Antihypertensive

drugs
Dr Kumar
Dept of Pharmacology

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 HYPERTENSION
• Hypertension- elevation of systolic and/ or diastolic
BP above 140/90 mm of Hg.

• Blood pressure- determined by cardiac output (CO)

and total peripheral vascular resistance (PVR).

• Prolonged hypertension damages the blood vessels of

the heart, brain and kidneys.

• Complications- stroke, coronary artery disease

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 DIURETICS
• Diuretics enhance the excretion of sodium and water
resulting in

1. ↓ Plasma volume → ↓ cardiac output → ↓ BP

2. ↓ Body sodium → relaxation of vascular smooth

muscles (due to Na+ depletion in the vascular
smooth muscle) - ↓ PVR → ↓ BP.

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 DIURETICS
• Thiazides are the first-line antihypertensives.

• Initial dose- 12.5 mg daily hydrochlorothiazide.

• If the response is not adequate the dose may be

increased to a maximum of 25 mg daily.

• They may be combined with a K+ sparing diuretic

which is the best way to avoid hypokalaemia-1.25 mg
amiloride with 12.5 mg hydrochlo-rothiazide.
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RAAS
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 Angiotensin Converting Enzyme (ACE)
Inhibitors

• ACE inhibitors prevent the formation of angiotensin

II and (indirectly) aldosterone.

• There is vasodilation and decrease in PVR resulting

in a fall in BP.

• ACE also degrades bradykinin, ACE inhibitors raise

the bradykinin levels which is a potent vasodilator.

• This also contributes to the fall in BP.

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 Adverse effects
1. Persistent dry cough: due to ↑ bradykinin

2. Hypotension

3. Hyperkalaemia

4. Dysguesia–An altered taste sensation

5. Angioneurotic edema

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 Uses
1. Hypertension

• ACE inhibitors are presently the first line

antihypertensives.

• ACE inhibitors are useful in the treatment of

hypertension of all grades due to all causes.

• Addition of a diuretic potentiates their

antihypertensive efficacy.
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 Uses
2. CCF-ACE inhibitors are the first line drugs

3. Myocardial infarction: ACE inhibitors started

within 24 hours and given for several weeks prevent
the development of CCF and reduce mortality.

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 Uses
4. Coronary artery disease- In patients who are at a high
risk of ischaemic cardiovascular conditions like MI and
stroke, ACE inhibitors afford significant benefit by
reducing the risk of MI, stroke and sudden death.

5. Chronic renal failure- In patients with diabetic

nephropathy and chronic renal failure, ACE inhibitors
delay the progression of renal disease.

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 Angiotensin II Receptor Blockers
(ARBs)
• MOA- It block AT1 receptor.

• The main advantage of ARBs over ACE inhibitors is

that there is no increase in bradykinin levels and its
associated adverse effects like dry cough and
angioedema because angiotensin converting enzyme
is not inhibited.

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 Angiotensin II Receptor Blockers
(ARBs)
• ARBs - candesartan, irbesartan, valsartan, telmisartan

Uses

1. Hypertension- same as ACE-I

2. Cardiac failure

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 SYMPATHOLYTICS
Drugs Acting Centrally
• Clonidine is a selective α2 agonist. (autoreceptor)

• Stimulation of α2 receptors in the CNS, decreases

central sympathetic outflow, blocks the release of
noradrenaline from the nerve terminals leading to a
fall in BP and bradycardia.

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 Drugs Acting Centrally
• α-methyl dopa—an analog of dopa, is a prodrug.

• It is metabolised in the body to α-methyl

norepinephrine which is an α2 agonist and acts like
clonidine.

• α-methyl dopa is used in mild to moderate

hypertension along with a diuretic.

• It is safe in hypertension during pregnancy

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 Ganglion Blockers
Trimethaphan
• These drugs block both sympathetic and
parasympathetic ganglia resulting in decreased
sympathetic tone and a fall in BP.
• But they produce several side effects as they block
both sympathetic and parasympathetic ganglia and
are not used

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 Adrenergic Neuron Blockers
• Guanethidine depletes the stores of noradrenaline in
the adrenergic neurons and also blocks its release.

• Because of the adverse effects like postural

hypotension, diarrhoea and sexual dysfunction, it is
not used.

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 Adrenergic Receptor Blockers
• β-blockers - are mild antihypertensives.
• Blockade of cardiac β1 receptors results in decreased
myocardial contractility and cardiac output.
• Thus they reduce the BP due to a fall in the cardiac
output.
• They also lower plasma renin activity and have an
additional central antihypertensive action.

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• α-blockers - Nonselective α blockers like
phenoxybenzamine and phentolamine are used in the
treatment of hypertension due to pheochromocytoma.

• Selective α1 blockers like prazosin, terazosin and

doxazosin dilate both arterioles and venules.

• Peripheral vascular resistance is decreased leading to

a fall in BP with only mild tachycardia.
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• ‘First dose phenomenon’ can be avoided by starting
with a low dose prazosin (0.5 mg) given at bed time.

• Dose is gradually increased.

α and β-blockers:

• Labetalol and carvedilol block α1 and β receptors.

• It is used IV in the treatment of hypertension in

pheochromocytoma and in hypertensive emergencies.

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Calcium Channel
Blockers
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 Calcium Channel Blockers
• Nifedipine • Felodipine

• Nicardipine • Amlodipine

• Nimodipine • Isradipine

• Nitrendipine • Verapamil

• Nisoldipine • Diltiazem

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 MECHANISM OF ACTION
• The depolarisation of the cardiac and vascular smooth
muscle cells depend on the entry of extracellular
calcium into the cell through the calcium channels.

• Intracellular calcium is also increased by receptor

mediated action – i.e. agonist induced calcium
release.

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 MECHANISM OF ACTION
• This calcium triggers the release of intracellular
calcium from the sarcoplasmic reticulum.

• All these calcium ions bring about contraction of the

cardiac and vascular smooth muscle cells.

• Calcium channel antagonists inhibit the entry of

calcium by blocking the L-type of calcium channels.

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 PHARMACOLOGICAL ACTIONS

1. Vascular smooth muscle:

• Relaxation of the arteriolar smooth muscles-

reduced peripheral vascular resistance and blood
pressure.

• The effect on venous beds is not significant.

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 PHARMACOLOGICAL ACTIONS

2. Heart :

• Depress myocardial contractility,

• Reduce heart rate and

• Higher doses- slow AV conduction.

• Reduce cardiac work

• Myocardial oxygen consumption is reduced.

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 PHARMACOLOGICAL ACTIONS

3. Coronary circulation :

• CCBs dilate the coronary vessels, increasing the

coronary blood flow.

• Hence they are useful in variant angina.

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 Pharmacokinetics
• Well-absorbed
• But undergo extensive first pass metabolism.
• Highly plasma protein bound
• Metabolized in the liver.
Adverse effects:
• constipation, bradycardia, heart block, hypotension
and skin rashes.

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 Therapeutic Uses of CCBs
1. Angina pectoris –

• Prophylaxis in exertional angina- as they decrease

myocardial oxygen demand and bring about
coronary vasodilatation.

• variant angina- as they bring about coronary

vasodilation.

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 Therapeutic Uses of CCBs
2. Hypertension –

• Relaxation of the arteriolar smooth muscles-

reduced peripheral vascular resistance and blood
pressure.

3. Arrhythmias – Verapamil is used in PSVT and to

control ventricular rate in atrial flutter or fibrillation.

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 Therapeutic Uses of CCBs
4. Peripheral vascular disease (Raynaud’s disease)-

• for their vasodilator effects.

5. Migraine – Verapamil is useful in the prophylaxis of

migraine

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 Vasodilators
• Vasodilators relax the vascular smooth muscles thus
reducing BP due to decreased peripheral vascular
resistance.

• Hydralazine is a directly acting arteriolar dilator.

• Sodium nitroprusside- a rapidly acting vasodilator and it

relaxes both arterioles and venules.

• Both peripheral resistance and cardiac output are reduced

resulting in lower myocardial oxygen consumption.

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• Uses

1. Nitroprusside is the drug of choice in hypertensive

emergencies.

2. It is used in situations where short-term reduction of

myocardial work load is required as in myocardial
infarction.

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 Hypertensive emergencies
• Parenteral drugs are preferred.

• IV sodium nitroprusside under close monitoring is

the drug of choice (in some conditions BP should be
lowered gradually to avoid ischaemia to vital organs).

• IV esmolol, diazoxide and sublingual nifedipine are

alternatives.

• Hydralazine can also be used.

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• BP should be constantly monitored because drugs like
sodium nitroprusside can bring down BP suddenly
which results in hypoperfusion of vital organs.

• As soon as possible switch over to oral drugs.

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 Non-pharmacological measures
• Low salt diet,
• Exercise
• Weight reduction
• Meditation and yoga
• Smoking and alcohol should be given up.
• These measures also help in reducing the dose of the
antihypertensive needed.

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