CARBOXYPEPTIDASE INHIBITORS

CARBOXYPEPTIDASE INHIBITORS act against various members of carboxypeptidase enzyme family that cleave the C-terminal residue from oligopeptides or from proteins. They can be divided into classes on the basis of their functional characteristics. These classes are dealt with separately in terms of their alternate names, notable substrates and inhibitors. Most of these are thought to correspond to the metalloproteinase class of enzyme. There are a number of enzymes of special interest in relation to their neuropeptidase actions. Dipeptidyl carboxypeptidase A (EC 3.4.15.1; angiotensin-converting enzyme; ACE; kininase II) is a much-studied zinc-metalloproteinase, cleaving the last two carboxyterminal residues of peptides. It has a wide distribution and is found in a membrane-bound form, notably on vascular endothelial cells and in plasma. Notable substrates include angiotensin I (converted to an active product, angiotensin II), bradykinin, cholecystokinin, gastrin, leucine-enkephalin, methione-enkephalin, LH-RH, neurotensin and substance P. Inhibitors include the large family of ACE inhibitors used in therapeutics as antihypertensives. Examples in clinical use include captopril, cilazapril, enalapril, fosinopril, lisinopril, Read more […]

ACE INHIBITORS

ACE INHIBITORS (angiotensin-converting enzyme inhibitors) act by inhibiting the enzyme EC 3.4.15.1, variously known as angiotensin-converting enzyme (ACE), kininase II, dipeptidyl peptidase A. This peptidase, found in vascular endothelial cells and plasma, converts, by carboxyterminal dipeptidyl cleavage, the circulating vascular hormone angiotensin from its inactive decapeptide form angiotensin I, to the active octapeptide form, angiotensin II. Since angiotensin II is a very potent vasoconstrictor, the effect of ACE inhibitors is to cause vasodilatation with an overall hypotensive effect. Such drugs can be used as ANTIHYPERTENSIVES, and also in HEART FAILURE TREATMENT. However, drugs of this class have a number of side-effects (in particular an irritating cough), some of which can be attributed to the fact that ACE inhibitors necessarily prolong the duration of action of, and so potentiate, bradykinin. This sensory nerve activator and hypotensive hormone is degraded to an inactive dipeptidyl cleavage product by the same enzyme (in the kinin context commonly referred to as kininase II). ACE inhibitor drugs were developed by modelling interaction with the active site of the enzyme of a snake-venom-derived bradykinin-potentiating Read more […]

ANTIHYPERTENSIVE AGENTS

ANTIHYPERTENSIVE AGENTS are used to reduce high blood pressure when it is raised in disease, though such drugs are not necessarily hypotensive (i.e. they may not lower blood pressure in normotensive subjects). Hypertension is an elevation of arterial blood pressure above the normal range expected in a particular age group, sex etc. It can have several different causes, which to some extent determine the treatment. Above certain values, after making lifestyle corrections, intervention with drug therapy may reduce the risk of heart attacks, kidney failure or a stroke, and may help in the treatment of angina pectoris. There are several large groups of drugs used as antihypertensives, each with a specific mode of action. DIURETICS are in common use as antihypertensives, and often a mild diuretic may be all that is required: e.g. amiloride. chtorothiazide, ethacrynic acid, frusemide, hydrochlorothiazide, spironolactone, triamterene. Beta-blockers, of which there are many, may be used if further treatment is necessary, with or without simultaneous administration of a diuretic: e.g. acebutolol, oxprenolol, propranolol and sotalol. See β-ADRENOCEPTOR ANTAGONISTS. Other antihypertensive drugs work as antisympathetic Read more […]