A REVIEW ON CHEMISTRY OF ANTIHYPERTENSIVE DRUGS

By Miss. Snehal .D. Karale. 2011-2012 Guided by Mr.Rajendra Patil. (M.Pharm.)

Contents:

Introduction Antihypertensive drugs Treatment of hypertension Hypertension urgencies &emergencies Complications of hypertension Conclusion

IntroductionHypertension or high blood pressure is a condition in which the blood pressure in the arteries is chronically elevated. With every heart beat, the heart pumps blood through the arteries to the rest of the body.

The antihypertensives are a class of drugs that are used high blood pressure.

There are many classes of antihypertensives, among the most important and most widely used are the thiazide diuretics, the ACE inhibitors, the calcium channel blockers, the beta blockers, and the angiotensin II receptor antagonists or ARBs.

 

.

The factors such as t.p.r.,heart rate & myocardial contractility are directly under the control of sympathetic nervous system which is supposed to be defective in a hypertensive patient.

According to clinical courses, primary & secondary hypertension may be benign or malignant.

Classification of Hypertension

ClassificationSystolic

(mmHg)

Diastolic

(mmHg)

Normal <120 <80

Prehypertension 120-139 80-89

Stage 1 140-159 90-99

Stage 2 >160 >100

Introduction To Antihypertensive DrugsClassification of antihypertensive drugs:

1. ADRENERGIC NEURON BLOCKING DRUGS:Bethanidine, Methoserpidine, Reserpine, Syrosingopine, Guanethedine

2. VASODILATORS:

a) Arterial Vasodilator : Hydralazine , Nifedipine Diazoxide , Minoxidil .

b) Veno vasodilator: GTN , Glycerine dinitrite .

c) Mixed Vasodilator : Sodium Nitropruside , ACE Inhibitor, Prazosin .

3.CENTRALLY ACTING SYMPATHOLYTIC ANTIHYPERTENSIVE DRUGS:

Clonidine,Guanabenz,labetalol,methyl dopa.

 

DIURETICS:

Diuretics

Thiazides

Hydrochlorothiazide

Chlorthalidone

Chlorothiazide

Indapamide

Metolazon

Potassium Sparing

Amiloride

Spironolactone

Triamterene

Loop Diuretics

Furosemide

Bumetanide

Ethacrynic acid

Torsemide

5.CALCIUM CHANNEL BLOCKER:

Calcium Channel Blockers

Dihydropyridines

o Amlodipine

o Nimodipine

o Isradipine

o Nicardipine

Non-dihydropyridines

o Bepridil

o Diltiazem

o Verapamil

 

6. DRUGS ACTING ON RENIN ANGIOTENSIN SYSTEM

a. ACE inhibitors:Benazepril, Captopril, Enalapril, Fosinopril, Lisinopril, Moexipril, Perindopril, Quinapril, Ramipril, Trandolapril

b. Angiotensin II receptor antagonist:Candesartan cilexetil, Losartan, Saralasin, Valsartan

7. DRUGS ACTING ON SEROTONIN RECEPTORS:Ketanserin, Urapidil

8. GANGLIONIC BLOCKING AGENTS:Mecamylamine hydrochloride, Pentamethonium bromide, Pentolinium, Trimethaphan camsylate

9. MONOAMINE OXIDASE INHIBITOR:Pargyline hydrochloride

10.PERIPHERAL ANTIADRENERGIC DRUGSa. α-blockers:Phenoxybenzamine, Phentolamine, b. α1-blockers:Doxazosin, Prazosin, Terazosinc. β-blockers:Atenolol, Metoprolol, Nadolol, Propranolol, Timolold. α and β blockers:Labetalol

11. MISCELLANEOUS:Bretylium

Adrenergic neuron blocking drugs

Bethanidine Bethanidine

Mechanism of action:

It is a peripherally acting anti adrenergic agents Potent drugs that block nor adrenaline form sympathetic nerve endings a decrease in nor adrenaline decrease in BP

Adverse effects:Diarrhoea,nasal congestion,postural hypoension.

Antihyptensive direct vasodilators

Mechanism of action:

Opening of potassium channel.

Adverse effects:salt and water retention and hyperglycemia. Inhibits insulin release. HypogammaglobulinaemiaDizzinessHyperglucaemia & transient diabetes mellitus

Diazoxide

 Centrally acting sympatholytic antihypertensive

Mechanism of action:Stimulate Alpha-2 receptors decrease sympathetic activity decrease adrenaline, nor adrenaline & decrease peripheral vascular resistance.Decreased NE-vasodilation-Decreased TPR

Adverse Effects:Dry mouth Sedation Impotence

Clonidine

Calcium channel blockers

Verapamil l

Mechanism of action:

Inhibits voltage-dependent

calcium channels

Adverse effects:Dizziness.Facial flushing.Headache.Edema.Hemorrhagic gingivitis.

Na+

Ca++

Diuretics

Mechanism of action Promote Na+ depletion decrease in extra cellular fluid Increase renal blood flow by decreasing renal vascular resistance.

Adverse Effects Hypomagnesemia Hypocalcaemia.

Furosemide

Drugs acting on Renin angiotensin system

Mechanism of action: (ACEinhibitors)Prevents conversion of Angiotensin I to angiotensin II & blocks release of aldosterone. Aldosterone promotes Na+ retention & K+ excretion. Na+ excreted, but water & K retained.

Adverse Effects Angioedema,Dry cough.

Benazeprilat

Ganglionic blocking agents

Mechanism of action:

Prevents stimulation of postsynaptic receptors by acetylcholine released from presynaptic nerve endings.

Adverse effects: Hypotension, paralytic ileus Urinary retention. Cycloplegia.

Mecamylamin Hydrochloride

Mechanism of action(α-blockers)

It blocks alpha receptors.

Adverse EffectsTachycardiaConfusion Drowsiness, headache Dryness of mouth Sexual problems in males Unusual tiredness or weakness

Phenoxybenzamine

α1-blockers

Blocking -receptors on vascular smooth muscle allows muscle relaxation, dilation of vessel, and reduced resistance.

β-blockers

Like metoprolol, atenolol competes with sympathomimetic neurotransmitters such as catecholamines for binding at beta(1)-adrenergic receptors in the heart and vascular smooth muscle, inhibiting sympathetic stimulation.

Treatment for Hypertension

Commonly used drugs include:ACE inhibitors Angiotensin II receptor antagonistsAlpha blockers Beta blockers Calcium channel blockers Diuretics

Fixed drug combinations β blockers + ThiazideACE inhibitors + Thiazide Calcium channel blockers + ACE inhibitorARB + Diuretics

ComplicationsCerebrovascular accident Myocardial infarctionHypertensive cardiomyopathyHypertensive retinopathy Hypertensive nephropathy

Hypertension in pregnancySafer antihypertensive drugsMethyldopaLabetalol HydralazinePrazosin Clonidine

ContraindicationsACE inhibitorsAngiotensin II receptor blockersBeta-blockersVasodilator

Hypertensive urgencies and emergencies

Cardio vascular accidentHypertensive encephalopathyMIAcute renal failureDissecting aortic aneurysmEclampsiaHypertensive crisis in cheese reaction & pheochromocytoma

CONCLUSION

BP normalization is crucial to reduce the Cardiovascular risk of hypertensive patients. BP reduction is a fairly easy target, BP normalization is much more difficult to achieve. One of the main reasons for the lack of efficacy of pharmacological treatment is that drugs are very often not administered at the correct dosage.

THANK YOU