PHARMACOTHERAPY OF

HYPERTENSION

Y7PH0566,
YEDLA PRADEEP KUMAR,
4TH B.PHARMACY,
CIPS,LAM,
GUNTUR.
 CONTENTS
• KNOWING THE TITLE • PHARMACOTHERAPY OF
• STAGES OF HYPERTENSION
HYPERTENSION • INDIVIDUAL CLASSES OF
• ETIOLOGY OF DRUGS
HYPERTENSION • DRUG SELECTION
• COMPLICATIONS OF • COMBINATIONAL
HYPERTENSION THERAPY
• HISTORY OF • THERAPY TO SPECIAL
HYPERTENSION POPULATIONS
TREATMENT • CHRONOTHERAPEUTICS
• TREATMENT OF IN THE TREATMENT OF
HYPERTENSION HYPERTENSION
• NON-PHARMACOLOGIC • EVALUATION OF
THERAPY THERAPUTIC OUTCOMES
• REFERENCES
KNOWING THE TITLE……………...

Pharmacotherapy refers to the treatment of disease by the use of drugs.

As per the Seventh Report of the Joint National Committee on

Prevention, Detection, Evaluation, and Treatment of High Blood
Pressure, Hypertension is a sustained systolic blood pressure (SBP)
≥140 mm Hg (or)diastolic blood pressure (DBP) ≥90 mm Hg.
STAGES OF HYPERTENSION

 Normal <120 and <80

 Pre hypertension 120–139 or 80–89

 Stage 1 Hypertension 140–159 or 90–99

 Stage 2 Hypertension ≥160 or ≥100
 ETIOLOGY OF HYPERTENSION
o Dyslipidemia
o Cigarette smoking
o Obesity (BMI ≥30 kg/m2)
o Physical inactivity
o Diabetes mellitus
o Estimated GFR <60 ml/min
o Family history of premature cardiovascular
disease(men <55 years or women <65 years)
 COMPLICATIONS
OF HYPERTENSION
● Heart (left ventricular hypertrophy, angina or prior
myocardial infarction, prior coronary revascularization,
or heart failure)
● Brain (stroke or transient ischemic attack)
● Chronic kidney disease
● Peripheral arterial disease
● Retinopathy
HISTORY OF HYPERTENSION TREATMENT
 The Yellow Emperor’s Classic of Internal Medicine-“The heart
influences the force which fills the pulse with blood. If too much salt
is eaten in food, the pulse hardens.”
 Chinese and Arabic cultures-overeating and over excitability were
harmful
 (1897)Tigerstedt and Bergman discovered a pressor protein in the
kidney, which they called renin
 (1900)Treupel and Edinger-Sodium thiocyanate
 (1931)P.D. WhITE-“Hypertension may be an important compensatory
mechanism which should not be tampered with even were it certain
that we could control it.”
 Beyer and Sprague- Chlorothiazide
 Ser-Ap-Es -A fixed-dose combination of reserpine, hydralazine, and
Chlorothiazide most widelyin the 1960s to 1980
 TREATMENT OF
HYPERTENSION
INDIVIDUALISED CARE PHARMACOTHERAPY
• Non-pharmacological • Decrease extracellular volume-
treatment diuretics
• Diet regulation • Inhibit renin release-beta blockers
• Life style • Decrease aldosterone secretion
modifications o Inhibit AT-II formation-ACE inhibitors
o Antagonize AT-II receptor activity- AT-
II receptor antagonists
• Smooth muscle relaxation-Ca+2
channel blockers, alpha adrenoceptor
blockers
• Vasodilation-hydralazine,minoxidil
 NON-PHARMACOLOGIC
THERAPY
• Adoption of the Dietary Approaches to
Stop Hypertension (DASH) eating plan,
• dietary sodium restriction to less than or
equal to 2.4 g/day (6 g/day sodium
chloride),
• moderate alcohol consumption (less than
or equal to 1 oz ethanol per day), and
• Patients diagnosed with stage 1 or 2
hypertension should be placed on lifestyle
modifications and drug therapy
concurrently
• regular aerobic physical activity,
• weight reduction if overweight,
• smoking cessation.
 PHARMACOTHERAPY
OF HYPERTENSION
BETA BLOCKERS ACE INHIBITORS
DIURETICS
(Atenolol, (captopril,
(thiazide, loop) labetalol) Enlapril)

ANGIOTENSIN II Ca+2CHANNEL ALPHA

RECEPTOR BLOCKERS ADRENOCEPTOR
ANTAGONISTS (Nifedipine, BLOCKERS
(Losartan) verapamil) (Prazosin, tetrazosin)

Miscellaneous
(clonidine,
hydralazine,
reserpine)
 INDIVIDUAL CLASSES
DIURETICS: OF DRUGS
a. Thiazides are the preferred type of diuretics for treating hypertension, are
effective in lowering blood pressure.
b. However, as renal function declines, sodium and fluid accumulate, and the
use of a more potent loop diuretic is necessary
c. Potassium-sparing diuretics are weak antihypertensives when used alone but
provide an additive hypotensive effect when combined with thiazide or loop
diuretics.
BETA BLOCKERS:
Atenolol, betaxolol, bisoprolol, and metoprolol are cardio selective at low doses
and may be safer than nonselective blockers in patients with asthma, chronic
obstructive pulmonary disease (COPD), diabetes, and peripheral arterial
disease.
ACE INHIBITORS:
d. Enlapril(or)lisnopril are generally preferred.
e. All ACE inhibitors can be dosed once daily for hypertension except captopril,
which is usually dosed 2 or 3 times daily. The absorption of captopril is
reduced by 30% to 40% when given with food.
AT-II RECEPTOR ANTAGONISTS:
a. Losartan is prototype drug
b. Used for patients intolerable to ACE inhibitors
Ca+2 CHANNEL BLOCKERS:
c. Verapamil decreases heart rate, slows AV nodal conduction, and produces a
negative ionotropic effect that may precipitate heart failure.
d. Diltiazem decreases AV conduction and heart rate to a lesser extent than verapamil.
e. Nifedipine, nicadipine, amlodipine have a high affinity for Ca+2 vascular channels.
ALPHA BLOCKERS:
f. Prazosin, terazosin, and doxazosin are selective receptor blockers.
g. Mild to moderate hypertension treatment.
MISCELLANEOUS:
• Includes centrally acting drugs and vasodilators and reserpine
a. Clonidine, guanabenz, guanfacine, and methyldopa lower blood pressure primarily
by stimulating adrenergic receptors in the brain, decreases heart rate, cardiac
output, total peripheral resistance, plasma renin activity, and baroreceptor reflexes.
b. Hydralazine and minoxidil cause direct arteriolar smooth muscle relaxation.
Minoxidil is a more potent vasodilator than hydralazine.
c. Reserpine depletes norepinephrine from sympathetic nerve endings ,this reduces
sympathetic tone, decreasing peripheral vascular resistance and blood pressure.
 DRUG SELECTION
Generally drugs are selected based on the severity of
the disease and underlying complications.
1ST LINE DRUGS: DIURETICS/BETA BLOCKERS
2ND LINE DRUGS: DIURETICS/BETA
BLOCKERS+VASODILATORS/ACE INHIBITORS
3RD LINE DRUGS: METHYLDOPA, CLONIDINE,
ADRENARGIC NEURONE BLOCKERS
4TH LINE DRUGS: MINOXIDIL/ HYDRALAZINE /
DIAZOXIDE
Numerous
drugs
Treatment algorithms
 COMBINATIONAL THERAPY
Cases where combinational therapy is preferred
over monotherapy

 To improve the responsiveness of cells to drugs

 To potentiate the action of drugs
 To treat severe stages of disease
 To minimize complications
 DRUGS WHICH CAN BE
COMBINED

• Diuretics/vasodilators/ca+2 channel blockers/ACE

inhibitors +
Beta blockers/clonidine/methyl dopa
• Sympatholytics + diuretics
• Hydralazine/dihydropyridine + Beta blockers
• ACE inhibitors/ AT-II receptor antagonists
+
diuretics
 DRUGS WHICH CANNOT BE
COMBINED

• Alpha/beta blockers + clonidine

• Nifedipine + diuretics
• Hydralazine + dihydropyridine/Prazosin
• Verapamil/dilteazem + beta blockers
• Methyldopa + clonidine
 THERAPY TO SPECIAL POPULATIONS
Includes therapy to
• Older People
• Children and Adolescents
• Pregnancy
• African Americans
• Hypertension associated with other complications
--Pulmonary Disease and Peripheral Arterial Disease
--Dyslipidemia
• Hypertensive urgencies and emergencies
 OLDER PEOPLE
• Elderly patients may present with either isolated systolic
hypertension or an elevation in both SBP and DBP.
• Elderly patients are usually more sensitive to volume depletion
and sympathetic inhibition, and treatment generally should be
initiated with a small dose of a diuretic (e.g.,
hydrochlorothiazide, 12.5 mg) and increased gradually.
• If a diuretic alone does not achieve the desired action an ACE
inhibitor can be added at low doses with gradual increases.
• Alpha Blockers are the first drugs of choice in elderly patients
with both hypertension and angina, and
• ACE inhibitors are strongly preferred for hypertensive patients
with diabetes or heart failure.
 CHILDREN
AND ADOLESCENTS
• secondary hypertension(e.g., pyelonephritis,
glomerulonephritis, renal artery stenosis, renal cysts) is much
more common in children than in adults.
• Management of the underlying disorder usually restores normal
blood pressure.
• Diuretics, Alpha blockers, and ACE inhibitors are very effective.
• ACE inhibitors and ARBs are contraindicated in sexually active
girls because of potential teratogenic effect and in those who
might have bilateral renal artery stenosis or unilateral stenosis
in a single kidney.
• Long-acting dihydropyridine can been used in children.
 PREGNANCY

• Most commonly used drug is intravenous hydralazine;

intravenous labetalol is also effective.
• Chronic hypertension occurs before 20 weeks' gestation.
Methyldopa is considered the drug of choice .
• labetalol, and CCBs are also reasonable alternatives.
• ACE inhibitors and ARBs are absolutely
contraindicated(foetopathic)
• Reserpine-suicidal tendencies
 AFRICAN AMERICANS
• Hypertension is more common and more severe in black
persons than in those of other races.
• Differences in electrolyte homeostasis, glomerular filtration rate,
sodium excretion and transport mechanisms, plasma renin
activity, and blood pressure response to plasma volume
expansion have been noted.
• Thiazide diuretics are first-line therapy for most patients, and
CCBs are also particularly effective.
• Addition of a ACE inhibitor, or ARB to a thiazide diuretic or CCB
significantly increases the antihypertensive response.
HYPERTENSION ASSOCIATED WITH OTHER
COMPLICATIONS
• Nonselective alpha blockers should be avoided in hypertensive
patients with asthma, COPD, and peripheral vascular disease.
• carvedilol and labetalol may be used in peripheral arterial disease
.However, they should be avoided in patients with asthma or COPD.
• Dyslipidemia is a major cardiovascular risk factor, and it should be
controlled in hypertensive patients.
• Thiazide diuretics and alpha blockers affect serum lipids adversely,
but these effects generally are transient and of no clinical
consequence.
• The beta blockers have favorable effects (decreased low-density
lipoprotein cholesterol and increased high-density lipoprotein
cholesterol levels). Because they do not reduce cardiovascular risk
as effectively as thiazide diuretics, this benefit is not clinically
applicable.
 HYPERTENSIVE URGENCIES AND
EMERGENCIES
• Hypertensive urgencies are managed by adjusting maintenance
therapy by adding a new antihypertensive and/or increasing the
dose of a present medication.
• Acute administration of a short-acting oral drug (captopril,
clonidine, or labetalol) is an option.
• Oral captopril doses of 25 to 50 mg may be given at 1- to 2-
hour intervals. The onset of action is 15 to 30 minutes.
• For treatment of hypertensive rebound after withdrawal of
clonidine, 0.2 mg is given initially, followed by 0.2 mg hourly
until the DBP falls below 110 mm Hg or a total of 0.7 mg has
been administered; a single dose may be sufficient.
• Labetalol can be given in a dose of 200 to 400 mg, followed
by additional doses every 2 to 3 hours.
• Hypertensive emergencies require immediate blood pressure
reduction
• The goal is not to lower blood pressure to normal instead, a
reduction in mean arterial pressure (MAP) of up to 25% within
minutes to hours is the initial target.
• If blood pressure is then stable, it can be reduced toward
160/100 mm Hg within the next 2 to 6 hours.
• If blood pressure reduction is well tolerated, additional gradual
decrease toward the goal blood pressure can be attempted
after 24 to 48 hours.
• Precipitous drops in blood pressure may cause end-organ
ischemia or infarction.
• Nitroprusside,nitroglycerine,nicadipine,labetalol,hydralazine can
be used.
 CHRONOTHERAPEUTICS IN THE TREATMENT OF
HYPERTENSION
MEDICATION DOSE DOSING TIMES EFFECT
BenazepriL 10 9 A.M. vs. 9 P.M. 9 A.M. dose exerts
greater BP-lowering
effect than 9 P.M.
dosing.

Ramipril 2.5 8 A.M. vs. 8 P.M. 8 P.M. dosing

improves nocturnal
BP-lowering effect.

Diltiazem 100–200 8 A.M. vs. 7 P.M. 8 A.M. dosing better

reduces BP during
nighttime sleep; 8
P.M. dosing exerts
greater daytime BP-
lowering effect and
inhibition of
morning BP rise.
 EVALUATION OF
THERAPEUTIC OUTCOMES
•The goal of antihypertensive treatment is to maintain arterial blood
pressure below 140/90 mm Hg.
•Lowering blood pressure to less than 130/80 mm Hg should be
targeted in patients with diabetes or chronic kidney disease.
• Readings should be taken 2 to 4 weeks after initiating or making
changes in therapy. Once this goal level is achieved, readings need to
be evaluated only every 3 to 6 months in asymptomatic patients.
•A careful history should be taken for chest pain, palpitations, dizziness,
slurred speech, and loss of balance to assess the likelihood of
cardiovascular and cerebrovascular hypertensive complications.
•Patient compliance with the therapeutic regimen should be assessed
regularly.
•They should be questioned periodically about changes in their general
health
•Patients should be monitored routinely for adverse drug effects.
CONCLUSION
 REFERENCES
PHARMACOTHERAPY HANDBOOK,
6TH EDITION BY WELLS, BARBARA G.;
DIPIRO, JOSEPH T.;
SCHWINGHAMMER, TERRY L.;
HAMILTON,
CINDY W

HYPERTENSION: A COMPANION TO
BRENNER AND RECTOR’S THE KIDNEY
BY Suzanne Oparil, M.D.
Michael A.Weber, M.D.

LIPINCOTT’S PHARMACOLOGY 4TH

EDITION BY RICHARD
A.HARVEY,PPAMELA C.CHAMPE

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