HYPERTENSION
Navdeep Singh
Marivic Zerrudo
INTRODUCTION
The heart is a hollow muscular
organ that is somewhat pyramid
and lies within the pericardium
in the mediastinum.
Reference: Snell
SURFACES
OF THE HEART
•Sternocostal surface
•Diaphragmatic surface
•Base of the heart
•Apex of the heart
BORDERS
•Apex – left ventricle, 5th left intercostal space 3.5 in
from the midline
•Superior – formed by the roots of the great blood
vessels, extends from a point on the 2nd left costal
cartilage 0.5 in from the edge of the sternum to a
point on the 3rd right costal cartilage from the edge of
the sternum
•Right border – right atrium, extends from a point on
the 3rd right costal cartilage 0.5 in from the edge of
the sternum downward to a point on the 6th right
costal cartilage 0.5 in from the edge of the sternum
BORDERS
•Left border – left ventricle, extends from a
point on the 2nd left costal cartilage 0.5 in
from the edge of the sternum to the apex
beat of the heart
•Inferior border – right ventricle and the
apical part of the left ventricle, extends from
a point on the 6th right costal cartilage 0.5 in
from the edge of the sternum to the apex
beat
ANATOMY OF THE HEART
HEART ANATOMY
Chambers
Right atrium
Right
ventricle
Left atrium
Left ventricle
VALVES
 Semilunar
valves
 Aortic valve
 Pulmonary valve
 Atrioventricular
valves
 Mitral valve
 Tricuspid valve
SPECIALIZED EXCITATORY
AND CONDUCTING MYOCYTES
o Sinoatrial (SA) node
pacemaker of the
heart
o Atrioventricular (AV)
node
o Bundle of His
o Right and left bundle
branches
BLOOD SUPPLY:
(3) Major Epicardial Coronary arteries:
a. Left Anterior Descending Artery
- Anterior wall
- Anterior two thirds of septum
- Entire apex of heart, circumferentially
b. Left Circumflex Coronary Artery
- Posterior, lateral left aspect of heart.
c. Right Coronary Artery
- Posterior one third of septum, inferior aspect,
and posterior wall of heart
BLOOD VESSELS: TYPES
Arteries and arterioles – carry blood away from
the heart
Arterioles – control conduits
- Has a strong muscular wall that can close
the arteriole completely or can, by relaxing,
dilate it several fold, thus, can regulate
blood flow and pressure
Capillaries – where nutrient and gas exchange
occur
Veins and venules – carry blood toward the
heart.
- much less smooth muscle
HYPERTENSION
Definitions:
 A progressive cardiovascular syndrome arising
from complex and interrelated etiologies
 Early markers of the syndrome often are present
before elevated blood pressure is observed.
Therefore, hypertension cannot be classified
solely by discrete blood pressure thresholds.
 Progression is strongly associated with functional
and structural cardiac and vascular
abnormalities that damage the heart, kidney,
brain vasculature, and other organs and lead to
premature morbidity and death.
Pharmacy Times (Hypertension: Beyond JNC 7) page 32, March 2006
EPIDEMIOLOGY
prevalence of hypertension
 blood pressure levels
 rate of age-related
blood pressure increase

vary among countries
and among
subpopulations within
a country.

Hypertension is present in all populations

It accounts for 6 % of deaths worldwide.

Reference: Harrison
EPIDEMIOLOGY
Top ten provinces with the highest hypertension
prevalence
Guimaras (80.1%)
2. Camiguin (60.4%)
3. Quirino (54.1%)
4. Sultan Kudarat (51.4%)
5. Pasay City (50.7%)
6. Muntinlupa City (50.6%)
7. Las Pinas (49.1%)
8. Davao Oriental (44.8%)
9. Catanduanes (40.9%)
10. Kalinga (39.3%).
1.
Reference: http://www.nscb.gov.ph/ncs/10thNCS/papers/contributed%20papers/cps-10/cps10-02.pdf
EPIDEMIOLOGY
Bottom ten province/area with the lowest
hypertension prevalence
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
San Juan (0%)
Marinduque (2.6%)
Tawi Tawi (3.0%)
Navotas (4.6%)
Northern Samar (5.2%)
Misamis Occidental (8.3%)
Masbate (8.5%)
Bataan (10.4%)
Siquijor (10.43%)
Sorsogon(11.4%)
Reference: http://www.nscb.gov.ph/ncs/10thNCS/papers/contributed%20papers/cps-10/cps10-02.pdf
MORTALITY STATISTICS > HYPERTENSIVE HEART
DISEASE (2004) BY COUNTRY
RANK
COUNTRIES
DEATHS
# 1 United States:
23,761 deaths
# 2 Germany:
13,253 deaths
# 3 Brazil:
11,561 deaths
# 4 Romania:
9,347 deaths
# 5 Mexico:
3,795 deaths
# 6 Colombia:
3,672 deaths
# 7 Japan:
3,375 deaths
# 8 South Africa:
3,216 deaths
# 9 Poland:
2,741 deaths
# 10 Hungary:
2,713 deaths
Reference: http://www.nationmaster.com/graph/mor_hyp_hea_dis-mortality-hypertensive-heart-desease
EPIDEMIOLOGY
Prevalence of Hypertension in the U.S. (HARRISON’S INTERNAL MEDICINE)
33.5 % among Hispanic Blacks
28.9 % among Hispanic Whites
20.7 % among Mexican Americans
Out of the world, incidence of high blood pressure is
highest in African Americans
 36.7% of African American men have high blood
pressure
 One in three blacks have hypertension
 30% of African American male deaths are connected to
hypertension/high blood pressure
 27.9% of Latin American male deaths are connected to
hypertension/high blood pressure

EPIDEMIOLOGY



In the United States, average systolic blood pressure is
higher for men than for women during early
adulthood.
At age 60 and older, systolic blood pressures of women
are higher than men.
Diastolic blood pressure increases progressively with
age until about 55 years old, after which, it tends to
decrease.
EPIDEMIOLOGY
 Philippines
9.6M are hypertensive
15.4M are predisposed to be hypertensive
among adults, 20 years and over
 for over 5 years, hypertension ranks as the
fifth leading cause of morbidity


Reference: http://www.nscb.gov.ph/ncs/10thNCS/papers/contributed%20papers/cps-10/cps10-02.pdf 2005
EPIDEMIOLOGY
Hypertension increases with age.
 Among aged ≥ 60, prevalence is 65.4 %.
 In African Americans, it appears earlier.

Obesity and weight gain are strong and independent
risk factors.
 Sixty percent of hypertensive patients are > 20 %
overweight.

TYPES OF HYPERTENSION
 PRIMARY
HYPERTENSION
 90 % of all cases, high BP with na apparent
cause
 Factors – genetics, race, gender, age, diet,
weight, lifestyle
 SECONDARY HYPERTENSION

10 % of all cases, high BP by pre-existing physical
condition such as kidney or thyroid condition
MECHANISMS OF HYPERTENSION
 intravascular
volume
 autonomic nervous system
 renin-angiotensin-aldosterone
system
 vascular mechanisms.
INTRAVASCULAR
VOLUME
Primary determinant of arterial pressure over the long
term
Cardiac output
• Directly related to stroke volume and heart rate
• Directly related to arterial pressure
• There is an increase with arterial pressure with
increased cardiac output. This occurs with increased
blood volume.
CO = SV x HR
Arterial pressure = CO x TPR
AUTONOMIC NERVOUS SYSTEM

Maintains cardiovascular homeostasis via pressure,
volume, and chemoreceptor signals.
Adrenergic reflexes modulate blood pressure over the
short term.
 Adrenergic function with hormonal and volume related
factors contributes to the long term regulation of blood
pressure.

RENIN- ANGIOTENSIN-ALDOSTERONE
SYSTEM

It contributes to blood pressure regulation via
 the vasoconstrictor properties of angiotensin II
 the sodium retaining properties of aldosterone.
Renin is an aspartyl protease found in the kidney.
Active renin once relased into the circulation cleaves
angiotensinogen to form an inactive decopeptide,
angiotensin I.
A converting enzyme, located primarily but not
exclusively in the pulmonary circulation, converts
angiotensin I to the active octapeptide, angiotensin II.
Angiotensin II further stimulates release of aldosterone.
RENIN- ANGIOTENSIN-ALDOSTERONE
SYSTEM
 Primary
Stimuli for Renin Secretion
Decreased NaCl transport in the thick
ascending loop of Henle
Decreased pressure or stretch within the
renal afferent arteriole
Sympathetic nervous system stimulation of
renin-secreting cells via ß1 adrenoreceptors
RENIN- ANGIOTENSIN-ALDOSTERONE
SYSTEM
VASCULAR MECHANISMS


The decrease in lumen size of blood vessels
significantly increases resistance.
 This contributes to increased peripheral resistance.
 This may occur in cases of arteriosclerosis where
there is plaque formation in the vessel wall reducing
the diameter of a lumen.
The stiffness of a blood vessel also contributes to
resistance.
 It is found in most hypertensive patients and in the
elderly.
IDENTIFIABLE CAUSES OF HYPERTENSION


Chronic kidney disease
 Renal parenchymal disease
 Altered excretory function – defects in renal
excretion of salt and water
 Altered RAAS – ischemic changes resulting from
intrarenal scarring may activate the RAAS abd
contribute to hypertension in patient with early or
advanced renal failure
Coarctation of the aorta
IDENTIFIABLE CAUSES OF HYPERTENSION

Cushing’s syndrome
glucocorticoid excess resulting from exogenous
glucocorticoid therapy
 Hypertension may occur because cortisol has
mineralocorticoid-like effects and therefore leads to the
retention of sodium and water



Other glucocorticoid excess states – remediable
hyperaldosteronism
Chronic steroid therapy
IDENTIFIABLE CAUSES OF HYPERTENSION

Drug induced or drug related

Oral contraceptives – hypertension occurs as a result of estrogeninduced increases in angiotensin synthesis in the liver
Obstructive uropathy
 Primary aldosteronism and other mineralocorticoid
excess states

By inducing sodium and water retention leading to
expansion of the ECF volume
 Often accompanied by hypokalemia because
mineralocorticoids promote renal potassium excretion in the
collecting duct of the nephron


Pheochromocytoma

Tumors of the adrenal medulla increases the secretion of the
catecholamines leading to hypertension
IDENTIFIABLE CAUSES OF HYPERTENSION

Renovascular hypertension

Result from complex interplay between activation of the
renin-angiotensin-angiotensin-aldosterone system and the
sympathetic nervous sytem

Sleep apnea

Thyroid or parathyroid disease
GENETICS OF HYPERTENSION

Genetic abnormalities associated with several rare
forms of hypertension, includes the following:





mineralocorticoid-remediable aldosteronism
11beta-hydroxylase and 17alpha-hydroxylase deficiencies
Liddle’s syndrome, the syndrome of apparent
mineralocorticoid excess
pseudohypoaldosteronism type
Candidate genes
angiotensinogen
 alpha-adducin, beta- and DA-adrenergic receptors
 beta-3 subunit of G proteins

RISK FACTORS:
Modifiable
 Unhealthy lifestyle
which include
 Cigarette smoking
 unmanaged stress
 salty food
consumption
 physical inactivity
 being overweight
Reference:
http://www.nscb.gov.ph/ncs/10thNCS/papers/contributed%20
papers/cps-10/cps10-02.pdf
Non modifiable factors
 genetic predisposition
to hypertension
 disease condition like
 diabetes
 heart disease
 kidney disease
 high cholesterol
level
 stroke
 increasing age
PATIENT EVALUATION:
Objectives:
 to assess lifestyle and identify other
cardiovascular risk factors or concomitant
disorders that may affect prognosis and guide
treatment
 to reveal identifiable causes of high BP
 to assess the presence or absence of target organ
damage and CVD
PATIENT EVALUATION:
 Patient




evaluation methods
medical history
physical examination
routine laboratory tests
 Urinalysis, CBC, electrolytes, renal
function test, FBS, total cholesterol,
HDL, 12-L ECG
Optional laboratory tests
 Creatinine clearance, microalbuminuria,
24-hr urinary protein, blood calcium, uric
acid, fasting triglycerides/LDL, HgbA1C,
TSH, Echocardiography
PATIENT EVALUATION:

The physical examination includes the following:
 an appropriate measurement of BP
 with verification in the contralateral arm; an
examination of the optic fundi
 a calculation of body mass index (BMI) (measurement
of waist circumference is also very useful)
 an auscultation for carotid, abdominal, and femoral
bruits; a palpation of the thyroid gland
 a thorough examination of the heart and lungs
 an examination of the abdomen for enlarged kidneys,
masses, distended urinary bladder, and abnormal
aortic pulsation
 a palpation of the lower extremities for edema and
pulses
 Neurological assessment.
DIAGNOSIS:
Because most individuals with hypertension do not
exhibit any symptoms or feelings of malaise, they may
assume that their blood pressure is normal.
 Occasionally, if blood pressure reaches extreme levels,
individuals may experience some symptoms, such as
the following:
 Dizziness
 Diplopia
 Headache
 Shortness of breath
 Chest pain
 Abdominal pain

JNC-7 BLOOD PRESSURE CLASSIFICATION
Classification
Systolic Pressure Diastolic Pressure
< 120
< 80
120-139
80-89
Stage 1
140-159
90-99
Stage 2
>159
>100
Pre-hypertension
Hypertension
ACCURATE BLOOD PRESSURE
MEASUREMENT IN THE OFFICE
Persons should be seated quietly for atleast 5 minutes
in a chair, with feet on the floor, and arm supported at
heart level.
 Caffeine, exercise, and smoking should be avoided for
at least 30 minutes prior to measurement.
 Measurement of BP in the standing position is
indicated periodically, especially in those at risk for
postural hypotension, prior to necessary drug dose or
adding a drug, and in those who report symptoms
consistent with reduced BP upon standing.
 An appropriately sized cuff (cuff bladder encircling at
least 80 percent of the arm) should be used to ensure
accuracy.

ACCURATE BLOOD PRESSURE
MEASUREMENT IN THE OFFICE
At least two measurements should be made and the
average recorded.
 For manual determinations, palpated radial pulse
obliteration pressure should be used to estimate SBP—
the cuff should then be inflated 20–30 mmHg above
this level for the auscultatory determinations; the cuff
deflation rate for auscultatory readings should be 2
mmHg per second.
 SBP is the point at which the first of two or more
Korotkoff sounds is heard (onset of phase 1), and the
disappearance of Korotkoff sound (onset of phase 5) is
used to define DBP.
 Clinicians should provide to patients, verbally and in
writing, their specific BP numbers and the BP goal of
their treatment.

TREATMENT
Although there is no known cure
to hypertension, it is treatable
using various pharmacologic and
nonpharmacologic measures.
GOALS OF THERAPY




The ultimate public health goal of antihypertensive
therapy is to reduce cardiovascular and renal morbidity
and mortality.
Since most persons with hypertension, especially those
>50 years of age, will reach the DBP goal once the SBP
goal is achieved, the primary focus should be on
attaining the SBP goal.
Treating SBP and DBP to targets that are <140/90
mmHg is associated with a decrease in CVD
complications.
In patients with hypertension and diabetes or renal
TREATMENT

Non-pharmacologic


Lifestyle modification
Pharmacologic






Thiaz
BB
ACEI
ARB
ALDO ANT
CCB
ACHIEVING BLOOD PRESSURE CONTROL IN
INDIVIDUAL PATIENTS:
Therapy begins with lifestyle modification
 The maximum protection against combined
cardiovascular endpoints is achieved with pressures
<135–140 mmHg for systolic blood pressure and <80–
85 mmHg for diastolic blood pressure
 More aggressive blood pressure targets for blood
pressure control (e.g., blood pressure < 130/80 mmHg)
may be appropriate for patients with diabetes, CHD,
chronic kidney disease, or with additional
cardiovascular disease risk factors.
 In diabetic patients, effective blood pressure control
reduces the risk of cardiovascular events and death as
well as the risk for microvascular disease
(nephropathy, retinopathy).

ACHIEVING BLOOD PRESSURE CONTROL IN
INDIVIDUAL PATIENTS:




Risk reduction is greater in diabetic than in nondiabetic
individuals.
If BP goal is not achieved via lifestyle modification,
thiazide-type diuretics should be used as initial therapy for
most patients, either alone or in combination with one of
the other classes (ACEIs, ARBs, BBs, CCBs) that have also
been shown to reduce one or more hypertensive
complications in randomized controlled outcome trials.
If the initial drug selected is not tolerated or is
contraindicated, then a drug from one of the other classes
proven to reduce cardiovascular events should be
substituted.
Since most hypertensive patients will require two or more
antihypertensive medications to achieve their BP goals,
addition of a second drug from a different class should be
initiated when use of a single agent in adequate doses fails
to achieve the goal.
ACHIEVING BLOOD PRESSURE CONTROL IN
INDIVIDUAL PATIENTS:
When BP is >20 mmHg above systolic goal or 10 mmHg
above diastolic goal, consideration should be given to
initiate therapy with two drugs, either as separate
prescriptions or in fixed-dose combinations.
 The initiation of therapy with more than one drug
increases the likelihood of achieving BP goal in a more
timely fashion.
 The use of multidrug combinations often produce
greater BP reduction at lower doses of the component
agents, resulting in fewer side effects.
 The use of fixed-dose combinations may be more
convenient and simplify the treatment regimen, and
may cost less than the individual components
prescribed separately.

ACHIEVING BLOOD PRESSURE CONTROL IN
INDIVIDUAL PATIENTS:
Use of generic drugs should be considered to reduce
prescription costs, and the cost of separate
prescription of multiple drugs available generically
may be less than nongeneric, fixed-dose combinations.
 The starting dose of most fixed-dose combinations is
usually below the doses used in clinical outcome trials,
and the doses of these agents should be titrated
upward to achieve the BP goal before adding other
drugs.
 Caution is advised in initiating therapy with multiple
agents, particularly in some older persons and in
those at risk for orthostatic hypotension, such as
diabetics with autonomic dysfunction.

LIFESTYLE MODIFICATIONS



Adoption of healthy lifestyles by all persons is critical for
the prevention of high BP and is an indispensable part
of the management of those with hypertension.
Weight loss of as little as 10 lbs (4.5 kg) reduces BP
and/or prevents hypertension in a large proportion of
overweight persons, although the ideal is to maintain
normal body weight.
BP is also benefited by adoption of the Dietary
Approaches to Stop Hypertension (DASH) eating plan
which is a diet rich in fruits, vegetables, and lowfat
dairy products with a reduced content of dietary
cholesterol as well as saturated and total fat
LIFESTYLE MODIFICATIONS



Reduce dietary sodium intake to no 2–8 mmHg94-96
more than 100 mmol per day (2.4 g sodium or 6 g
sodium chloride).
Engage in regular aerobic physical 4–9 mmHg activity
such as brisk walking (at least 30 min per day, most
days of the week).
Moderation of alcohol - limit consumption to no more
than 2–4 mmHg consumption
PHARMACOLOGIC TREATMENT
A large number of drugs are currently available
for reducing BP.
 More than two-thirds of hypertensive individuals
cannot be controlled on one drug and will require
two or more antihypertensive agents selected
from different drug classes.
 In hypertensive patients with lower BP goals or
with substantially elevated BP, three or more
antihypertensive drugs may be required.

DIURETICS
Low-dose thiazide diuretics are often used as first-line
agents, alone or in combination with other
antihypertensive drugs.
 Thiazides inhibit the Na+/Cl– pump in the distal
convoluted tubule and, hence, increase sodium
excretion. Long term, they may also act as vasodilators.
 Thiazides are safe, efficacious, and inexpensive and
reduce clinical events.
 They provide additive blood pressure–lowering effects
when combined with beta blockers, ACE inhibitors, or
angiotensin receptor blockers.

DIURETICS
In contrast, addition of a diuretic to a calcium channel
blocker is less effective.
 Usual doses of hydrochlorothiazide range from 6.25–50
mg/d. Owing to an increased incidence of metabolic side
effects (hypokalemia, insulin resistance, increased
cholesterol), higher doses are generally not
recommended.
 The main pharmacologic target for loop diuretics is the
Na+-K+-2Cl– cotransporter in the thick ascending limb
of the loop of Henle.
 Loop diuretics are generally reserved for hypertensive
patients with reduced glomerular filtration rates
[reflected in serum creatinine > 220 mol/L (>2.5
mg/dL)], CHF, or sodium retention and edema for some
other reason such as treatment with a potent
vasodilator, e.g., minoxidil.

DIURETICS
Indapamide – non-thiazide sulfonamide diuretic with
both diuretic and vasodilator activity
 Amiloride – inhibits smooth muscle responses to
contractile stimuli, probably through effects on
transmembrane and intracellular calcium movement
that are independent of its action on sodium excretion
 Thiazide diuretics – appropriate for most patients
with mild to moderate HTN and normal renal and
cardiac fxn
 Loop diuretics – powerful for severe HTN
 Potassium-sparing diuretics – Useful both to avoid
excessive potassium depletion, particularly in patients
taking digitalis and to enhance the natriuretic effects of
other diuretics

DIURETICS

Loop diuretics
 1As
Drug
Total daily oral dose
Bumetanide
0.5 – 2 mg
Ethacrynic acid
50 – 200 mg
Furosemide
20 – 80 mg
Torsemide
5 – 20 mg
single dose or in two divided doses
POTASSIUM-SPARING DIURETICS & COMBINATION PREPARATIONS
TRADE NAME
AGENT
HYDROCHLOROTHIAZI
DE
Adactazide
Spironolactone 25 mg
Aldactone
Spironolactone 25, 50, 100
mg
Dyazide
Triamterene 37.5 mg
Dyrenium
Triamterene 50 or 100 mg
Inspra 1
Eplerenone 25, 50 or 100 mg
Maxzide
Triamterene 75 mg
50 mg
Maxzide-25 mg
Triamterene 37.5 mg
25 mg
Midamor
Amiloride 5 mg
Moduretic
Amiloride 5 mg
 1Eplerenone
50 mg
25 mg
50 mg
is currently approved for use only in HTN
DIURETICS
DRUG
TOTAL
DAILY
ORAL
DOSE
FREQUENCY OF
ADMINISTRATION
Bendroflumethiazid 2.5-10 mg
e
Single dose
Chlorothiazide
0.5-2 g
Two divided doses
Chlorthalidone1
25-50 mg
Single dose
Hydrochlorothiazide 25-100 mg
Single dose
Hydroflumethiazide 12.5-50 mg
Two divided doses
Indapamide1
2.5-10 mg
Single dose
Methyclothiazide
2.5-10 mg
Single dose
Metolazone1
2.5-10 mg
Single dose
Polythiazide
1-4 mg
Single dose
Quinethazone1
25-100 mg
Single dose
Trichlormethiazide
1-4 mg
Single dose
1Not
a thiazide but a sulfonamide qualitatively similar to the thiazides
BLOCKERS OF THE RENIN-ANGIOTENSIN
SYSTEM
ACE inhibitors decrease the production of angiotensin
II, increase bradykinin levels, and reduce sympathetic
nervous system activity. Angiotensin II receptor
blockers provide selective blockade of AT1 receptors,
and the effect of angiotensin II on unblocked AT2
receptors may augment the hypotensive effect.
 Both classes of agents are effective antihypertensive
agents that may be used as monotherapy or in
combination with diuretics, calcium antagonists, and
alpha-blocking agents.
 Side effects of ACE inhibitors and angiotensin receptor
blockers include functional renal insufficiency due to
efferent renal arteriolar dilatation in a kidney with a
stenotic lesion of the renal artery.

BLOCKERS OF THE RENIN-ANGIOTENSIN
SYSTEM
Additional predisposing conditions to renal
insufficiency induced by these agents include
dehydration, CHF, and use of nonsteroidal antiinflammatory drugs.
 Dry cough occurs in 15% of patients, and angioedema
occurs in <1% of patients taking ACE inhibitors.
 Angioedema occurs most commonly in individuals of
Asian origin and more commonly in African Americans
than in Caucasians.
 Hyperkalemia due to hypoaldosteronism is an
occasional side effect of both ACE inhibitors and
angiotensin receptor blockers.

ACE INHIBITORS
Captopril – oral: 25 mg, 50 mg tablets
 Enalapril – oral: 5, 10, 20 mg tablets
•Parenteral: 1.25 mg enalaprilat/ml
 Benazepril
 Fosinopril
 Lisinopril
 Moexipril
 Perindopril
 Quinapril
 Ramipril
 Trandolapril

ALDOSTERONE ANTAGONISTS
Spironolactone is a nonselective aldosterone antagonist
that may be used alone or in combination with a
thiazide diuretic.
 It may be a particularly effective agent in patients with
low-renin essential hypertension, resistant
hypertension, and primary aldosteronism.
 In patients with CHF, low-dose spironolactone reduces
mortality and hospitalizations for heart failure when
given in addition to conventional therapy with ACE
inhibitors, digoxin, and loop diuretics.

ALDOSTERONE ANTAGONISTS
 Because
spironolactone binds to progesterone
and androgen receptors, side effects may
include gynecomastia, impotence, and
menstrual abnormalities.
 These
side effects are circumvented by a newer
agent, eplerenone, which is a selective
aldosterone antagonist.
BETA BLOCKERS
Adrenergic receptor blockers lower blood pressure by
decreasing cardiac output, due to a reduction of heart
rate and contractility.
 Other proposed mechanisms by which beta blockers
lower blood pressure include a central nervous system
effect, and inhibition of renin release.
 Beta blockers are particularly effective in hypertensive
patients with tachycardia, and their hypotensive
potency is enhanced by coadministration with a
diuretic.
 In lower doses, some beta blockers selectively inhibit
cardiac receptors and have less influence on receptors
on bronchial and vascular smooth muscle cells;
however, there seems to be no difference in the
antihypertensive potencies of cardio-selective and nonselective beta blockers.

BETA BLOCKERS
Certain beta blockers have intrinsic sympathomimetic
activity, and it is uncertain whether this constitutes an
overall advantage or disadvantage in cardiac therapy.
 Beta blockers without intrinsic sympathomimetic
activity decrease the rate of sudden death, overall
mortality, and recurrent myocardial infarction.
 In patients with CHF, beta blockers have been shown to
reduce the risks of hospitalization and mortality.
Carvedilol and labetalol block both receptors and
peripheral -adrenergic receptors.
 The potential advantages of combined adrenergic
blockade in treating hypertension remain to be
determined.

BETA BLOCKERS
Propanolol – oral: 10, 20, 40, 60, 80 90 mg tab
4-8 mg/mL oral solution; Intensol 80 mg/mL
sol
Oral sustained-release: 60, 80, 120, 160 mg
cap
Parenteral: 1mg/mL for injection
 Metoprolol – oral: 50, 100 mg tab
Oral sustained-release: 25, 50, 100, 200 mg tab
Parenteral: 1mg/mL for injection
 Nadolol, Carteolol, Atenolol, Betalol, Bioprolol
 Pindolol, Acebutolol, Penbutolol
 Labetalol, Carvedilol

ADRENERGIC BLOCKERS



Postsynaptic, selective adrenoreceptor antagonists
lower blood pressure by decreasing peripheral vascular
resistance.
They are effective antihypertensive agents, used either
as monotherapy or in combination with other agents.
However, in clinical trials of hypertensive patients,
alpha blockade has not been shown to reduce
cardiovascular morbidity and mortality or to provide as
much protection against CHF as other classes of
antihypertensive agents.
ADRENERGIC BLOCKERS
 These
agents are also effective in treating lower
urinary tract symptoms in men with prostatic
hypertrophy.
 Nonselective
-adrenoreceptor antagonists bind
to postsynaptic and presynaptic receptors and
are primarily used for the management of
patients with pheochromocytoma.
SYMPATHOLYTIC AGENTS
 Centrally
acting sympathetic agonists decrease
peripheral resistance by inhibiting sympathetic
outflow.
 They may be particularly useful in patients with
autonomic neuropathy who have wide variations
in blood pressure due to baroreceptor
denervation.
 Drawbacks include somnolence, dry mouth, and
rebound hypertension on withdrawal.
SYMPATHOLYTIC AGENTS
 Peripheral
sympatholytics decrease peripheral
resistance and venous constriction by depleting
nerve terminal norepinephrine.
 Although potentially effective antihypertensive
agents, their usefulness is limited by orthostatic
hypotension, sexual dysfunction, and numerous
drug-drug interactions.
CALCIUM CHANNEL BLOCKERS
 Calcium
antagonists reduce vascular resistance
through L-channel blockade, which reduces
intracellular calcium and blunts
vasoconstriction.
 This
is a heterogeneous group of agents that
includes drugs in the following three classes:
phenylalkylamines (verapamil),
benzothiazepines (diltiazem), and 1,4dihydropyridines (nifedipine-like).
CALCIUM CHANNEL BLOCKERS
 Used
alone and in combination with other
agents (ACE inhibitors, beta blockers,
adrenergic blockers), calcium antagonists
effectively lower blood pressure; however, it is
unclear if adding a diuretic to a calcium blocker
results in a further lowering of blood pressure.
 Side
effects of flushing, headache, and edema
with dihydropyridine use are related to their
potencies as arteriolar dilators; edema is due to
an increase in transcapillary pressure
gradients, not to net salt and water retention.
DIRECT VASODILATORS
 These
agents decrease peripheral resistance
and concomitantly activate mechanisms that
defend arterial pressure, notably the
sympathetic nervous system, the reninangiotensin-aldosterone system, and sodium
retention.
 Usually, they are not considered first-line
agents but are most effective when added to a
combination that includes a diuretic and a beta
blocker.
DIRECT VASODILATORS
 Hydralazine
is a potent direct vasodilator that
has antioxidant and nitric-oxide enhancing
actions, and minoxidil is a particularly potent
agent and is most frequently used in patients
with renal insufficiency who are refractory to all
other drugs.
 Hydralazine
may induce a lupus-like syndrome,
and side effects of minoxidil include
hypertrichosis and pericardial effusion
CHOICE OF ANTIHYPERTENSIVE DRUG BASED ON
PATIENT CHARACTERISTICS
 Diabetic
patients and those with chronic
kidney disease: use ace inhibitors or
angiotensin II to delay nephropathy.
 Young
patients : use beta blockers
 Coronary
artey disease patients : use beta
blockers, Ca- antagonists. Avoid hydralazine.
 Heart
failure patients : use ACE-inhibitors
and/or diuretics. Generally avoid beta blockers
and Ca-antagonists.
CHOICE OF ANTIHYPERTENSIVE DRUG BASED ON
PATIENT CHARACTERISTICS
 Athletes
: Avoid beta blockers and diuretics.
 Broncho-pulmonary
disease patients : Use
verapamil and other Ca-antagonists. Avoid
beta blockers.
 Peripheral
Vascular disease patients : Use
calcium-antagonists, vasodilators, or ACEinhibitors. Avoid beta blockers.
 Dyslipidemic
diuretics.
patient : Avoid beta blockers and
CHOICE OF ANTIHYPERTENSIVE DRUG BASED ON
PATIENT CHARACTERISTICS
 End
stage renal disease patients : use Caantagonist, diuretics and centrally acting
agents. Caution on ACE- inhibitors.
 For
stroke patient : Use ACE-inhibitors and/or
diuretics.
 Elderly
patients : Use diuretics. Generally use
lower dosages.
FOLLOWUP AND MONITORING:
Once antihypertensive drug therapy is initiated, most
patients should return for followup and adjustment of
medications at monthly intervals or until the BP goal
is reached.
 More frequent visits will be necessary for patients with
stage 2 hypertension or with complicating comorbid
conditions.
 Serum potassium and creatinine should be monitored
at least one to two times per year.
 After BP is at goal and stable, followup visits can
usually be at 3- to 6-month intervals.

FOLLOWUP AND MONITORING:



Comorbidities such as HF, associated diseases such as
diabetes, and the need for laboratory tests influence
the frequency of visits.
Other cardiovascular risk factors should be monitored
and treated to their respective goals, and tobacco
avoidance must be promoted vigorously.
Low dose aspirin therapy should be considered only
when BP is controlled because of the increased risk of
hemorrhagic stroke when the hypertension is not
controlled.
BENEFITS OF LOWERING BLOOD
PRESSURE
 In
clinical trials, antihypertensive therapy
has been associated with reductions in
(1) stroke incidence averaging 35–40 percent
(2) myocardial infarction (MI), averaging 20–25
percent
(3) HF, averaging >50 percent
BENEFITS OF LOWERING BLOOD
PRESSURE
 It
is estimated that in patients with stage 1
hypertension (SBP 140–159 mmHg and/or DBP
90–99 mmHg) and additional cardiovascular
risk factors, achieving a sustained 12 mmHg
reduction in SBP over 10 years will prevent 1
death for every 11 patients treated.
 In
the added presence of CVD or target organ
damage, only nine patients would require such
BP reduction to prevent one death.
RESISTANT HYPERTENSION
 Refers
to patients with blood pressures
persistently >140/90 mmHg despite taking
three or more antihypertensive agents,
including a diuretic, in reasonable combination
and at full doses.
 Resistant
or difficult-to-control hypertension is
more common in patients >60 years than in
younger patients.
CAUSES OF RESISTANT HYPERTENSION


Improper Blood Pressure Measurement
Volume overload
 Excess sodium intake
 Volume retention from kidney disease
 Inadequate diuretic therapy
CAUSES OF RESISTANT HYPERTENSION


Drug-induced or other causes
 Nonadherence
 Inadequate doses
 Inappropriate combinations
 Nonsteroidal anti-inflammatory drugs; cyclooxygenase 2
inhibitors
 Cocaine, amphetamines, other illicit drugs
 Sympathomimetics (decongestants, anorectics)
 Oral contraceptive hormones
 Adrenal steroid hormones
 Cyclosporine and tacrolimus
 Erythropoietin
 Licorice (including some chewing tobacco)
 Selected over-the-counter dietary supplements and medicines
(e.g., ephedra, ma huang, bitter orange)
Associated conditions
 Obesity
ORTHOSTATIC HYPOTENSION
BP measurements are typically recorded in the sitting
position.
 This practice, while convenient for the practitioner,
limits the ability to diagnose OH.
 Normally, standing is accompanied by a small increase
in DBP and a small decrease in SBP when compared to
supine values.
 OH is present when there is a supine-to-standing BP
decrease >20 mmHg systolic or >10 mmHg diastolic.

ORTHOSTATIC HYPOTENSION
There is more OH in diabetic individuals.
 There is a strong correlation between the severity of OH
and premature death as well as increased incidents of
falls and fractures.
 The causes of OH include severe volume depletion,
baroreflex dysfunction, autonomicinsufficiency, and
certain venodilator antihypertensive drugs, especially
alpha blockers and alpha-beta blockers.
 Diuretics and nitrates may further aggravate OH.

ORTHOSTATIC HYPOTENSION
In treating older hypertensive patients, clinicians should
be alert to potential OH symptoms such as postural
unsteadiness, dizziness, or even fainting.
 Lying and standing BPs should be obtained periodically
in all hypertensive individuals over age 50.
 OH is a common barrier to intensive BP control that
should be clearly documented; if present, drug therapy
should be adjusted accordingly and appropriate
warnings given to patients.

HYPERTENSIVE CRISES: EMERGENCIES AND
URGENCIES



Hypertensive emergencies are characterized by
severe elevations in BP (>180/120 mmHg) complicated
by evidence of impending or progressive target organ
dysfunction.
They require immediate BP reduction (not necessarily to
normal) to prevent or limit target organ damage.
Examples include hypertensive encephalopathy,
intracerebral hemorrhage, acute MI, acute left
ventricular failure with pulmonary edema, unstable
angina pectoris, dissecting aortic aneurysm, or
eclampsia.
HYPERTENSIVE CRISES: EMERGENCIES AND
URGENCIES
Hypertensive urgencies are those situations
associated with severe elevations in BP without
progressive target organ dysfunction.
 Examples include upper levels of stage II hypertension
associated with severe headache, shortness of breath,
epistaxis, or severe anxiety.
 Majority of these patients present as noncompliant or
inadequately treated hypertensive individuals, often
with little or no evidence of target organ damage.
 Early triage to establish the appropriate therapeutic
strategies for these patients is critical to limiting
morbidity and mortality.

HYPERTENSIVE CRISES: EMERGENCIES AND
URGENCIES
Patients with hypertensive emergencies should be
admitted to an intensive care unit for continuous
monitoring of BP and parenteral administration of an
appropriate agent.
 The initial goal of therapy in hypertensive emergencies
is to reduce mean arterial BP by no more than 25
percent (within minutes to 1 hour), then if stable, to
160/100–110 mmHg within the next 2–6 hours.
 Excessive falls in pressure that may precipitate renal,
cerebral, or coronary ischemia should be avoided.
 For this reason, short-acting nifedipine is no longer
considered acceptable in the initial treatment of
hypertensive emergencies or urgencies.

HYPERTENSIVE CRISES: EMERGENCIES AND
URGENCIES
If this level of BP is well tolerated and the patient is
clinically stable, further gradual reductions toward a
normal BP can be implemented in the next 24–48 hours.
 Exceptions to the above recommendation
 Patients with an ischemic stroke in which there is no
clear evidence from clinical trials to support the use of
immediate antihypertensive treatment
 patients with aortic dissection who should have their
SBP lowered to <100 mmHg if tolerated
 patients in whom BP is lowered to enable the use of
thrombolytic agents.

HYPERTENSIVE CRISES: EMERGENCIES AND
URGENCIES
Some patients with hypertensive urgencies may benefit
from treatment with an oral, short-acting agent such as
captopril, labetalol, or clonidine followed by several
hours of observation.
 However, there is no evidence to suggest that failure to
aggressively lower BP in the ER is associated with any
increased short-term risk to the patient who presents
with severe hypertension.
 Such a patient may also benefit from adjustment in their
antihypertensive therapy, particularly the use of
combination drugs, or reinstitution of medications if
noncompliance is a problem.

HYPERTENSIVE CRISES: EMERGENCIES AND
URGENCIES



Most importantly, patients should not leave the ER
without a confirmed follow up visit within several days.
Unfortunately, the term “urgency” has led to overly
aggressive management of many patients with severe,
uncomplicated hypertension.
Oral loading doses of antihypertensive agents can lead to
cumulative effects causing hypotension.
PREVENTION



Primary - measures include activities that help avoid
hypertension
 Example : avoid fatty foods or exercise daily like
atleast
30 minutes walking
Secondary - identify and treat asymptomatic persons
who have already developed risk factors or preclinical
disease but in whom the condition is not clinically
apparent
 Example : early case finding and screening tests
Tertiary - activities involve the care of established
disease, with attempts made to restore to highest
function, minimize the negative effects of disease, and
prevent disease-related complications