Angiotensin receptors antagonists

PROFESS is an ongoing large randomized trial examining combination ER-DP plus aspirin therapy compared with clopidogrel (each group also with or without telmisartan, an angiotensin receptor antagonist) for the secondary prevention of early and late recurrent stroke, and other vascular events. 

Angiotensin II causes vasoconstriction by direct stimulation of ATj receptors on the vascular smooth muscle. It also enhances release of the neurotransmitter norepinephrine from the sympathetic nerve fibers present in the blood vessels. The vasopressor effects of Ag II may be inhibited pharmacologically in order to decrease TPR and treat hypertension. An important class of orally active drugs is the ACE inhibitors, including captopril and enalopril, which prevent formation of Ag II. More recently, angiotensin receptor antagonists have been developed that act at the vascular smooth muscle. These drugs, which include losartin and valsartan, are also orally active. 

Renal function impairment In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (eg, patients with severe CHF), treatment with ACE inhibitors and angiotensin receptor antagonists has been associated with oliguria or progressive azotemia and with acute renal failure or death (rarely). No dosage adjustment is necessary for patients with renal impairment unless they are volume-depleted. AIIRAs are not dialyzable. 

Angiotensin receptor antagonists were developed through modification of the angiotensin molecule. The most effective compound is the [Sar, VaP, Ala ] angiotensin II, called saralasin (5.145) (sar = sarcosine = N-methylglycine). Unfortunately, the peptidic... 

Paradoxically, these agents—not positive inotropic drugs—are the first-line therapies for chronic heart failure. The drugs most commonly used are diuretics, ACE inhibitors, angiotensin receptor antagonists, aldosterone antagonists, and blockers (Table 13-1). In acute failure,... 

Cruden NL, Newby DE. Angiotensin antagonism in patients with heart failure AGE inhibitors, angiotensin receptor antagonists or both Am J Cardiovasc Drugs. 2004 4 345-353. 

Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Antagonists, Related Agents... 

Preparations of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists are found in Chapter 11 Antihypertensive Agents preparations of vasopressin are found in Chapter 37 Hypothalamic Pituitary Hormones. 

Presynaptic Angiotensin Heteroreceptors Angiotensin Receptor Antagonists.567... 

Saralasin 71 is currently in use as an angiotensin-receptor antagonist in the treatment of hypertension, despite its partial agonistic effect. The disadvantages of 71 lie in the fact that it is administered i.v. and in its short biological half-life. 

Lewis EJ, Hunsicker LG, Clarke WR et al. (2001) Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to Type 2 diabetes. New England journal of Medicine 345 851-860. 

Q9 An alternative to the ACE inhibitors is an angiotensin receptor antagonist such as losartan or valsartan. This class of drug also acts on the renin-angiotensin system and appears to offer all the advantages of ACE inhibitors, without causing the dry cough which Sam found unacceptable. 

The results of SPICE (The Study of Patients Intolerant of Converting Enzyme Inhibitors) and of the previously published RESOLVD led to the design of the current CHARM trial, which is investigating the effect of candesartan in 6600 patients with heart failure in three different ways versus an ACE inhibitor in patients with preserved left ventricular function versus placebo in patients intolerant of ACE inhibitors and in addition to ACE inhibitors in all other patients. While waiting for the results of this trial it is advisable to continue to use ACE inhibitors as the initial therapy for heart failure. In patients with documented intolerance of ACE inhibitors (which may represent 10-20% of patients with heart failure) angiotensin receptor antagonists may be useful as a substitute to block the renin-angiotensin-aldosterone system. 

Concurrent administration of potassium supplements, potassium-sparing diuretics, or salt substitutes can precipitate hyperkalemia in ACE inhibitor-treated patients, in whom aldosterone is suppressed (SED-14, 674). Regular monitoring of serum potassium is essential in these patients, because of the risk of hyperkalemia in patients given potassium (or potassium-sparing diuretics) and ACE inhibitors or angiotensin receptor antagonists. 

Hyperkalemia, due to potassium chloride, potassium-retaining diuretics, ACE inhibitors, or angiotensin-receptor antagonists, reduces the apparent affinity of digitalis for Na/K-ATPase and thereby reduces its tissue binding. 

Non-IgE-mediated anaphylactic reactions to polyacrylonitrile membranes have been reported (2,3). The effects are enhacing in those using ACE inhibitors (4,5), perhaps because of an effect of bradykinin (6), which is released by the membranes (2,8,9) and whose metabolism is inhibited by ACE inhibitors. The effects also occur to a lesser extent in those taking angiotensin receptor antagonists (7) and in those with Cl esterase inhibitor deficiency (10). Treating the membranes with polyethyleneimine prevents bradykinin release (11). 

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