ACE inhibitors Renin angiotensin and aldosterone play important

ACE inhibitors

• Renin, angiotensin, and aldosterone play important roles - essential hypertension Renin release stimulated by - reduced renal arterial pressure - sympathetic neural stimulation - reduced sodium delivery

Renin-angiotensin system. arteries Angiotensinogen AI AII Renin adrenal glands Aldosterone kidneys Na+

ACE inhibitors • Captopril, enalapril, lisinopril, benazepril, fosinopril, perindopril, ramipril. • Inhibits conversion of angiotension I to angiotension II. • Inhibits bradykinin - a vasodilator, which stimulates release of nitric oxide & prostacyclin

• bradykinin receptor antagonist, icatibant blunts BP lowering effect of captopril • Enalapril prodrug hydrolysed to enalaprilat primarily in the liver • Enalaprilat only for intravenous use in hypertensive emergencies. • Lisinopril is a lysine derivative of enalaprilat

• ↓BP ↓PVR. NO change in CO & HR • No reflex sympathetic activation • used safely in IHD (Unlike direct vasodilators ) • absence of reflex tachycardia – downward resetting of the baroreceptors – enhanced parasympathetic activity

• diminish proteinuria • stabilize renal function even in the absence of lowering of BP useful in chronic kidney disease • improved intrarenal hemodynamics ↓glomerular efferent arteriolar resistance ↓intraglomerular capillary pressure

Uses – ACE inhibitor • • Hypertension Heart failure Myocardial infarction Diabetic nephropathy

Adverse effects • • Hypotension Hyperkalemia Dry cough Angioedema Acute renal failure Dysguesia Rashes, urticaria fetopathic

Angiotensin receptor antagonists • Losartan, valsartan, candesartan, eprosartan, irbesartan, telmisartan − no effect on bradykinin metabolism Cough and angioedema less common − more complete inhibition of angiotensin action compared with ACE inhibitors; alternative enzymes generating angiotensin II. • benefits similar to ACE inhibitors in heart failure and chronic kidney disease. • adverse effects similar to ACE inhibitors including hazard of use during pregnancy.