P-Adrenergic receptor antagonists

Clinically used p-adrenergic receptor antagonists ( P-blockers ) are either px-selective (e.g. bisoprolol, metoprolol, atenolol, betaxolol) or non-selective,... 

Non-selective P-adrenergic receptor antagonists (e.g. propranolol) can suppress tachycardia and tremor in patients with hyperthyroidism or tremor caused by... 

Vasodilators. Hydralazine causes direct relaxation of arteriolar smooth muscle. An important consequence of this vasodilation, however, is reflex tachycardia (T CO). It may also cause sodium retention (T plasma volume). The resulting increase in CO tends to offset effects of the vasodilator. Therefore, these drugs are most effective when administered along with sympathetic agents such as P-adrenergic receptor antagonists, which prevent unwanted compensatory responses by the heart. 

The answer is i. (Hardman, p 2312) Timolol is a p-adrenergic receptor antagonist that does not show selectivity for pi or p2 adrenoceptors ... 

Esmolol hydrochloride is a competitive p-adrenergic receptor antagonist it is selective for pT adrenoceptors. In contrast to pindolol, esmolol has little intrinsic sympathomimetic activity, and it differs from propranolol in that it lacks membrane stabilizing activity Of all of the p-adrenergic blocking drugs, this compound has the shortest duration of action because it is an ester, it is hydrolyzed rapidly by plasma esterases and must be used by the intravenous route Esmolol is approved only for the treatment of supraventricular arrhythmias... 

Fluorinated dihydroxyphenyl serine derivatives 48a and 48b, potential a- and p-adrenergic receptor antagonists, have been prepared from the corresponding fluorinated cinnamates 47a and 47b by the (DHQD)2AQN mediated AA [37] (Scheme 8). Reactions in propanol/water (1 1) gave the best results with respect to yield (76% and 38%) and enantioselectivity (86% and 82% ee). 

P-adrenergic receptor antagonists may also provide less benefit than other classes of antihypertensive drugs (45). Nevertheless, P-adrenergic receptor antagonists remain a widely accepted choice for the first-line treatment of hypertension. 

Drugs may slow automatic rhythms by altering any of the four determinants of spontaneous pacemaker discharge, increase maximnm diastolic potential, decrease phase 4 slope, threshold potential, or increase action potential duration. Adenosine and acetylcholine may increase maximum diastolic potential, and P-adrenergic receptor antagonist (P-blockers) may decrease phase 4 slope. Block of Na+ or Ca " channels usually results iu altered threshold, and block of cardiac K+ channels prolongs the action potential. 

Nicardipine has antianginal properties similar to those of nifedipine and may have selectivity for coronary vessels. Isradipine also produces the typical peripheral vasodilation seen with other dihydropyridines, but because of its inhibitory effect on the sinoatrial (SA) node, little or no rise in heart rate is seen. This inhibitory effect does not extend to the cardiac myocytes, however, because no cardiodepres-sant effect is seen. Despite the negative chronotropic effect, isradipine appears to have little effect on the atrioventri-cnlar (AV) node, so it may be used in patients with AV block or combined with a P-adrenergic-receptor antagonist. 

P Adrenergic receptor antagonists that lack intrinsic sympathomimetic activity improve mortality in MI. They should be given early and continued indefinitely in patients who can tolerate them. 

Task forces from the ACC and the AHA have published guidelines that are useful in the selection of appropriate initial therapy for patients with chronic stable angina pectoris (www.americanheart.org). Patients with coronary artery disease should be treated with aspirin and a P adrenergic receptor antagonist (particularly if there is a history of prior MI). The guidelines also... 

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