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Anti-Hypertensive Agents
Hypertension: A sustained systolic blood pressure of 140mm Hg or higher or a sustained diastolic pressure of 90 mm Hg or
higher.

Primary (Essential) Hypertension: 95%

Secondary Hypertension: 5%

Factors associated with Primary Hypertension:

Obesity,
Sedentary life-style,
Excessive dietary sodium intake by individuals with salt sensitivity,
Excessive intake of alcohol,
Smoking, and stress.

Secondary hypertension is most often due to renal disease or endocrine abnormalities.

An estimated 50 million Americans have hypertension.

Four stages of hypertension, ranging from mild to very severe

Stage 1 - Systolic 140-159 or diastolic 90-99

Stage 2 - Systolic 160-179 or diastolic 100-109
Stage 3 - Systolic 180-209 or diastolic 110-119
Stage 4 - Systolic > 210 or diastolic > 120

Chronic hypertension damages blood vessels, accelerates atherosclerosis, and produces left ventricular hypertrophy.

Eventually, the abnormalities contribute to the Development of

Ischemic Heart Diasease (IHD),
Stroke,
Heart Failure and
Renal Failure.

Regulation of Blood Pressure

Blood pressure is regulated primarily by the Sympathetic Nervous System and the Kidneys via their influence on Cardiac Output
and Peripheral Vascular Resistance (PVR).

Blood Pressure = CO X PVR

Cardiac output = Stroke volume X Heart rate

CO is increased by sympathetic stimulation (via β receptors in the heart) and by kidneys (via their regulation of blood
volume).

PVR is chiefly determined by resistance arterioles (via α -adrenergic receptors)

Baroreceptor Reflex

Short-term regulation of blood pressure is provided by sympathetic nervous system through the baroreceptor reflex.

This reflex modulates sympathetic stimulation of cardiac output and PVR and adjusts B.P. in response to postural changes and
physical activity.

Long-term control of B.P. is maintained by kidneys, via regulation of plasma volume and the Renin-Angiotensin-Aldosterone axis.

In normotensive individuals, an increase in B.P. leads to a proportional increase in sodium and water excretion by the kidneys,
decreasing blood volume and the B.P. returns to its normal ‘set point.’
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In hypertensive patients, the ‘set point’ is set at higher than normal point.
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Sites and Effects of Antihypertensive Drug Action

Various antihypertensive drugs lower blood pressure through actions exerted on one or more of the following sites:
Kidneys,
Sympathetic Nervous System (SNS),
Renin-Angiotensin-Aldosterone axis, or
Vascular Smooth Muscle.

Therefore, there are four major categories of antihypertensive drugs:

-Diuretics
-Sympathoplegics or Sympatholytics
-Inhibitors/blockers of Renin/Angiotensin axis
-Vasodilators

Antihypertensive drugs can also invoke Compensatory Mechanisms by their hypotensive effects.

These compensatory effects tend to return blood pressure to the pretreatment level, and include:

-Reflex tachycardia
-Activation of renin-angiotensin-aldosterone axis
-Fluid retention by the kidneys

Drugs that cause vasodilation tend to invoke compensatory mechanisms to a greater extent than do drugs that suppress cardiac
output, cause diuresis, or inhibit angiotensin.

Vasodilators are often combined with other types of drugs that prevent compensatory responses.

DIURETICS

Thiazide and related Diuretics: Polythiazide, Hydrochlorthiazide, Indapamide, Metolazone

Loop Diuretics: Bumetanide, Furosemide, Torsemide and Ethacrynic acid

Potassium-sparing Diuretics: Amiloride, Spironolactone, Triamterene

Osmotic Diuretics: Glycerol, Mannitol

Carbonic anhydrase Inhibitors: Acetazolamide and Dorzolamide

Thiazides, the Loop diuretics and the Potassium-sparing diuretics are used in the treatment of hypertension.

All diuretics cause an increase in renal sodium excretion.

This so-called natriuretic effect is responsible for much of their antihypertensive activity.

Sodium contributes to vascular resistance by increasing vessel stiffness and neural reactivity, possibly related to increased sodium-
calcium exchange with a resultant increase in intracellular calcium.

Initially diuretics reduce blood pressure by reducing blood volume and cardiac output; PVR may increase during this phase.

After 6-8 weeks, cardiac output returns toward normal, while PVR declines.

Some diuretics have direct vasodilating effects in addition to their diuretic action.

Indapamide is a nonthiazide sulfonamide diuretic with both diuretic and vasodilator activity.

Due to vasodilation, cardiac output remains unchanged or increases slightly

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Diuretics are effective in lowering blood pressure by 10-15 mm Hg in most patients, and often diuretics alone provide adequate
treatment for mild to moderate essential hypertension.

In more severe hypertension, diuretics are used in combination with sympathoplegics and vasodilators to control the tendency
toward sodium retention caused by these agents.

Thiazide diuretics have a moderate natriuretic effect and are appropriate for most patients with mild to moderate hypertension and
normal renal and cardiac function.

Loop diuretics have the greatest natriuretic effect.

They are necessary in severe hypertension, when multiple drugs with sodium retaining properties are used.

In renal insufficiency, when glomerular filtration rate is less than 30 or 40 ml/min, and

In cardiac failure or cirrhosis, where sodium retention is marked.

Potassium-sparing diuretics are useful both to avoid excessive potassium depletion, particularly in patients taking digitalis, and
to enhance the natriuretic effects of other diuretics.

Adverse Effects of Thiazides

Primary disadvantage of Thiazide diuretics is their tendency to cause hypokalemia.

Hypokalemia may predispose patients with heart disease to cardiac arrhythmias.

Using a low dosage minimizes the chances of hypokalemia while producing maximal antihypertensive effect (such as 25-50 mg
of hydrochlorothiazide per day).

Thiazides elevate plasma levels of glucose, uric acid, and lipids in some patients.

Less commonly, they cause hematologic toxicity and aggravate hepatic disease.

Thiazides are also effective against Osteoporosis by decreasing the excretion of Calcium.

Loop and Potassium-sparing Diuretics

Loop diuretics are usually less effective than Thiazides in patients with normal renal function.

Thiazide diuretics lose their effectiveness if renal function declines significantly, whereas loop diuretics continue working.

Loop diuretics are usually reserved for hypertensive patients who have poor renal function and serum creatinine level greater than
2.3 mg/dL.

Unlike Thiazides, Loop diuretics are not beneficial for osteoporosis, because they increase calcium excretion.

Potassium-sparing diuretics have mild natriuretic and antihypertensive effects but reduce renal potassium excretion and thereby
prevent hypokalemia.
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Sympathoplegics or Sympatholytics

Most effective drug regimens for patients with moderate to severe hypertension include an agent that inhibits function of the
SNS.

Drugs in this group are classified according to the site at which they impair the symapethetic reflex arc.
Sympatholytics used for the treatment of hypertension include:

-Adrenergic receptor blockers (antagonists)

-Centrally acting drugs
-Ganglionic blockers
-NE depletors, NE release blockers
-Angiotensin blockers

Drugs that lowers B.P. by action on the CNS tend to cause sedation and mental depression, and may produce disturbances of sleep,
including nightmares.

Drugs that act by inhibiting transmission through autonomic ganglia produce toxicity from inhibition of parasympathetic
regulation, in addition to sympathetic blockade.

Drugs that act chiefly by reducing NE release from sympathetic nerve endings cause effects, including inhibition of ejaculation,
and hypotension, that is increased by upright posture and exercise.

Drugs that block postsynaptic adrenoceptors produce a more selective spectrum of effects depending on the class of receptors to
which they bind.

All agents that lower B.P. by altering sympathetic function can elicit compensatory effects, including Na+ retention and expansion
of blood volume.

Adrenergic Receptor Antagonists

Sympatholytics used most often to treat hypertension are the α -adrenoceptor antagonists (α -blockers) and β -adrenoceptor
antagonists (β -blockers).

β - blockers are the preferred 1st line therapy, whereas α -blockers are 2nd line therapy when other agents are ineffective or
contraindicated.

α -blockers inhibit sympathetic stimulation of arteriolar contraction, and dilate both resistance and capacitance vessels.

α -blockers may cause reflex tachycardia and fluid retention.

Selective α 1-blockers, such as Doxazosin, Prazosin, and Terazosin produce less tachycardia than nonselective α -blockers
(Phentolamine), that block both α 1 and α 2..

Adverse Effects of α -Blockers

α -Blockers cause some activation of SNS and may increase heart rate, contractile force, circulating NE level, and myocardial
oxygen demand.

They do not protect heart against ventricular arrhythmias and are less useful in patients with IHD.

They also activate Renin-Angiotensin-Aldosterone axis, and may cause some fluid retention.

Use of a selective α -blocker with a diuretic causes first-dose syncope in some patients (1st dose phenomenon).

Other side effects include dizziness, palpitations, headache, and lassitude.

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β -Adrenergic Receptor Blockers

β -blockers are widely used because they are relatively safe and effective in most patients who suffer from angina or have a
history of myocardial infarction.

β -blockers are cardioprotective and rarely cause orthostatic hypotension or produce hepatic, renal or hematopoietic toxicity.

They can be used as single-drug therapy for mild hypertension or combined with other drugs to treat more severe forms of
hypertension.

β 1-blockade in heart and other tissues reduces cardiac output by decreasing heart rate and contractility.

β -blockers inhibit renin secretion, that reduces the ultimate formation of angiotensin II and the subsequent release of aldosterone.

β -blockers also reduce sympathetic outflow from the CNS; thus, they have multiple actions affecting B.P.

Propranolol was the 1st β -blocker shown to be effective in hypertension and IHD.

All β -blockers have now been proven effective for mild to moderate hypertension.

In cases of severe hypertension, β -blockers are used in conjunction with other antihypertensives.

β -blockers have been shown to reduce mortality in patients with heart failure, and are particularly advantageous in this group.

Propranolol decreases B.P. primarily by decreasing cardiac output.

Other β -blockers may decrease cardiac output or decrease PVR to various degrees, depending on cardioselectivity and partial
agonist activities.

Withdrawal syndrome, manifested by nervousness, tachycardia, increased intensity of angina, or increase of blood pressure may
occur in some patients at discontinuation after prolonged use.

Other nonselective β -blockers are Nadolol and Carteolol.

Selective β 1-blockers, such as Atenolol, Metoprolol, Betaxolol and Bisoprolol, are preferred for hypertensive patients with
diabetes, obstructive pulmonary disease or peripheral vascular disease.

Metoprolol is not absolutely cardioselective.

Atenolol is less lipophilic than propranolol and usually causes fewer CNS side effects.

Betaxolol and Bisoprolol are primarily metabolized in the liver and have long half-lives; thus, can be administered once daily.

Pindolol, Acebutolol and Penbutolol are partial agonists, i.e. β -blockers with intrinsic sympathomimetic activity (ISA).

They lower B.P. by decreasing PVR and decrease cardiac output or heart rate less than other β -blockers.

They may be useful for patients with bradyarrhythmias or peripheral vascular disease.

Labetalol, a combined α - and β -blocker is used to treat both chronic hypertension and hypertensive emergencies.

Most patients with IHD, including those with angina pectoris or MI should be treated with a β -blocker* unless it is
contraindicated.
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Centrally-Acting Antihypertensives

These agents reduce sympathetic outflow from vasopressor centers in the brainstem to the heart, blood vessels, and other tissues,
but allow them to retain or even increase their sensitivity to baroreceptor control.

These agents are α 2-adrenergic receptor agonists. They reduce blood pressure by reducing PVR while the heart rate and cardiac
output are either reduced or remain unchanged.

The antihypertensive and toxic effects of these agents are generally less dependent on posture than the effects of drugs directly
influencing peripheral sympathetic neurons.

Since TCAs can block the effects of centrally-acting sympatholytics, the two classes of drugs should not be used concurrently.

Centrally-acting sympatholytics used for the treatment of hypertension include:

Clonidine
Guanabenz
Guanfacine, and
Methyldopa

Sedation, dry mouth, and other CNS side effects of these drugs may be problematic in patients whose work requires mental
alertness, also in elderly and those with neurologic diseases.

The sedative effects subside after a few weeks of treatment.

Severe rebound hypertension may occur if the drug is discontinued abruptly, the dosage should be tapered gradually over 1-2
weeks period.

Clonidine

Clonidine lowers B.P. by reducing cardiac output due to decreased heart rate and relaxation of capacitance vessels, with a
reduction in PVR, particularly when the patients are upright.

The drug is also classified as partial agonist at α -receptors because it also inhibits pressor effects of other α -agonists.

Dry mouth and sedation are frequent adverse effects and may be severe.

The drug should not be given to patients who are at risk for mental depression and should be withdrawn if depression occurs
during therapy. (CI: TCAs)

Withdrawal of Clonidine after protracted use in high doses can result in life-threatening hypertensive crisis.

Methyldopa

Methyldopa is an analogue of L-dopa and is similar to Clonidine in its actions and effects.

Unlike Clonidine and other centrally-acting drugs, Methyldopa is accumulated by central noradrenergic neurons and is converted
to α -methylnorepinephrine is stored in adrenergic nerve vesicles, where it replaces NE, and is released by nerve stimulation.

Antihypertensive action of Methyldopa is due to stimulation of central α -adrenoceptors by α -methylnorepinephrine or α -

methyldopamine.

Methyldopa lowers B.P. chiefly by reducing PVR with a variable reduction in heart rate and cardiac output.

Methyldopa is often preferred for the treatment of hypertension in pregnant women, since its use does not harm the fetus.
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Adverse Effects: Postural hypotension sometimes occurs; it causes reduction in renal vascular resistance (advantage).

Most frequent adverse effect is sedation; with long-term therapy, lassitude and impaired mental concentration.

Nightmares, mental depression, vertigo and extrapyramidal signs may occur but are relatively infrequent.

Lactation can occur both in men and women due to increased prolactin secretion.

Other important adverse effects include positive Coomb’s test (10-20% of patients w/ more than 12 months of therapy), hemolytic
anemia, hepatitis and drug fever.

Ganglion-blocking Agents

Drugs that block stimulation of postganglionic autonomic neurons by acetylcholine were among the 1st agents used in the treatment
of hypertension.

The only agent currently used is Trimethaphan.

Ganglion blockers competitively block nicotinic cholinoceptors on postganglionic neurons in both sympathetic and
parasympathetic ganglia.

These drugs may directly block the nicotinic ACh channels on neuromuscular junction.

Adverse effects include both sympathoplegia (excessive orthostatic hypotension, sexual dysfunction) and parasympathoplegia
(constipation, urinary retention, blurred vision, dry mouth, glaucoma, etc.)

Neuron Blocking Agents

These drugs lower B.P. by preventing normal physiologic

release of NE from postganglionic sympathetic
neurons.

Guanethidine and Reserpine are the major drugs in this

class.

Guanethidine inhibits the release of Norepinephrine from

sympathetic nerve endings, and is responsible for the
sympathoplegic effect.

It is transported across the sympathetic nerve membrane

that transports NE itself; and uptake is essential for the
drug’s effect.

After entering the nerve terminal, it is concentrated in

transmitter vesicles, and replaces NE, causing a gradual depletion of NE stores in the nerve ending.

Cocaine, TCAs, Phenothiazines and Phenoxybenzamine block its effects.

Reserpine

Reserpine is an alkaloid of Rauwolfia serpentina, and was one of the 1st effective drugs used on a large scale for the treatment of
hypertension.
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It is still considered an effective and relatively safe drug for the treatment of mild to moderate hypertension.

Reserpine blocks the ability of aminergic transmitter vesicles to take up and store neurotransmitters.

This effect occurs throughout the body, resulting in depletion of Norepinephrine, Dopamine and 5-HT in both central and
peripheral neurons.

Chromaffin granules of the adrenal medulla are also depleted of catecholamines to a lesser extent.

Depletion of peripheral amines probably accounts for much of the beneficial antihypertensive effects.

Reserpine readily enters the brain, and depletion of cerebral amines causes sedation, mental depression, and Parkinsonism
symptoms.

Reserpine produces little postural hypotension.

Reserpine produces mild diarrhea and gastrointestinal cramps, and increases gastric acid secretion.

It should not be used in patients with a history of peptic ulcer.

ANGIOTENSIN INHIBITORS

Angiotensin inhibitors include the Angiotensin-Converting

Enzyme (ACE) Inhibitors and the Angiotensin Receptor
Blockers or Antagonists (Arb).

β -blockers also reduce angiotensin by inhibiting sympathetic

stimulation of renin secretion by kidneys.

Causative roles of renin, angiotensin, and aldosterone in

essential hypertension remain controversial.

Approximately 20% of patients with essential hypertension

have abnormally low and 20% have abnormally high
plasma renin activity.

Blood pressure of patients with high-renin hypertension

responds well to both β -blockers and angiotensin
inhibitors.

Angiotensin-Converting Enzyme (ACE) Inhibitors

Various ACE inhibitors have identical mechanisms of action and pharmacological effects, and differ only in their pharmacokinetic
properties.

ACE inhibitors include:

Benazepril Captopril Enalapril Fosinopril Lisinopril,
Moexipril Perindopril Quinapril Ramipril Trandolapril

All ACE inhibitors inhibit the converting enzyme peptidyl dipeptidase (Angiotensin Converting Enzyme) that hydrolyzes
angiotensin I to angiotensin II, and inactivates bradykinin.

Bradykinin is a potent vasodilator.

ACE inhibitors lower blood pressure by decreasing PVR.

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Cardiac output and heart rate are not significantly changed.

Unlike direct vasodilators, these agents do not cause reflex sympathetic activation and can be used safely in patients with Ischemic
Heart Disease.

By reducing angiotensin-stimulated aldosterone secretion, ACE inhibitors prevent the compensatory increase in sodium retention
and plasma volume.

In patients treated with ACE inhibitors, renal Na+ retention is decreased, and renal K+ retention is increased

Although ACE inhibitors are most effective in patients with high plasma renin activity, there is no good correlation among subjects
between plasma renin activity and antihypertensive response.

ACE inhibitors have a particularly useful role in patients with diabetic retinopathy because they diminish proteinuria and stabilize
renal function.

ACE inhibitors are also extremely useful in the treatment of heart failure, and after MI.

Adverse Effects

Acute renal failure

Hyperkalemia
Dry, irritating, nonproductive cough (sometimes accompanied by wheezing), and
Angioedema

Hyperkalemia is more likely to occur in patients with renal insufficiency or diabetes.

Bradykinin and substance P seem to be responsible for cough and angioedema.

Bradykinin and substance P may also cause an abnormal taste sensation.

Contraindications

ACE inhibitors are contraindicated in:

Bilateral renal artery stenosis,
Hypersensitivity, and
Pregnancy

Drug Interactions

ACE inhibitors:
-increase serum levels of lithium.
-hyperkalemic effect is increased by K+-sparing diuretics and potassium supplements.
-hypotensive effect is decreased by NSAIDs.

Captopril reduces blood pressure by both an inhibitory action on renin-angiotensin system and a stimulating action on kallikrein-
kinin system.

Enalapril is a prodrug that is converted to Enalaprilate.

Enalaprilate itself is marketed for intravenous use in hypertensive emergencies.

Lisinopril is a lysine derivative of Enalaprilate.

Benazepril, Fosinopril, Moexipril, Perindopril, Quinapril, Ramipril and Trandolapril are long-acting members of the class.
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They are all prodrugs, like Enalapril, and are converted to active metabolites by hydrolysis, primarily in the liver.

Angiotensin Receptor Antagonists (ARBs)

Angiotensin receptor antagonists block AT1 receptors in vascular smooth muscle and in the adrenal cortex, thereby causing
vasodilation and decreasing aldosterone secretion.

ARBs are as effective as ACE inhibitors but only rarely cause chronic cough and are relatively free of other adverse effects.

ARBs do not increase serum glucose, uric acid or cholesterol levels

They may cause occasional abnormalities in test results for hepatic aminotransferase enzymes.

Like ACE inhibitors, ARBs may cause fetal injury and death, and should not be used during pregnancy.

Candesartan (AtacandR), Losartan (CozaarR), Omisartan (BenicarR), Telmisartan (MicardisR) and Valsartan (DiovanR).

VASODILATORS

Vasodilators include the Calcium Channel Blockers and other agents such as Hydralazine, Minoxidil, and Nitroprusside.

Oral Vasodilators, Hydralazine and Minoxidil, are used for long-term outpatient therapy for hypertension.

Parenteral vasodilators, such as Nitroprusside, Diazoxide and Fenoldopam are used to treat hypertensive emergencies.

Calcium channel blockers are used in both circumstances.

All vasodilators useful in hypertension relax smooth muscle of arterioles, decreasing systemic vascular resistance.

Decreased arterial resistance and mean arterial B.P. elicit compensatory responses, mediated by baroreceptors and SNS, as well as
renin, angiotensin and aldosterone.

Hydralazine

Hydralazine dilates arterioles but not veins. It is well absorbed and rapidly metabolized by the liver during the 1st pass;
bioavailability about 25%.

It requires dosing 2-3 X daily and provides smooth control of blood pressure.

Most common adverse effects include headache, nausea, anorexia, palpitations, sweating, and flushing.

In patients with Ischemic heart disease, reflex tachycardia and SNS stimulation may provoke angina or ischemic arrhythmias.

In higher doses (400 mg/d or more), chiefly in slow acetylators, hydralazine produce a (reversible) lupus erythematosus-like
syndrome, characterized by arthralgia, myalgia, skin rashes and fever (10-20%). The syndrome is not associated with renal
damage.

Minoxidil

Minoxidil is a very efficacious orally active vasodilator. The effect results from opening of K+ channels in smooth muscle
membranes by Minoxidil sulfate, the active metabolite.

This action stabilizes the membrane at its resting potential and makes contraction less likely.

Like Hydralazine, Minoxidil dilates arterioles but not veins but has higher antihypertensive potential.
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Minoxidil is associated with even more reflex SNS stimulation and sodium and fluid retention.
Minoxidil must be used in combination with a β -blocker and a loop diuretic.

Adverse Effects: Tachycardia, palpitations, angina, and edema. Headache, sweating and Hirsutism are relatively common, and
bothersome in women.

Sodium Nitroprusside

Sodium nitroprusside is a powerful parenterally administered vasodilator, used in treating hypertensive emergencies as well as
severe heart failure.

Nitroprusside is a complex of iron, cyanide groups and a nitroso moiety, is rapidly metabolized by uptake into RBCs with
liberation of cyanide.

Cyanide is metabolized by the mitochondrial enzyme to the less toxic thiocyanate.

Nitroprusside rapidly lowers blood pressure after intravenous injection and its effect disappears within 1-10 minutes after
discontinuation.

Sodium nitroprusside in aqueous solution is sensitive to light and must be made up fresh before each administration and covered
with opaque foil.

Infusion solutions should be changed after several hrs.

It dilates both arterial and venous vessels, resulting in reduced PVR and venous return.

This action is the result of activation of guanylyl cyclase, either via a release of Nitric Oxide (NO) or by direct stimulation of the
enzyme.

The increased intracellular cGMP relaxes vascular smooth muscle.

In the absence of heart failure, B.P. decreases due to decreased PVR, while cardiac output does not change or decreases slightly.

In patients with heart failure and low cardiac output, output often increases due to afterload reduction.

Adverse effects:

Most serious toxicity is due to accumulation of cyanide; metabolic acidosis, arrhythmias, excessive hypotension, and death.

Administration of sodium thiosulfate, as a sulfate donor, facilitates metabolism of cyanide.

Thiocyanate may accumulate over the course of prolonged administration (usually a week or more), particularly in patients with
renal insufficiency.
Thiocyanate toxicity is manifested as weakness, disorientation, psychosis, muscle spasms and convulsions.

Diazoxide

Diazoxide is chemically similar to thiazide diuretics with no diuretic activity.

It is an effective and relatively long-acting parenterally administered arteriolar dilator, occasionally used to treat hypertensive
emergencies.

Intravenous injection results in rapid fall in systemic vascular resistance and mean arterial B.P., associated with substantial
tachycardia and increase in cardiac output.

It prevents vascular smooth muscle contraction by opening K+ channels and stabilizing the membrane potential at the resting level.
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Adverse effects: Excessive hypotension results in stroke and MI. Reflex SNS response can provoke angina, ischemia and
cardiac failure in patients with IHD.

Diazoxide inhibits insulin release from pancreas and is used to treat hypoglycemia secondary to insulinoma.
Calcium Channel Blockers (CCBs)

Calcium channel blockers are used in the treatment of hypertension, angina pectoris, and cardiac arrhythmias.

They relax vascular smooth muscle by inhibiting calcium influx into plasma membranes of smooth muscle cells.

They have a greater effect on arteriolar smooth muscle than on venous smooth muscle.

Antihypertensive effect is primarily due to reduction in PVR, with relatively little impact on venous capacitance, cardiac filling
pressure, and cardiac output.

CCBs are effective in all forms of hypertension and are the most widely used.

CCBs do not alter serum glucose, lipids, uric acid, or electrolytes levels.

They are relatively free of adverse effects and are particularly useful in treating hypertension in patients with asthma or of African
heritage.

Verapamil, Diltiazem and the dihydropyridine class (Amlodipine, Felodipine, Isradipine, Nicardipine, Nifedipine, and Nisoldipine)
are all equally effective in lowering B.P. and only hemodynamic differences influence the choice of a particular agent.

Diltiazem and Verapamil also have a significant (depressant) effect on cardiac tissue and reduce the heart rate in some patients.

Nifedipine and other dihydropyridines have relatively little effect on cardiac tissue.

They may evoke reflex tachycardia, and some are reported to suppress cardiac contractility in patients with heart failure.

Malignant Hypertension

Malignant hypertension is an advanced phase of severe hypertension with rising blood pressure and rapidly progressing damage to
end organs.

This condition is characterized by deterioration of renal function, encephalopathy and retinal hemorrhage, or by angina, stroke, or
myocardial infarction.

Malignant hypertension is a medical emergency and must be dealt with quickly.

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Powerful vasodilators (Nitroprusside or Diazoxide) are combined with diuretics and β -blockers to lower blood pressure to 140-
160/90-110 range within a few hours.

Management (Treatment) of Hypertension

Treatment of hypertension requires long-term drug therapy. Selection of a drug is primarily based on their adverse effect profile,
contraindications, cost and convenience to the patient.

The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends that
physicians begin with a single-drug therapy, since monotherapy reduces cost, adverse effects, and noncompliance by patients.

The committee recommends that a β -blocker or a diuretic be used initially for most hypertensive patients.

An ACE inhibitor, a CCB, or an α 1-blocker can be used as an alternative when β -blockers or diuretics are unsuitable.

A 2nd drug is added or substituted for the 1st drug if it does not provide adequate control.

In some cases, 3 drugs may be required to effectively control B.P.

Unless intolerable side effects occur or hypertension is severe, drugs should be given a trial of several weeks before evaluating
their effectiveness or changing the medication.

Patients over 65 years old: Use of a thiazide diuretic, an ACE inhibitor, or a dihydropyridine CCB is often preferred for initial
therapy in patients over 65 yrs old.

In elderly black patients, β -blockers are often less effective than diuretics, so a diuretic and a CCB should be used.

Patients with Concomitant Diseases: Patients with hypertension and a coexisting disorder should be treated with drugs that are
potentially beneficial to both conditions.

Most patients with IHD, including those with angina and MI, should be treated with a β -blocker unless contraindicated.

Diuretics may cause hypokalemia, which predisposes to ventricular arrhythmia, and are less useful in patients with IHD or
ventricular hypertrophy.

α -blockers, ACE inhibitors, CCBs, or Indapamide is preferred in patients with hypercholesterolemia, because these agents do not
adversely affect lipid profile.

In diabetic patients, treatment with an ACEI, α -blocker, or CCB is often preferred because they do not prolong hypoglycemia like
β -blockers. Diuretics are not preferred as they increase blood glucose level in many cases.
β -blockers should be avoided in patients with asthma. Use of a CCB or ACE inhibitor is usually preferred.