Adrenoceptor antagonists/blockers

Prolonged exposure of -adrenoceptor agonists down-regulates -adrenoceptors, ie, their number decreases and they become less responsive. On the other hand, prolonged exposure to -adrenoceptor antagonists (those without ISA) upregulates -adrenoceptors, ie, their numbers increase and they become more responsive. Therefore, patients on -adrenoceptor blocker therapy should be withdrawn from this medication gradually (40). 

In the treatment of hypertension, ACE inhibitors are as effective as diuretics, (3-adrenoceptor antagonists, or calcium channel blockers in lowering blood pressure. However, increased survival rates have only been demonstrated for diuretics and (3-adrenoceptor antagonists. ACE inhibitors are approved for monotherapy as well as for combinational regimes. ACE inhibitors are the dtugs of choice for the treatment of hypertension with renal diseases, particularly diabetic nephropathy, because they prevent the progression of renal failure and improve proteinuria more efficiently than the other diugs. 

The risk of atrial flutter is a 2 1 transmission to the ventricles generating a high ventricular rate. The therapeutic goal is to reduce transmission to 3 1 or 4 1 by administration of either (3-adrenoceptor antagonists, Ca2+ channel blockers or amiodarone. Quinidine must not be used in this arrhythmia, since it accelerates AV-conduction due to its vagolytic effect. 

Mydriasis is induced by ai-adrenoceptor-mediated contraction of the radial pupillary dilator muscle of the iris. Furthermore, activation of this receptor subtype induces an increased outflow of humor from the eye while /i-adrenoceptor stimulation mediate an enhanced humor production which contributes to an increased intraocular pressure. /3-Adrenoceptor antagonists (/3-blocker) can be used in the treatment of glaucoma. 

O -Adrenoceptor antagonists (o -blockers) are competitive inhibitors at the level of Q -adrenoceptors. These receptors are found in many organs and tissues, but their predominant functional importance is to mediate the vasoconstrictor effects of endogenous catecholamines (noradrenaline, adrenaline) released from the sympathetic nerve endings. Conversely, Q -adrenoceptor antagonism by means of an a-blocker will inhibit this constrictor activity and hence cause vasodilatation. This vasodilator effect occurs in both resistance vessels (arterioles) and capacitance vessels (veins), since a-adrenoceptors are present in both types of vascular structures. Accordingly, both cardiac afterload and preload will be lowered, in particular when elevated. 

Adrenoceptors of the /3-subtype are important mediators of the sympathetic activation of the heart, kidney, and bronchi. /3-Adrenoceptors are also found in other organs and tissues such as blood vessels and the central nervous system. Accordingly, /3-adrenoceptor antagonists or jS-blockers inhibit the stimulating influence of the endogenous catecholamines (noradrenaline, adrenaline) on the various organs and tissues which are subject to sympathetic innervation. In cardiovascular medicine the /3-blockers are used in particular to blunt the sympathetic activation of the heart and kidneys. These effects are mediated by the /3i-subtype of the /3-adrenoceptors. The currently used /3-blockers are all competitive antagonists of the /3i-adrenoceptor, which is the basis of their therapeutic application. 

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). 

Traditional long-term anti-ischaemic triple therapy for coronary artery disease consists of a long-acting nitrate, p-adrenoceptor antagonist and a calcium-entry blocker. Most of these agents are also used for the treatment of hypertension. 

Volatile anaesthetics, calcium channel-entry blockers, and some anti-arrhythmic drugs may potentiate the negative inotropic effect of the 3-adrenoceptor antagonists. Concomitant digoxin therapy may cause AV dissociation. Potentiation of the hypoglycaemic effects of insulin and oral antidiabetic drugs may occur. 

Concomitant use with sympathomimetic drugs, p-adrenoceptor antagonists, calcium channel-entry blockers and other cardioactive drugs may result in bradyarrhythmias, bigemini, or tachyarrhythmias. Cardiac rhythm should be closely monitored and drug dosages carefully adjusted. Digoxin is mainly excreted by the kidneys and plasma levels should be closely monitored in patients with acute renal failure and in those whose renal function is compromised. 

Combined therapy using calcium channel blockers with p-adrenoceptor antagonists is increasingly common, and is probably safest with the dihydropyridines. Synergy occurs that can lead to marked interference with... 

Labetalol is a reversible adrenoceptor antagonist available as a racemic mixture of two pairs of chiral isomers (the molecule has two centers of asymmetry). The (S,S)- and (R,S)-isomers are nearly inactive, (S,R)- is a potent blocker, and the (R,R)-isomer is a potent 13 blocker. Labetalol s affinity for receptors is less than that of phentolamine, but labetalol is -selective. Its 13-blocking potency is somewhat lower than that of propranolol. Hypotension induced by labetalol is accompanied by less tachycardia than occurs with phentolamine and similar a blockers. 

Antihypertensive Agents. Hypertension (high blood pressure) is a significant risk factor for cardiovascular diseases such as angina heart attacks, and strokes. /(-Adrenoceptor (adrenergic nervous system receptors of the /(-type) antagonists (/(-blockers), calcium channel blockers, angiotensinconverting enzyme (ACE) inhibitors, and potassium channel activators... 

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