Drugs used in Hypertension

BY: Dr. Tanvi H. Desai

(M.Pharm, Ph.D)
 Introduction
• Hypertension (rise in BP) is one of the common cardiovascular disorders of modern
times According to WHO, hypertension is the state of the body in which systolic BP
is 150 mmHg or more and diastolic BP is 95 mmHg or more.
• If one applies strictly WHO definition one third of men and two-fifth of women over
40 years of age are hypertensive because as age advances, there is pari-passu
increase in BP.
• In general, an individual with diastolic pressure above 100 mmHg is considered to
be hypertensive and needs treatment.
• Systolic BP is often fluctuating, but may be persistent very high systolic BP is also
fraught with danger.
• Hypertension may be classified into Primary and Secondary.
• Primary or essential hypertension is characterized by elevation of diastolic BP, a
normal cardiac output (in most of the cases) and an increase in peripheral
resistance with a documented etiology.
• The etiology of primary hypertension is not clear but several factors are implicated in its genesis. They are:

• (a) Genetic (family history of vascular disease)

• (b) Obesity and glucose intolerance
• (c) High salt intake.
• (d) Cigarette smoking.
• (e) Hyperlipidaemia.
• (f) Increased serum renin levels.
• (g) Hypersensitivity of sympathetic system.

• About 80 to 90% cases of hypertension belong to primary type of hypertension.

• Secondary hypertension is the type where etiology is known. It is Secondary' to some disorder.

• Common disorders causing hypertension are as follows:

• 1. Acute or chronic renal disease (particularly glomerulonephritis).

• 2. Renal artery stenosis (atheroma in older age group and fibromuscular hyperplasia in younger age
group).
• 3. Hyperaldosteronism
• 4. Cushing's syndrome.
 • 5. Acromegali.
• 6. Pheochromocytoma
• 7. Drugs like oral contraceptives, estrogens, steroids carbenoxolone and
sympathomimetics.
• Hypertension is one of the major risk factors of various diseases like myocardial ischaemia,
cardiac failure, renal failure, and stroke.
• The efficacy of antihypertensive treatment depends nod only on the control of the B.P., but
on the co-existence of other risk factors.
• Control of blood pressure is very essential to reduce the mortality among such patients.
• There are number of drugs available to control blood pressure, however, non-
pharmacological therapy must be started in all hypertensives. These include the following:

• (a) Weight reduction.

• (b) Increased aerobic exercise.
• (c) Salt restriction (5-6 gm NaCl).
• (d) Relaxation and stress management
• (e) Supplementation of potassium, calcium and magnesium.
• (f) Use of fish oil.
• (g) Cessation of smoking and alcohol.
 Classification of Antihypertensive agents
• 1. Diuretics:
• A. Thiazides: Hydrochlorothiazide, Chlorthalidone, Indapamide

• B. High ceiling: Furosemide, etc.

• C. K+ Sparing: Spironolactone, Amiloride

• 2. ACE inhibitors: Captopril, Enalapril, Lisinopril, Perindopril, Ramipril, Fosinopril, etc.

• 3. Angiotensin (AT1 receptor) blockers: Losartan, Candesartan, Irbesartan, Valsartan,

Telmisartan

• 4. Calcium channel blockers: Verapamil, Diltiazem, Nifedipine, Felodipine, Amlodipine,

Nitrendipine, Lacidipine, etc.

• 5. β Adrenergic blockers: Propranolol, Metoprolol, Atenolol, etc.

• 6. β + α Adrenergic blockers: Labetalol, Carvedilol

• 7. α Adrenergic blockers: Prazosin, Terazosin, Doxazosin Phentolamine,

Phenoxybenzamine

• 8. Central sympatholytic: Clonidine, Methyldopa

• 9. Vasodilators:
• a. Arteriolar: Hydralazine, Minoxidil, Diazoxide

• b. Arteriolar + venous: Sodium nitroprusside Adrenergic neurone blockers

(Reserpine, Guanethidine, etc.) and ganglion blockers (Pentolinium, etc.) are only of
historical importance, though reserpine is still marketed.
•Diuretics
• Diuretics may be considered as the first line of drugs for the treatment of mild
hypertension.
• MOA: These agents increase the urine volume and thereby decrease cation concentration in
blood, extracellular fluid volume, plasma volume, followed by decrease in peripheral
resistance and normalization of cardiac output.
• These actions produce decrease in peripheral resistance and lower the blood pressure.
• Thiazides and related drugs (chlorthalidone, etc.) are the diuretic of choice in
uncomplicated hypertension. The proposed mechanism of antihypertensive action is:
• 1. Initially, the diuresis reduces plasma and e.c.f. volume by 5–15% → decreased c.o.

• 2. Later, compensatory mechanisms operate to almost regain Na+ balance and plasma volume; c.o. is
restored, but the fall in BP is maintained by a slowly developing reduction in total peripheral resistance
(TPR)

• Decrease in intracellular Na+ concentration in the vascular smooth muscle may decrease stiffness of
vessel wall, increase their compliance and reduce responsiveness to constrictor stimuli (NA, AII).
 • Similar effects are produced by salt restriction; and antihypertensive action of diuretics is lost when salt
intake is high.
• A mild slowly developing vasodilator action of thiazides due to opening of smooth muscle K+ ATP
channels and hyperpolarization has been proposed.

• Thiazides are weak diuretics but useful antihypertensives.

• They are well absorbed orally, widely distributed and metabolized in the liver. Renal actions depend on
the excretion of the drug into the tubule.

• Thus, thiazides may be ineffective, if there is renal impairment.

• The onset of action may be observed within 60 minutes and may last for 12 hours or more.
Hydrochlorhiazide and chlorthialidone are generally preferred as antihypertensive diuretics.
• High ceiling diuretics (Loop diuretics) Furosemide, the prototype of this class, is a strong diuretic, but
the antihypertensive efficacy is less.
• Furosemide is a weaker antihypertensive than thiazides: fall in BP is entirely dependent on reduction in
plasma volume and c.o.

• The natriuretic action lasting only 4–6 hr after the conventional morning dose is followed by
compensatory increase in proximal tubular reabsorption of Na+.
• Moreover, the high ceiling diuretics are more liable to cause fluid and electrolyte imbalance,
weakness and other side effects.
• In hypertensive patients loop diuretics are indicated only
• (a) in chronic renal failure when thiazides are inactive.
• (b) in hypertension resistant to standard triple therapy including a thiazide,
• (c) in combination with vasodilators or angiotensin converting enzyme inhibitors in severe
resistant hypertension and
• (d) in coexisting refractory congestive cardiac failure.
• Potassium sparing diuretics Spironolactone or amiloride themselves lower BP slightly, but they are
used only in conjunction with a thiazide diuretic to prevent K+ loss and to augment the
antihypertensive action.
• They should not be used with ACE inhibitors as they may produce hyperkalemia.

• Potassium sparing diuretics are contraindicated if patient is taking any potassium supplements.
• Adverse effects of diuretics include hypokalemia, hyperuraemia, hyperglycemia, hypercalcemia,
impotence, skin rashes and thrombocytopenia, atherogenic (tending to promote the formation of
fatty deposits in the arteries). Renal functions must be monitored during diuretics therapy.
• ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORS:

• ACE inhibitors block specifically the enzyme ACE and thereby decrease the Angiotensin II which is responsible for
vasoconstriction and aldosterone secretion.

• Hence, ACE inhibitors cause vasodilatation, decreased sodium and water retention leading to decrease in blood pressure.

• A number of ACE inhibitors have been discovered. Captopril, the oldest one is having sulfhydryl group. Enalapril, Lisinopril,
Ramipril, Fosinopril and Perindopril are also available in India.

• Many are under investigation. They are Benazepril, Indolapril, Pivalopril, Zofenopril, Spirapril, Alacepril, Rentiapril, Delapril
and Trandolapril.

• Renin-angiotensin system is found not only in kidney but also in blood vessels, heart, brain, testes, lungs and medulla
oblongata.

• Pharmacological Actions: Antihypertensive effects:

• ACE inhibitors are likely to have a beneficial effect in hypertension with associated cardiac problems.

• It is now well known that ACE inhibitors are effective in reducing blood pressure even when renin levels are not elevated.

• These agents do not induce tachycardia. They are extremely useful in treating essential hypertension in the elderly and also
patients with heart failure.

• As compared to many antihypertensives ACE inhibitors are lipid neutral and do not produce significant metabolic side
effects and thus may be considered better than other agents.
• Pharmacokinetics: ACE inhibitors are in general absorbed orally.
• The peak effect is reached for captopril and enalapril within an hour. However, for lisinopril
it may take about 7 hours.
• Enalapril cilazapril and ramipril are prodrugs and are converted into active metabolites
enalaprilat, cilazaprilat and ramiprilat respectively.
• Except for lisinopril most ACE inhibitors are metabolized in liver. Captopril and enalapril are
excreted from kidney by glomerular filtration and tubular secretion. Lisinopril is excreted by
glomerular filtration only.
• Captopril and cilazapril have shorter plasma half life (1.0 - 2.0 hours) whereas, lisinopril,
enalapril and ramipril have longer plasma half life (10-13 hours).
• Therapeutic Uses:
• 1. Hypertension
• 2.Congestive heart failure.
• 3.Myocardial infarction when there is ventricular dysfunction
• 4. Diabetic nephropathy
• 5. Progressive renal insufficiency
• Adverse Effects: Cough, hypotension, renal failure, angioedema and hyperkalaemia are the
common side effects
• ANGIOTENSIN RECEPTOR ANTAGONISTS:
• Losartan: It is an Angiotensin-II, AT, receptor antagonist.

• Angiotensin-II, a peptide is formed from Angiotensin-I by the enzyme Angiotensin

Converting Enzyme (ACE).
• Angiotensin-II produces cardiovascular action by acting on AT receptor.
• It increases total peripheral vascular resistance by direct vasoconstriction, enhancing
peripheral noradrenergic neurotransmission and enhancing central sympathetic.
• It also stimulates release of aldosterone from adrenal cortex and vasopressin from
posterior pituitary gland.
• All these effects result in increased blood pressure.
• Angiotensin II also produces cardiac hypertrophy.
• Hence it is an important target in the treatment of cardiovascular disorder.
• Mechanism of Action: AT, receptor is a G protein coupled receptor. It increase release of calcium
via Gq-DAG-IP3 pathway thereby causes vascular smooth muscle contraction.
• By blocking AT, receptor, these agents cause vascular smooth muscle relaxation, increase in renal
salt and water excretion, reduction in plasma volume and decrease in cardiac hypertrophy.

• Absorption and Excretion: Losartan is an orally active agent that undergoes substantial first-pass
metabolism by cytochrome P450 enzymes.

• It is converted, in part, to an active a carboxylic acid metabolite that is responsible for most of the
angiotensin II receptor antagonism that follows losartan treatment.

• The terminal half-life of losartan is about 2 hours and of the metabolite is about 6-9 hours.

• Adverse effects: Hypotension is most likely to occur in patients in whom the blood pressure is
highly depended on angiotensin II including those with volume depletion (e.g. with diuretics).

• Hyperkalemia may occur in conjunction with other factors that alter K+ homeostasis, such as renal
insufficiency, ingestion of excess K+, and the use of drugs that promote K+ retention.
• CALCIUM CHANNEL BLOCKERS:
• The contractile process of cardiac and vascular smooth muscles depend upon the movement of
extracellular calcium ions in these cells through specification channels (slow calcium channels)
• Voltage-sensitive Ca2+ channels (L-type or slow channels) mediate the entry of extracellular Ca2+
into smooth muscle and cardiac myocytes and sinoatrial (SA) and atrioventricular (AV) nodal cells in
response to electrical depolarization.
• In both smooth muscle and cardiac myocytes, Ca2+ is a trigger for contraction, but by different
mechanisms. Ca2+ channel antagonists, also called Ca2+ entry blockers inhibit Ca2+ channel
function.
• In vascular smooth muscle, this leads to relaxation, especially in arterial beds.
• These drugs also may produce negative inotropic and chronotropic effects in the heart.
• They also cause relaxation of vascular smooth muscles and thereby decrease in blood pressure.
• The first useful calcium channel blocker discovered was verapamil the derivative of papaverine.
Later, nifedipine (dihydropyridine) and diltiazem (benzothiazine) were discovered. These three are
widely used and are called the first generation calcium channel blockers.
• Second generation calcium channel blockers are mostly dihydropyridines (like nifedipine) and
amlodipine having minimum negative inotropic effect.
• Amlodipine possesses longer half life and has a better pharmacokinetic profile than nifedipine.
• Other second generation calcium channel blockers are felodipine, nicardipine, nimodipine and
nisoldipine.

• Recently, third generation calcium channel blockers have been introduced. Examples are Monatepil,
Lacidipine.

• Pharmacokinetics and Dosage: Verapamil is given orally in the dose of 40 mg 8 hourly or by

infusion in the dose if 0.1 to 0.15mg over a period of 2 min.
• The onset of action is 30 min (oral) or 1-2 min (iv). The peak effect is reached in 5 hours (oral) or 10-
15 min (iv). 90% of the drug is bound to plasma proteins. 70% of the drug is eliminated within 7-10
hours as the metabolites through urine.
• Nifedipine can be given sublingually and has greater bioavailability (65-70%) as compared to
verapamil (10-22%). It can be given, even if there is renal failure. Dose is 10 mg 8 hourly.
• The onset of action is 3-7 min, peak effect is reached in 1-2 hours. 90% of the drug is bound to
plasma proteins. It is metabolized in liver and excreted through urine. Common adverse effects of
calcium antagonists are headache, flushing and edema of the ankle joint.
• Adverse effects: Various adverse effects of calcium channel blockers include flushing, headache,
swelling in ankle. Verapamil is known to cause constipation and decrease in heart rate.
• β-ADRENERGIC BLOCKERS
• They are mild antihypertensives; do not significantly lower BP in normotensives. Used alone in 30–40% patients—
mostly mild to moderate cases.

• In the large majority of the rest, they can be usefully combined with other drugs.

• The hypotensive response to β blockers develops over 1–3 weeks and is well sustained. Despite short and differing
plasma half lives, the antihypertensive action of most β blockers is maintained over 24 hr with a single daily dose.

• There are several contraindications to β blockers, including cardiac, pulmonary and peripheral vascular disease.

• The nonselective β blockers have an unfavorable effect on lipid profile (raise triglyceride level and LDL/HDL ratio).

• They have also managed poorly on quality of life parameters like decreased work capacity, fatigue, loss of libido and
subtle cognitive effects (forgetfulness, low drive), nightmares and increased incidence of antidepressant use.

• However, most of these drawbacks are minimized in the β1 selective agents and in those which penetrate brain
poorly.

• Thus, there are several reasons to prefer a β1 selective hydrophilic drug like atenolol over propranolol.

• Because of absence of postural hypotension, bowel alteration, salt and water retention; a low incidence of side
effects, low cost; once a day regimen and cardioprotective potential, β blockers continue to be among the first
choice drugs
• α+β ADRENERGIC BLOCKERS
• Labetalol: It is a combined α and β blocker; reduces t.p.r. and acts faster than pure β blockers. It has been
used i.v. for rapid BP reduction in cheese reaction, clonidine withdrawal, etc.
• Oral labetalol therapy is restricted to moderately severe hypertension not responding to pure β blocker. Side
effects of both α blocker and β blocker occur with it.
• Carvedilol: This nonselective β + selective α1 blocker produces vasodilatation and has additional
antioxidant/ free radical scavenging properties.
• It has also been used in CHF. Side effects are similar to labetalol; liver enzymes may rise in some.

• α-ADRENERGIC BLOCKERS
• Prazosin
• This prototype selective α1 antagonist dilates both resistance and capacitance vessels.
• The haemodynamic effects—reduction in t.p.r. and mean BP with only slight decrease in venous return and
c.o. are similar to that produced by a direct acting vasodilator.
• Cardiovascular reflexes are not appreciably impaired by chronic therapy, but postural hypotension and
fainting may occur in the beginning—called ‘first dose effect’, and with dose increments.
• This disappears with continued therapy, but may persist in the elderly.
• For this reason, prazosin is always started at low dose (0.5 mg) given at bedtime and gradually
increased with twice daily administration till an adequate response is produced (max. dose 10 mg
BD).

• Patients who develop marked first dose effect generally require lower maintenance doses (2–6 mg/
day).

• An oral dose produces peak fall in BP after 4–5 hours and the effect lasts for nearly 12 hours,
though plasma t½ is only 3 hours. This may be due to generation of active metabolites.
• Adverse effects: Prazosin is generally well tolerated at low doses. Apart from postural hypotension
related symptoms (to which tolerance frequently develops), other side effects are headache,
drowsiness, dry mouth, weakness, tremor, nasal blockade, blurred vision and rash.
• Ejaculation may be impaired in males: especially with higher doses. Fluid retention tendency of
prazosin monotherapy may precipitate CHF.

• It may be added to a diuretic + β blocker in those not achieving target BP.

• Terazosin, Doxazosin: These are long-acting congeners of prazosin with similar properties and
suitable for once daily dosing.
• CENTRALLY ACTING SYMPATHETIC DRUGS
• CLONIDIN: It is an imidazole derivative, commonly used as antihypertensive agent.
• Mechanism of Action : Clonidine stimulates specifically α2-adrenoceptors.

• Stimulation of these receptors in CNS produce fall in blood pressure. The α2-adrenoceptors in periphery are situated on
presynaptic membrane and regulate the release of noradrenaline.
• <<

• Stimulation of these presynaptic α2 receptors, inhibits release of noradrenaline. The other mechanism is decrease in plasma
renin levels.

• Pharmacological Actions : Clonidine, when given intravenously, produces short time hypertension followed prolonged
decrease in systolic and diastolic blood pressure. When given orally, it produces decrease in blood pressure. Addition of
diuretics enhances antihypertensive action.
• Clonidine does affect baroreceptor reflexes and hence, does not produce postural hypotension. Howe clonidine produces
bradycardia and so it is not good for emergency use. It also decrease cardiac output.
• Clonidine produces sodium retention and tolerance develops to antihypertensive action after prolonged use. Hence,
diuretics are given along with clonidine.
• Pharmacokinetics : Clonidine is absorbed well from g.i. tract and has high volume of distribution. Its plasma- half life is 12
hours. It is excerted unchanged in urine. Therapeutically, it is used in hypertension in the dose of 100 µg given twice daily.
• Adverse effects: Drowsiness, dryness of mouth, constipation, vertigo and impotence are commonly observed adverse
effects. Abrupt cessation of clonidine can produce rebound hypertension hence it should be withdrawn slowly.
• Interactions: Tricyclic antidepressants and chlorpromazine abolish the antihypertensive action of clonidine, probably by
blocking α receptors on which clonidine acts.

• Alphamethyldopa:
• It is a drug of choice for eclampsia (seizure) in pregnancy. It is the isomer of methyldopa which bears a close similarity with
dihydroxyphenylalanine (DOPA).

• It is converted into a-methylnoradrenaline which acts as the false transmitter. In other words, it prevents actions of
noradrenaline.

• It has been proposed that a-methylnoradrenaline also activates central α2-receptors to produce fall in blood pressure. Alpha
methyldopa inhibits DOPA decarboxylase and thereby decreases noradrenaline synthesis. Another mechanism proposed for
the antihypertensive action of a-methyldopa is inhibition of renin release.

• Pharmacological Actions :

• Alphamethyldopa produces fall in BP in patients with hypertension. Like clonidine, it produces decrease in cardiac output
and peripheral resistance.

• It does not produce postural hypotension and does not reduce glomerular filtration or renal blood flow. It cause Na+
retension and hence, tolerance may develop to antihypertensive action after prolonged use. Diuretics enhance its action.

• Pharmacokinetics :

• On oral administration about 50% of the drug is absorbed. The peak effect is achieved after 2 to 4 hours. The drug is
completely excreted in urine after 12 hours. Drug may get accumulated if there is impaired renal function.
• Adverse effects: Sedation, headache, fatigue, drowsiness, forgetfullness, nightmares and mental depression are
common adverse effects. Rarely, it may produce fever, g.i. tract upset, nasal congestion, arthralgia (pain in joint) and
failure in ejaculation.

• Interactions: Tricyclic antidepressants reverse its action by blocking its active transport into the adrenergic neurones.
• Use: Methyldopa was a widely used antihypertensive, especially in combination with a diuretic. However, it is
infrequently used now, except to treat hypertension during pregnancy wherein it has a long track record of safety,
both for the mother as well as the foetus.

• ADRENERGIC NEURONE BLOCKERS

• RESERPINE:

• It is the alkaloid obtained from the root of Rouwolfia serpentina.

• Mechanism of Action : It causes depletion of catecholamines (adrenaline and noradrenaline) and other neurotransmitters such as
5-hydroxytryptamine from various organs and thereby, decreases sympathetic tone. Decrease in sympathetic activity is
responsible for the antihypertensive action of reserpine.

• Pharmacological Actions: Reserpine is the most potent antihypertensive agent. The effect appears after 30 minutes of i.v. injection
whereas, on oral administration it develops after 2-4 hours. The effect remains even after the cessation of the therapy.

• It also produces bradycardia, decrease in cardiac output and peripheral resistance as well as produces postural hypotension.

• Besides potent antihypertensive effect, it possesses antipsychotic action and sedation. It also increases gastric acid secretion and
peristalsis.
• Pharmacokientics: It is readily absorbed from g.i. tract and distributed fairly in CNS.
• Adverse effects: Excessive salivation, cutaneous vasodilatation, nasal congestion, increased gut motility,
bradycardia and increased gastric acid secretion are the effects produced by the sympathetic blockade.
• Because of the blockade of vasomotor reflexes (baroreceptors) it also cause postural hypotension.
• Because of central effects, reserpine produces drowsiness, water retention, mental depression, parkinsonism,
gynecomastia and impotence.

•VASODILATORS
• Hydralazine/Dihydralazine It is a directly acting arteriolar vasodilator with little action on venous capacitance
vessels; reduces t.p.r.

• The mechanism of vascular smooth muscle relaxant action of hydralazine is not clearly known. It is partly
endothelium dependent: may involve generation of NO (nitric oxide) and stimulation of cGMP. Direct effects on
membrane potential and on Ca2+ fluxes have also been proposed.
• Pharmacokinetics Hydralazine is well absorbed orally, and is subjected to first pass metabolism in liver.

• Bioavailability is higher in slow acetylators, but these patients are more prone to develop the lupus syndrome
(autoimmune disease).

• Hydralazine is completely metabolized both in liver and plasma; the metabolites are excreted in urine, t½ 1–2 hours.
However, hypotensive effect lasts longer (12 hours), probably because of its persistence in the vessel wall.
• Adverse effects are frequent and mainly due to vasodilatation.
• 1. Facial flushing, conjunctivitis, throbbing headache, dizziness, palpitation, nasal stuffiness, fluid retention, edema, CHF.
• 2. Angina and MI may be precipitated in patients with coronary artery disease.
• 3. Paresthesia (an abnormal sensation), tremor, muscle cramps, rarely peripheral neuritis.
• 4.Rheumatoid arthritis like symptoms develop on prolonged use of doses above 100 mg/day. It is more common in women
and in slow acetylators. It is slowly reversible on stopping treatment.
• Use: Hydralazine is used in moderate-to-severe hypertension not controlled by the first line drugs.

• Usually, low doses are added to the diuretic and β blocker already being administered. It is not used alone. Large doses are not
recommended for long periods.

• Hydralazine can be used in patients with renal involvement, but is contraindicated in older patients and in those with ischaemic
heart disease.

• It is one of the preferred antihypertensives during pregnancy because of decades of experience and record of safety. It can also be
used parenterally in hypertensive emergencies.

• Minoxidil :
• It is a powerful arterial vasodilator acting by potassium channel opening with potentially serious side effects.

• Major side effects are compensatory tachycardia, pulmonary, hypertension, hypertrichosis headache, pericardial effusion etc.

• It also causes hair growth. Thus minoxidil topical preparation (1-3%) are used to treat alopecia or baldness.

• It causes increase in dermal blood flow and elongation of follicles in the area of alopecia.
• Sodium Nitroprusside:
• Although sodium nitroprusside has been known since 1850 and its hypotensive effect in human
beings was described in 1929.
• Several investigators subsequently demonstrated that sodium nitroprusside also was effective in
improving cardiac function in patients with left ventricular failure.
• Mechanism of Action: Nitroprusside is a nitrovasodilator that acts by releasing nitric oxide (NO).
Production of NO by vascular endothelial cells activates the guanylyl cyclase-cyclic GMP-PKG
pathway, leading to vasodilation.

• The mechanism of release of NO is not clear and likely involves both enzymatic and nonenzymatic
pathways. Tolerance develops to nitroglycerin but not to nitroprusside.
• Pharmacological Effects: Nitroprusside dilates both arterioles and venules, and the hemodynamic
response to its administration results from a combination of venous pooling and reduced arterial
impendence (blood flow capacity of artery is decrease even force applied).
• In subjects with normal left ventricular function, venous pooling affects cardiac output more that
does the reduction of afterload; cardiac output tends to fall.
• In contrast, in patients with severely impaired left ventricular function and diastolic ventricular
distention, the reduction or arterial impedance is the predominant effect, leading to a rise in cardiac
output.
• Sodium nitroprusside is a nonselective vasodilator, and regional distribution of blood flow is little affected by
the drug.

• Unlike minoxidil, hydralazine, diazoxide, and other arteriolar vasodilators, sodium nitroprusside usually
causes only a modest increase in heart rate and an overall reduction in myocardial demand for oxygen.
• Absorption, Metabolism, and Excretion: Sodium nitroprusside is an unstable molecule that decomposes
under strongly alkaline conditions or when exposed to light.
• The drug must be given by continuous intravenous infusion to be effective.
• Its onset of action is within 30 second; the peak hypotensive effect occurs within 2 minutes, and when the
infusion of the drug is stopped, the effect disappears within 3 minutes.

• Therapetic Uses: Sodium nitropruside is used primarily to treat hypertensive emergencies, but can also be
used in many situations when short-term reduction of cardiac preload and/or afterload is desired.
• Nitroprusside has been used to lower blood pressure during acute aortic dissection, to improve cardiac
output in congestive heart failure, especially in hypertensive patients with pulmonary edema that does not
respond to other treatment and to decrease myocardial oxygen demand after acute myocardial infarction.
• In addition, nitroprusside is used to induce controlled hypotension during anesthesia in order to reduce
bleeding in surgical procedures.

• Adverse effect: Due to excessive vasodilation, hypotension generally occurs.