P-Adrenoceptor Blocking Agent

Propafenone. Propafenone hydrochloride, an arylketone, is stmcturaHy similar to the P-adrenoceptor blocking agents. It has been in use in the former West Germany since 1977 and was introduced in the United States in 1990. Its effects may result from a combination of weak calcium channel blocking, weak nonselective -adrenoceptor blocking, and sodium channel blocking activity. Propafenone is effective in treating supraventricular tachyarrhythmias, ventricular ectopic beats, and ventricular arrhythmias. It is the most frequendy prescribed medication for ventricular arrhythmias in Europe (32). 

Class II Antiarrhythmic Agents The p-Adrenoceptor Blocking Agents... 

Propranolol. Propranolol hydrochloride, considered the prototype of the P-adrenoceptor blocking agents, has been in use since 1964. It is a nonselective, highly Hpid-soluble P-adrenoceptor blocker having no ISA. It is a mixture of (+) and (—) enantiomers, and the (—) enantiomer is the active moiety. The local anesthetic effects of propranolol are equipotent to those of Hdocaine [137-58-6] C 4H22N20, (see Anesthetics). Therapeutic effects include termination of catecholamine-induced arrhythmias, conversion of SA nodal tachycardias (including flutter and fibrillation) and AV nodal tachyarrhythmias to normal sinus rhythm, digitahs-induced arrhythmias, and ventricular arrhythmias (1,2). The dmg also has cardioprotective properties (37,39). 

Other P"Adrenoceptor Blocking Agents. Several other p-adrenoceptor blocking agents are in development as antiarrhythmic agents. These include carteolol, flestolol, and bopindolol (see Table 1). 

Metoprolol. Metoprolol tartrate (Table 1), also a Class II antiarrhythmic agent, is a HpophiHc, cardioselective P -adrenoceptor blocking agent... 

Other P"Adrenoceptor Blocking Agents. Carteolol hydrochloride (Table 1) is also a Class II antiarrhythmic agent. In three separate studies in patients having angina pectoris, carteolol was considered effective as evidenced by a reduction in the frequency and severity of anginal episodes, reduction in the amount of nitroglycerin consumed, improvement of ECG parameters, or an increase in the duration of trea dmill exercise (42). 

Practolol (Figure 8.13) was the prototype cardioselective p-adrenoceptor blocking agent. Selectivity was achieved by substitution in the para position with an acetyl anilino function. The similarity of this drug with those outlined above is obvious. Practolol caused severe skin and eye lesions in some patients which led to its withdrawal from the market [6]. These lesions manifested as a rash, hyperkeratosis, scarring, even perforation of the cornea and development of a fibrovascular mass in the conjunctiva, and sclerosing peritonitis. Some evidence is available that the drug is oxidatively metabolized to a reactive product that binds irreversibly to tissue pro-... 

The cardiovascular response to dopamine in humans depends on the concentration infused. Low rates of dopamine infusion can produce vasodilation in the renal, mesenteric, coronary, and intercerebral vascular beds with little effect on other blood vessels or on the heart. The vasodilation produced by dopamine is not antagonized by the p-adrenoceptor blocking agent propranolol but is antagonized by haloperidol and other dopamine receptor-blocking agents. 

Long-term treatment with p-adrenoceptor blocking agents is clearly associated with an increased rate of... 

Verapamil must be used with extreme caution or not at all in patients who are receiving p-adrenoceptor blocking agents. Normally, the negative chronotropic effect of verapamil will in part be overcome by an increase in reflex sympathetic tone. The latter is be prevented by simultaneous administration of a p-adrenoceptor blocking agent, which exaggerates the depressant effects of... 

P-adrenoceptor blocking agents are used in hypertension of pregnancy, including pre-eclampsia. Both lipid- and water-soluble members enter the fetus and may cause neonatal bradycardia and hypo-glycaemia. They are not teratogenic in pregnancy. 

Steric Configuration and Polymorphic Oxidation of Lipophilic P-Adrenoceptor Blocking Agents in vitro-in vivo Correlations, Biochem. Pharmacol., 34 399-400. 

The P-adrenoceptor blocking agents (or P-blockers) have received an overwhelming cognizance in the therapeutic armamentarium in the past four decades that they have been judiciously classified into the following three categories, namely ... 

Craig Gugler R, Kreis L and Dengler HJ, Pharmacokinetics of a new p-adrenoceptor blocking agent, LF 17-895, in man, Arzneim.-Forsch., 25, 1067-1072 (1975). 

Epichlorohydrin is a substrate in the synthesis of P-adrenoceptor blocking agents and, together with oxprenolol and propranolol, was the cause, after... 

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