A/p-adrenergic receptor antagonists

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

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. 

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... 

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. 

MYOCARDIAL INFARCTION There is no evidence that Ca + channel antagonists are beneficial in the early treatment or secondary prevention of acute Ml. In several trials, higher doses of the short-acting formulation of the dihydropyridine nifedipine had a detrimental effect on mortality. Diltiazem and verapamil may reduce the incidence of reinfarction in patients with a first non-ST segment elevation infarction who are not candidates for a fl adrenergic receptor antagonist, but P blockers remain the preferred drugs. 

Epinephrine can produce severe hypertension when used with a nonselective P receptor antagonist due to the unopposed stimulation of a receptors when vascular receptors are blocked. Such paradoxical hypertensive responses to p adrenergic receptor antagonists have been observed in patients with hypoglycemia or pheochromocytoma, during withdrawal from clonidine, following administration of Epi as a therapeutic agent, or in association with the iUicit use of cocaine. 

Guan, X.-M., Peroutka, S.J. and Kobilka, B.K. (1992) Identification of a single amino acid residue responsible for the binding of a class of P-adrenergic receptor antagonists to 5-hydroxytryptamineiA receptors. Mol. Pharmacol. 41 695-698. 

P adrenergic receptor antagonist, i heart rate, contractility and automaticity. Prolongs A-V conduction time and refractoriness. 

Bufuralol is a nonselective (3-adrenoreceptor blocking agent of comparable potency to propranolol. It has proven to be effective in treating hypertension and is a potent nonselective p-adrenergic receptor antagonist. Similarly to the method described earlier in Scheme 57.9, an efficient chemoenzymatic synthesis of (/ )-bufuralol has been reported involving a DKR of the chlorohydrin key intermediate rac-44 (Scheme 57.10). ... 

A. Miklavc, D. Kocjan, J. Mavri, J. Roller and D. Hadzi, On the fundamental difference in thermodynamics of agonist and antagonist interactions with P-adrenergic receptors and the mechanism of entropy-driven binding. Biochem. Pharmacol., 40 (1990) 663-669. 

Ono H, Mishima A, Ono S, Fukuda H, Vasko MR (1991) Inhibitory effects of donidine and tizanidine on release of substance P from slices of rat spinal cord and antagonism by a-adrenergic receptor antagonists. Neuropharmacology 30, 585-589... 

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