pharmacotherapy of hypertension - srm · pdf filepharmacotherapy of hypertension dr. r. jamuna...
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PHARMACOTHERAPY OF HYPERTENSION
Dr. R. Jamuna Rani MD,Professor & HOD,
Department of Pharmacology
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INTRODUCTION
Hypertension is a common disorder if not effectively treated results in coronary thrombosis, stroke, retinopathy and renal failure Blood pressure is intimately related to kidneys – renovascular hypertension.Sympathetic over activity, renin angiotensin, aldosterone system and endothelium derived autocoids play a major role in the development of hypertension
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NON PHARMACOLOGICAL LINE OF TREATMENT
Reduction of body weight.Sodium restriction 5gms/day.Potassium therapy.Physical exercise.Relaxation exercise (meditation and yoga).Avoid smoking and alcohol. AVOID CURRY, HURRY AND WORRY.
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HISTORY Before 1950 veratrum and sodium thiocyanate were used.1950 – Ganglion blocker, reserpine and hydralazine 1960 – 1970 – Guanethidine, Beta blockers, Alpha blockers, Alpha methyldopa, clonidine and diuretics 1980 – 1990 – ACE inhibitors and calcium channel blockers 1992 – Angiotensin1 receptor antagonist
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ACE INHIBITORS
Captopril, Enalapril, Lisinopril, Ramipril, Benazepril, perindoprilDoes not affect the quality of life.First line drug in the treatment of hypertension Safe in asthma, diabetes mellitus and peripheral vascular diseases Renal blood flow is well maintained Prevent left ventricular remodeling, vascular hypertrophy and secondary hyperaldosteronism
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MECHANISM OF ACTION
Angiotensin I
ACE inhibitors ACE Angiotensin converting enzyme
Angiotensin II
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ADVERSE EFFECTS Brassy cough, Angiooedema Hypotension Hyperkalemia Acute renal failure Fetopathic potential Proteinuria Loss of taste (dysgeusia)Neutropenia – Common in collagen vascular disease or renal parenchymal disease
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DRUG INTERACTIONS
Antacids reduce the bioavailability of ACE inhibitors NSAIDs reduce anti hypertensive effect of ACE inhibitors K+ sparing diuretics and K+ supplement exacerbate ACE inhibitor induced hyperkalemia
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(Contd…)
ACE inhibitors increase plasma levels of digoxin and lithium (dosage adjustment is necessary)Increase hypersensitivity reactions to allopurinol.Contraindications: Bilateral renal artery stenosis and pregnancy
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USES
Hypertension Left ventricular dysfunction Acute myocardial infarction Patient who are at high risk of cardiovascular events Chronic renal failureScleroderma renal crisis
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ANGIOTENSIN ANTAGONIST
Losartan potassium, Irbesartan, candesartan, valsartan Angiotensin II receptor antagonist; losartan block the AT1 receptors competitively and the metabolite E3174 irreversibly inhibits AT1 receptor Brassy cough is less common Adverse effects, contraindications and drug interaction are similar to ACE inhibitors
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USES
All angiotensin II receptor antagonist are approved for the treatment of hypertension Irbesartan and losartan are approved for diabetic retinopathyValsartan is approved for heart failure Losartan is approved for stroke prophylaxis and cirrhosis with portal hypertension
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CALCIUM CHANNEL BLOCKERS
Nifedipine, amlodipine, felodipineThey block voltage sensitive L – type calcium channels Side effects: Headache, hypotension, reflex tachycardia and ankle oedemaUses: Idiopathic systolic hypertension , cyclosporine induced hypertension, and in pregnancy – discontinue before labour.
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BETA BLOCKERS Propranolol, timolol, atenolol, acebutalol and metaprolol First line drug in hypertension Less effective in elderly patients Side effects: Bradycardia, cause rebound hypertension on sudden withdrawal Fatigue sleep disturbances and depression Propranolol mask the hypoglycemic symptoms produced by insulin and oral hypoglycemic agentsC/I: Bronchial Asthma
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ALPHA BLOCKERS
Phentolamine, phenoxybenzamine, prazosin, terazosin and doxazosin Side effects: Hypotension, tachycardia, nasal stuffiness, diarrhoea, miosis and impotenceUses: Hypertension with benign enlargement of prostate Pheochromocytoma
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ALPHA & BETA BLOCKERS
LabetalolCarvedilol – also has antioxidant action Uses: hypertensive emergency, idiopathic dilated cardiomyopathy
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ALPHA METHYL DOPA
Drug of choice for hypertension in pregnancy Activate alpha2 receptors (presynaptic) and decrease norephinephrine release Side effects: Sedation, hypotension, hypersensitivity, nasal stuffiness, weight gain Produce positive coomb’s testTricyclic antidepressants reverse its effect Dose: 250mg – 500mg b.d
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CLONIDINE
Alpha2 agonist used in moderate hypertension. Sudden withdrawal cause rebound hypertension CPZ and TCA abolish antihypertensive action of clonidine Dose: 100mcg b.d
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THIAZIDES
Chlorthalidone, hydrochlorothiazide Used in mild hypertension and effective in elderly patients It potentiate the action of all antihypertensive drugs except calcium channel blockers Side effects: Hypokalemia, hyponatremia, hypomagnesemia, hyperglycemia, hypercalcemia and hyperuricemia
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VASODILATORS
Hydralazine – useful in pregnancy Minoxidil – Alopecia (male type baldness)Diazoxide – In operable insulinomasSodium nitropruside Balanced vasodilator, produce vasodilatation by activating glutathione and release NO used in hypertensive emergency produce controlled hypotension if it is administered continuously release cyanide and latter converted to thiocyanate and cause psychosis. Also cause palpitation, lactic acidosis, vomiting & pain abdomen.
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NEW DRUGS
Ambrisentan and Bosentan – endothelin receptor antagonist used in pulmonary hypertension Fenoldopam – (I.V infusion) selective D1 receptor agonist for short term management of severe hypertension Moxonidine – Alpha2 agonist produce less sedationAliskiren – Renin inhibitors
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