Transcription of PHARMACOTHERAPY OF HYPERTENSION
1 PHARMACOTHERAPY OF HYPERTENSION Dr. R. Jamuna Rani MD,Professor & HOD,Department of PharmacologyINTRODUCTION 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 over activity, renin angiotensin, aldosterone system and endothelium derived autocoids play a major role in the development of HYPERTENSION NON PHARMACOLOGICAL LINE OF TREATMENTR eduction of body restriction 5 exercise (meditation and yoga).Avoid smoking and alcohol. AVOID CURRY, HURRY AND Before 1950 veratrum and sodium thiocyanate were 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 ACE INHIBITORSC aptopril, Enalapril, Lisinopril, Ramipril, Benazepril, perindoprilDoes not affect the quality of 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 MECHANISM OF ACTION Angiotensin IACE inhibitors ACE Angiotensin converting enzyme Angiotensin II ADVERSE EFFECTS Brassy cough.
2 Angiooedema Hypotension Hyperkalemia Acute renal failure Fetopathic potential Proteinuria Loss of taste (dysgeusia)Neutropenia Common in collagen vascular disease or renal parenchymal disease 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 ( )ACE inhibitors increase plasma levels of digoxin and lithium (dosage adjustment is necessary)Increase hypersensitivity reactions to : Bilateral renal artery stenosis and pregnancy USESH ypertension Left ventricular dysfunction Acute myocardial infarction Patient who are at high risk of cardiovascular events Chronic renal failureScleroderma renal crisisANGIOTENSIN ANTAGONIST Losartan potassium, Irbesartan, candesartan, valsartan Angiotensin II receptor antagonist.
3 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 USESAll 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 hypertensionCALCIUM 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. 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 ALPHA blockers Phentolamine, phenoxybenzamine, prazosin, terazosin and doxazosin Side effects: Hypotension, tachycardia, nasal stuffiness, diarrhoea, miosis and impotenceUses: HYPERTENSION with benign enlargement of prostate PheochromocytomaALPHA & BETA BLOCKERSL abetalolCarvedilol also has antioxidant action Uses.
4 Hypertensive emergency, idiopathic dilated cardiomyopathy ALPHA METHYL DOPA Drug of choice for HYPERTENSION in pregnancy Activate alpha2receptors (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 CLONIDINEA lpha2agonist used in moderate HYPERTENSION . Sudden withdrawal cause rebound HYPERTENSION CPZ and TCA abolish antihypertensive action of clonidine Dose: 100mcg THIAZIDESC hlorthalidone, 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 hyperuricemiaVASODILATORS 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.
5 Also cause palpitation, lactic acidosis, vomiting & pain abdomen. NEW DRUGS Ambrisentan and Bosentan endothelin receptor antagonist used in pulmonary HYPERTENSION Fenoldopam ( infusion) selective D1 receptor agonist for short term management of severe HYPERTENSION Moxonidine Alpha2 agonist produce less sedationAliskiren Renin inhibitors
