruct patients to take in the morning as much
as possible to avoid interference with sleep
patterns.
• Monitor serum potassium levels during therapy.
• Potassium supplements are usually not
recommended when potassium levels exceed
3.0 mEq/L.
Diuretic Agents:
Nursing Implications
• Teach patients to maintain proper nutritional
and fluid volume status.
• Teach patients to eat more potassium-rich foods
when taking any but the potassium-sparing
agents.
• Foods high in potassium include bananas,
oranges, dates, raisins, plums, fresh vegetables,
potatoes, meat, and fish.
Diuretic Agents:
Nursing Implications
• Patients taking diuretics along with a digitalis
preparation should be taught to monitor for
digitalis toxicity.
• Diabetic patients who are taking thiazide and/or
loop diuretics should be told to monitor blood
glucose and watch for elevated levels.
Diuretic Agents:
Nursing Implications
• Teach patients to change positions slowly, and
to rise slowly after sitting or lying to prevent
dizziness and possible fainting related to
orthostatic hypotension.
• Encourage patients to keep a log of their
daily weight.
• Encourage patients to return for follow-up visits
and lab work.
Diuretic Agents: Nursing
Implications
• Patients who have been ill with nausea,
vomiting, and/or diarrhea should notify their
physician as fluid loss may be dangerous.
• Signs and symptoms of hypokalemia include
muscle weakness, constipation, irregular pulse
rate, and overall feeling of lethargy.
Diuretic Agents:
Nursing Implications
• Instruct patients to notify the physician
immediately if they experience rapid heart rates
or syncope (reflects hypotension or fluid loss).
• A weight gain of 2 or more pounds a day
or 5 or more pounds a week should be
reported immediately.
Diuretic Agents:
Nursing Implications
Monitor for adverse effects:
• metabolic alkalosis, drowsiness, lethargy,
hypokalemia, tachycardia, hypotension, leg
cramps, restlessness, decreased mental
alertness
Diuretic Agents:
Nursing Implications
• Monitor for therapeutic effects:
– Reduction in edema, fluid volume overload,
CHF
– Reduction of hypertension
– Return to normal intraocular pressures
Antilipemic Agents
Antilipemics
• Drugs used to lower lipid levels
Triglycerides and Cholesterol
• Two primary forms of lipids in the blood
• Water-insoluble fats that must be bound
to apoproteins, specialized lipid-carrying
proteins
• Lipoprotein is the the combination of
triglyceride or cholesterol with apoprotein
Types of Lipoproteins
Lipid
Content Lipoprotein Classification
Most chylomicron


Least
very-low density lipoprotein
(VLDL)
Protein
Content
Least

Intermediate-density lipoprotein
(IDL)

High-density lipoprotein (HDL) Most
Instructors may want to insert
EIC Image #84:
Cholesterol Homeostasis
Coronary Heart Disease
• The risk of CHD in patients with
cholesterol levels of 300 mg/dL is 3 to 4
times greater than that in patients with
levels less than
300 mg/dL
Antilipemics
• Bile acid sequestrants
• HMG-CoA reductase inhibitors
(HMGs or statins)
• Fibric acid derivatives
• Niacin (nicotinic acid)
Antilipemics: Bile Acid
Sequestrants
• cholestyramine (Questran)
• colestipol hydrochloride (Colestid)
• Also called bile acid-binding resins and
ion-exchange resins
Antilipemics: Bile Acid
Sequestrants
Mechanism of Action
• Prevent resorption of bile acids from small
•
intestine
Bile acids are necessary for absorption
of cholesterol
Antilipemics: Bile Acid
Sequestrants
Therapeutic Uses
• Type II hyperlipoproteinemia
• Relief of pruritus associated with partial biliary
obstruction (cholestyramine)
Antilipemics: Bile Acid
Sequestrants
Side Effects
• Constipation
– Heartburn, nausea, belching, bloating
These adverse effects tend to disappear over
time
Antilipemics: HMG-CoA
Reductase Inhibitors (HMGs or
statins)
• lovastatin (Mevacor)
• pravastatin (Pravachol)
• simvastatin (Zocor)
• atorvastatin (Lipitor)
• cerivastatin (Baycol)
• fluvastatin (Lescol)
Most potent LDL reducers
Antilipemics:
HMG-CoA Reductase Inhibitors
Mechanism of Action
• Inhibit HMG-CoA reductase, which is used by the
•
liver to produce cholesterol
Lower the rate of cholesterol production
Antilipemics:
HMG-CoA Reductase Inhibitors
Therapeutic Uses
• Treatment of type IIa and IIb hyperlipidemias
– Reduce LDL levels by 30 to 40%
– Increase HDL levels by 2 to 15%
– Reduce triglycerides by 10 to 30%
Antilipemics:
HMG-CoA Reductase Inhibitors
Side Effects
• Mild, transient GI disturbances
• Rash
• Headache
• Myopathy (muscle pain)
• Elevations in liver enzymes
Antilipemics: Fibric Acid
Derivatives
• clofibrate
• gemfibrozil (Lopid)
• fenofibrate (Tricor)
Antilipemics: Fibric Acid
Derivatives
Mechanism of Action
• Believed to work by activating lipase,
which breaks down cholesterol
• Also suppress release of free fatty acid
from the adipose tissue, inhibit synthesis
of triglycerides in the liver, and increase
the secretion of cholesterol in the bile
Antilipemics: Fibric Acid
Derivatives
Therapeutic Uses
• Treatment of type IV and V hyperlipemias
• Treatment of type III, IV, and V
hyperlipidemias
Decrease the triglyceride levels and increase
HDL by as much as 25%
Antilipemics: Fibric Acid
Derivatives
Side Effects
• Abdominal discomfort
• Diarrhea
• Nausea
• Blurred vision
• Increased risk of gallstones
• Prolonged prothrombin time
• Liver studies may show increased function
Antilipemics: Niacin (Nicotinic
Acid)
• Vitamin B3
• Lipid-lowering properties require much
higher doses than when used as a vitamin
• Effective, inexpensive, often used in
combination with other lipid-lowering
agents
Antilipemics: Niacin (Nicotinic
Acid)
Mechanism of Action
• Thought to increase activity of lipase, which
•
breaks down lipids
Reduces the metabolism or catabolism of
cholesterol and triglycerides
Antilipemics: Niacin (Nicotinic
Acid)
Therapeutic Uses
• Effective in lowering triglyceride, total serum
•
•
cholesterol, and LDL levels
Increases HDL levels
Effective in the treatment of types IIa, IIb, III,
IV,
and V hyperlipidemias
Antilipemics: Niacin (Nicotinic
Acid)
Side Effects
• Flushing (due to histamine release)
• Pruritus
• GI distress
Antilipemics: Nursing
Implications
• Before beginning therapy, obtain a
thorough health and medication history.
• Assess dietary patterns, exercise level,
weight, height, VS, tobacco and alcohol
use, family history.
• Assess for contraindications, conditions
that require cautious use, and drug
interactions.
Antilipemics: Nursing
Implications
• Contraindications include biliary
obstruction, liver dysfunction, active liver
disease.
• Obtain baseline liver function studies.
• Patients on long-term therapy may need
supplemental fat-soluble vitamins (A, D,
K).
• Take with meals to decrease GI upset.
Antilipemics: Nursing
Implications
• Patient must be counseled concerning diet and
•
•
•
nutrition on an ongoing basis.
Instruct on proper procedure for taking the
medications.
Powder forms must be taken with a liquid,
mixed thoroughly but not stirred, and NEVER
taken dry.
Other medications should be taken 1 hour
before
or 4 to 6 hours after meals to avoid interference
with absorption.
Antilipemics: Nursing
Implications
• Clofibrate often causes constipation;
instruct patients to increase fiber and fluid
intake to offset this effect.
• To minimize side effects of niacin, start on
low initial dose and gradually increase it,
and take with meals.
• Small doses of aspirin or NSAIDs may be
taken 30 minutes before niacin to
minimize cutaneous flushing.
Antilipemics: Nursing
Implications
• Inform patients that these agents may
take several weeks to show effectiveness.
• Instruct patients to report persistent GI
upset, constipation, abnormal or unusual
bleeding, and yellow discoloration of the
skin.
Antilipemics: Nursing
Implications
• Monitor for side effects, including
increased liver enzyme studies.
• Monitor for therapeutic effects:
– Reduced cholesterol and triglyceride levels