Regarding ACE inhibitor which of the following is trueaEUR'
Omission of prior diuretic dose decreases the risk of postural hypotension Angiotensin conveing enzyme inhibitors Renin is an enzyme produced by the kidney in response to sodium depletion and increased adrenergic activity. Renin conves a circulating glycoprotein (angiotensinogen) into the biologically ine angiotensin I, which is then conveed by angiotensin conveing enzyme (ACE or kininase II) into the highly potent vasoconstrictor Angiotensin II. Angiotensin conveing enzyme or (ACE) is located on the luminal surface of capillary endothelial cells, paicularly in the lungs. Angiotensin II exes its effect by acting on two receptors i.e. ATi and AT2. Main actions of Angiotensin II a)Vasoconstriction Angiotensin II is the most potent vasoconstrictor in the body. It increases total peripheral resistance by constricting precapillary aerioles and to a lesser extent postcapillary venules by activating ATi receptors. Angiotensin II also produces peripheral vasoconstriction by enhancement of peripheral noradrenergic neurotransmission. b) Release of Aldosterone from adrenal coex Angiotensin II stimulates the zona glomerulosa of the adrenal coex to increase the synthesis and secretion of aldosterone. c) Altered renal hemodynamics Angiotensin II variably influences glomerular filtration rate several mechanisms - i) Constriction of the afferent aerioles which reduces intraglomerular pressure and tends to reduce GFR. ii) Contraction of measangial cells which decreases the capillary surface area which reduces GFR. iii) Constriction of efferent aerioles which increases intraglomerular pressure and tends to increase GFR. - The outcome of these opposing effects on GFR depends upon the physiological state :- Normally G.F.R is slighthy reduced by angiotensin II. d) Effect of Angiotensin II on cardiac structure :- i) Increased wall to lumen ratio in blood vessels ii) Concentric cardiac hyperophy iii) Eccentric cardiac hyperophy iv) Thickening of intimal surface of blood vessels ACE inhibitors ACE inhibitors are drugs which exe their action by inhibiting the conversion of Angiotensin Ito Angiotensin R. They inhibit the angiotensin conveing enzyme. Example of ACE inhibitors:? Captopril Enalapril Lisinopril Ramipril Trandolapril Perindropil Therapeutic uses of ACE inhibitors:? ACE inhibitors in hypeension Inhibition of ACE lowers systemic vascular resistance. ACE inhibitors lower mean, diastolic and systolic blood pressure in various hypeensive states. The initial change in blood pressure is directly related to plasma renin activity. Elevated plasma renin activity renders patients hyperre.sponsive to ACE inhibitor induced hypotension and initial dosages of all ACE inhibitors should he reduced in patients with high plasma level of renin (e.g. patients with hea failure and salt depleted patients). ACE inhibitors in left ventricular systolic dysfunction ACE inhibitors should be given to all patients with impaired left ventricular systolic .function. Although the mechanism by which ACE inhibitors improve outcome in patients with systolic dysfunction are not completely understood, the induction of a more ourable hemodynamic state most likely plays an impoant role. Inhibition of ACE commonly reduces afterload and systolic wall stress, and both cardiac output and cardiac index increases as do indices of stroke work and stroke volume. There is over whelming evidence that ACE inhibitors should be used in symptomatic and asymptomatic patients with a depressed Ejection fraction (< 40%). Although the role of ACE inhibitors in left ventricular systolic dysfunction is firmly established whether these drugs improve diastolic dysfunction is an impoant open question. Infusion of enalaprilat into the left coronary aeries of patients with left ventricular hyperophy significantly improves diastolic function. Remember, This impoant point about the use of ACE in hea failure. Severe hypotension may result in patient taking diuretics or who are hypovolemic, hyponatremic, elderly, have renal impainnent or with systolic blood pressure < 100 minHg. A test dose of captopril 6.25 mg by mouth may be given because its effect lasts only 4-61t. If tolerated, the preferred long acting ACE inhibitor may then be initiated in low dose. ACE inhibitors in myocardial infarction Several large prospective, randomized clinical studies involving thousands of patients provide convincing evidence that ACE inhibitors reduce overall moality when treatment is begun during peri-infarction period. ACE inhibitors in chronic renal failure Diabetes mellitus is the leading cause of renal disease. In patients with type I diabetes mellitus and diabetic nephropathy captopril prevents or delays the progression of renal disease. Specific renoprotection by ACE inhibitors is more di'. ficult to demonstrate in type 2 diabetics. Several mechanisms paicipate in renal protection afforded by ACE inhibitors. Increased glomerular capillary pressure induces glomerular injury and ACE inhibitors reduce this parameter both by decreasing aerial blood pressure and by dilating renal efferent aerioles. Adverse effect of ACE inhibitors Hypotension A steep fall in blood pressure may occur following the first dose of an ACE inhibitor in patients with elevated PRA (plasma renin activity). In this regard, care should he exercised in patients who are - Salt depleted - In patients being treated with multiple antihypeensive drugs, - In patients who have congestive hea. failure - In patients who are on diuretics. The doses of ACE inhibitors should be initiated in low doses followed by gradual increment if the lower doses have been well tolerated. Pharmacokinetics All ACE inhibitors except captopril and lisinopril are prodrugs and are conveed to the active agents by hydrolysis primarily in the liver. Enalapril is an oral prodrug that is conveed by hydrolysis in liver to an active form Enalaprilat. Enalaprilat itself is available only for intravenous use primarily for hypeensive emergencies. Enalapril has a half life of only 1.3 hours but enalaprilat because of tight binding to ACE has a plasma half life of about 11 hours. Lisinopril is the lysine analogue of enalapril. Unlike enalapril, Lisinopril itself is active and its half life in plasma is about 12 hours. All ACE inhibitors are cleared as the intact compound by the kidney (except fosinopril and moexipril).
Inhibits conversion of angiotensinogen to arigiotensin I
T 1/2 of enalapril is more than lisinoproil
Omission of prior diuretic dose decreases the risk of postural hypotension
It is effective only with left ventricular systolic dysfunction