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). 

The electrophysiological effects of amiodarone may be a composite of several properties. In addition to prolonging action potential duration and refractory period in ad tissues of the heart, the compound is an effective sodium channel blocker (49), calcium channel blocker (50), and a weak noncompetitive -adrenoceptor blocking agent (51). Amiodarone slows the sinus rate, markedly prolongs the QT interval, and slightly prolongs the QRS duration (1,2). 

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

Nadolol. Nadolol (Table 3) is a hydrophilic, nonselective -adrenoceptor blocking agent having no ISA and no membrane-stabilizing activity. It is useful for the treatment of hypertension and chronic stable exertional angina (98,99,108). 

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). 

Barbato, E., Caliendo, G., Larotonda, M. L, Morrica, P., Silipo, C., Vittoria, A. Relationships between octanol-water partition data, chromatographic indices and their dependence on pH in a set of beta-adrenoceptor blocking agents. 

Inderal containing propranolol (beta-adrenoceptor blocking agent) is used with caution in diabetic patients. 

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 sympatholyfics of this type interfere with the /3i- and /S2-adrenoceptor subtypes. Via this mechanism the stimulating influence of the sympathetic nervous system on the heart and the metabolism and its inhibiting influence on smooth muscle is blocked. /3-Adrenoceptor blocking agents, or /3-blockers, mostly have a typical isoproterenol-like structure with an isopropylamine or a tertiary butylamine group and a substituted phenoxy moiety bound to the isopropanol backbone. The substituents determine the physicochemical properties of the particular drug and thereby its pharmacokinetic proflle. 

Clonidine is an agonist at a - and o 2-adreno-ceptor subtypes. It reduce the sympathetic tonus and is thereby a useful antihypertensive drug. Clonidine can induce sedation, depression and peripheral side effects like a dry mouth. Unspecific a-adrenoceptor blocking agents like tricyclic antidepressants can reduce the antihypertensice effect of clonidine. 

Van Zwieten PA. Alpha-adrenoceptor blocking agents in the treatment of hypertension. In Laragh JH, Brenner BM, editors. Hypertension. Pathophysiology, diagnosis and management. 2nd ed. New York Raven Press 1995. p. 2917-36. 

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. 

At still higher concentrations, dopamine causes a-adrenoceptor-mediated vasoconstriction in most vascular beds and stimulates the heart. Total peripheral resistance may be increased. If the concentration of dopamine reaching the tissue is high enough, vasoconstriction of the renal and mesenteric beds also occurs. The vasoconstrictive action of dopamine is antagonized by a-adrenoceptor blocking agents such as phentol-amine. 

Ultra-short-acting 3-adrenoceptor blocking agent. May also show class III activity. 

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

Esmolol (Brevibloc) is a short-acting intravenously administered Pi-selective adrenoceptor blocking agent. It does not possess membrane-stabilizing activity or sympathomimetic activity. 

Sotalol decreases conduction velocity and prolongs the ERP in the A-V node, an action held in common with other 3i-adrenoceptor blocking agents. 

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... 

The adrenoceptor-blocking agents are described in detail in Chapter 11, although their use in the treatment of hypertension is briefly described here. Drugs of this group are subdivided into a-adrenoceptor antagonists (a-blockers) and (3-adrenoceptor antagonists ((3- blockers). 

E. The first four choices all are associated with erectile dysfunction. Although a-adrenoceptor blocking agents are not approved for the treatment of erectile dysfunction, they have been shown to have some effectiveness. 

Saw palmetto extract is a fairly well tolerated, safe alternative to finasteride for long-term treatment of BPH, although tti-adrenoceptor blocking agents undoubtedly afford more rapid symptom relief. 

Propranolol was the first blocker shown to be effective in hypertension and ischemic heart disease. Propranolol has now been largely replaced by cardioselective blockers such as metoprolol and atenolol. All B-adrenoceptor-blocking agents are useful for lowering blood pressure in mild to moderate hypertension. In severe hypertension, blockers are especially useful in preventing the reflex tachycardia that often results from treatment with direct vasodilators. Beta blockers have been shown to reduce mortality after a myocardial infarction and some also reduce mortality in patients with heart failure they are particularly advantageous for treating hypertension in patients with these conditions (see Chapter 13). 

During the acute phase of thyrotoxicosis, B-adrenoceptor blocking agents without intrinsic sympathomimetic activity are extremely helpful. Propranolol, 20-40 mg orally every 6 hours, will control tachycardia, hypertension, and atrial fibrillation. Propranolol is gradually withdrawn as serum thyroxine levels return to normal. Diltiazem, 90-120 mg three or four times daily, can be used to control tachycardia in patients in whom blockers are contraindicated, eg, those with asthma. Other calcium channel blockers may not be as effective as diltiazem. Adequate nutrition and vitamin supplements are essential. Barbiturates accelerate T4 breakdown (by hepatic enzyme induction) and may be helpful both as sedatives and to lower T4... 

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