hypertension is a condition arrising due to increased symphathetic tone so drugs therapies are administered for minimising disease sevearity and further complications. Drug therapy includes drugs like alpha blockers, beta blockers, ACE INHIBITORS, ARBs, vasodilators,direct renin inhibitors, reserpine,prostaglandin analogs, calcium channel blockers for minimising excessive pressure and increased contractility of the heart.

1. Pharmacotherapy of
HTN
Dr. Chavan P. R
Pharm D

2. ACEI
 Blocks
conversion of AI
to AII
 Blocks
degradation of
bradykinin,
 prostaglandin
E2 and
prostacyclin

3.  Starting doses of ACE inhibitors should be
low with slow dose titration.
 Acute hypotension- sodium- or volume-
depleted, in heart failure exacerbation, very
elderly, or on concurrent vasodilators or
diuretics.
 once daily for hypertension except captopril
(2-3 day)
 captopril absorption is reduced by 30% to
40% when given with food.

4.  Decrease aldosterone and can increase
serum potassium concentrations
 Hyperkalemia occurs primarily in patients
with chronic kidney disease or diabetes
and in those also taking ARBs, NSAIDs,
potassium supplements, or potassium-
sparing diuretics

5.  GFR decreases
 Angioedema - Drug withdrawal
 ADR- persistent dry cough
 contraindicated in pregnancy

6. Angiotensin II Receptor Blockers
 Angiotensin II is
generated by the
renin-angiotensin
pathway or by
Chymases
 ARBs antagonize
angiotensin II
 Block the
angiotensin type 1
receptor
 Do not block the
breakdown of
bradykinin

7.  Type 2 diabetes and nephropathy, ARB
therapy significantly reduce progression of
nephropathy.
 For patients with LV dysfunction, ARB
therapy has also been shown to reduce
the risk of cv events when added to a
stable regimen of a diuretic, ace inhibitor,
and β blocker or as alternative therapy in
ace inhibitor-intolerant patients.

8.  ADR-
Renal insufficiency,
hyperkalemia,
orthostatic hypotension
Angioedema
 Contraindication - pregnancy

9. α 1-Receptor Blockers
 Inhibit catecholamine uptake in smooth
muscle cells of the peripheral vasculature,
resulting in vasodilation
 ADRs
 transient dizziness or faintness,
 palpitations, and
 even syncope
 orthostatic dizziness
 Sodium and water retention

11.  Doxazosin-alternative agents for unique
situations, such as men with benign
prostatic hyperplasia
 For HTN- in combination with primary
antihypertensive agents

12. B blocker
 Decreased cardiac output through negative
chronotropic and inotropic effects on the heart
and
 Inhibition of renin release from the kidney
 Atenolol, betaxolol, bisoprolol, and metoprolol
are cardioselective at low doses, the effect is lost
at higher doses
 Acebutolol, carteolol, penbutolol, and pindolol
possess intrinsic sympathomimetic activity (ISA)
or partial β -receptor agonist activity.

13.  Propranolol and metoprolol undergo
extensive first-pass metabolism
 Atenolol and nadolol have relatively long
half-lives and are excreted renally
 dosage may need to be reduced in
patients with moderate to severe renal
insufficiency

14.  β -blockade in the myocardium include
bradycardia, AV conduction abnormalities,
and acute heart failure
 Blocking β 2-receptors in arteriolar
smooth muscle may cause cold
extremities and aggravate PAD or
Raynaud’s phenomenon because of
decreased peripheral blood flow.

15.  Abrupt cessation of β -blocker therapy may
produce unstable angina, MI, or even death
in patients with coronary disease
 In patients without heart disease, abrupt
discontinuation of β -blockers may be
associated with tachycardia, sweating, and
generalized malaise in addition to increased
BP.
 β -Blockers increase serum triglyceride levels
and decrease high-density lipoprotein
cholesterol levels slightly.

16. Calcium channel blocker

17.  Relaxation of cardiac and smooth muscle
by blocking voltagesensitive calcium
channels
 Verapamil decreases heart rate, slows
atrioventricular (AV) nodal conduction,
and produces a negative inotropic effect
that may precipitate heart failure in
patients with borderline cardiac reserve.
 Diltiazem decreases AV conduction and
heart rate to a lesser extent than
verapamil

18. ADRs
 bradycardia,
 AV block,
 heart failure
 anorexia,
 nausea,
 peripheral edema,
 hypotension
 constipation

19.  Dihydropyridines cause a baroreceptor-
mediated reflex increase in heart rate
because of their potent peripheral
vasodilating effects.
 Dihydropyridines do not decrease AV node
conduction and are not effective for
treating supraventricular
tachyarrhythmias.

20. Adverse effects of
dihydrophyridines
 acute hypotension
 dizziness,
 flushing,
 headache,
 gingival hyperplasia,
 peripheral edema

21. Centrally a2 agonist
 Clonidine, guanabenz, guanfacine, and
methyldopa
 Stimulating α 2-adrenergic receptors in
the brain, which reduces sympathetic
outflow from the vasomotor center and
increases vagal tone
 Decreases in heart rate, cardiac output,
total peripheral resistance, plasma renin
activity, and baroreceptor reflexes.

23. ADRs
 Depression,
 Orthostatic hypotension,
 Dizziness,
 Anticholinergic effects.
 Chronic use- sodium and fluid retention
 Abrupt cessation may lead to rebound
hypertension
 Methyldopa rarely may cause hepatitis or
hemolytic anemia.

24. Postganglionic Sympathetic
Inhibitors
 Guanethidine and guanadrel deplete
norepinephrine from postganglionic
sympathetic nerve terminals and inhibit
the release of norepinephrine in response
to sympathetic nerve stimulation.
 This reduces cardiac output and
peripheral vascular resistance.

25. Direct Renin Inhibitor
 Aliskiren blocks the renin-angiotensin-
aldosterone system at its point of a activation,
which results in reduced plasma renin activity
and BP. It provides BP reductions comparable to
an ACE inhibitor, ARB, or CCB.
 It also has additive antihypertensive effects
when used in combination with thiazides, ACE
inhibitors, ARBs, or CCBs.
 It is approved for monotherapy or in combination
with other agents.
 contraindication - pregnancy.

26. ADRs
 Orthostatic hypotension
 erectile dysfunction,
 diarrhea, and
 weight gain.

27. Reserpine

28.  Reserpine depletes norepinephrine from
sympathetic nerve endings
 This reduces sympathetic tone, decreasing
peripheral vascular resistance and BP.
 Reserpine has a long half-life that allows for
once-daily dosing, but it may take 2 to 6
weeks before the maximal antihypertensive
effect is seen.
 Reserpine can cause significant sodium and
fluid retention, and it should be given with a
diuretic (preferably a thiazide).

29. ADRs
Due to increased parasympathetic tone
 nasal stuffiness,
 increased gastric acid secretion,
 diarrhea, and
 bradycardia.
 The most serious side effect is dose-related
mental depression resulting from CNS depletion
of catecholamines and serotonin. This can be
minimized by not exceeding 0.25 mg daily

30. Direct Arterial Vasodilators

31. ADRs
 Lupus-like syndrome,
 Dermatitis,
 Drug fever,
 Peripheral neuropathy,
 Hepatitis, and vascular headaches.
 Hypertrichosis on the face, arms, back,
and chest