Cardiovascular system beta-blocker effects

Systemic beta-blockers are used extensively far the treatment of hypertension and other cardiovascular disorders. Of the available oral beta-blockers, atenolol, metoprolol, nadolol, pindolol, propranolol, and timolol have been documented to produce a dose-dependent reduction in lOP. The ocular hypotensive effect associated with systemically administered beta-blockers can be compared with that achieved with topically applied beta-blockers such as timolol. Although specific studies have not been conducted with most of the remaining systemic beta-blockers, these agents might also be expected to reduce lOP at clinically useful doses. 

Geriatric Considerations - Summary Systemic absorption of ophthalmic drugs may occur and cause adverse effects in older adults. Since betaxolol is beta-selective, cardiovascular, respiratory and CNS adverse effects occur less frequently than with beta-nonselective topical opthalmics. These effects may still occur therefore close monitoring for systemic side effects is warranted. Betaxolol maybe less effective than the nonselective topical beta-blockers with an average lOP reduction of 18%-26%. Tachyphylaxis may occur after long-term therapy. 

NICE (2006) also recommends that beta-blockers are not used as an initial therapy for hypertension since they have been shown to be less effective at reducing the risk of a major cardiovascular system event, in particular stroke. 

The respiratory and cardiovascular adverse effects of topical therapy with timolol or betaxolol have been studied in a randomized, controlled trial in 40 elderly patients with glaucoma (83). Five of the 20 allocated to timolol discontinued treatment for respiratory reasons, compared with three of the 20 patients allocated to betaxolol There were no significant differences in mean values of spirometry, pulse, or blood pressure between the groups. This study confirms that beta-blockers administered as eye-drops can reach the systemic circulation and that serious adverse respiratory events can occur in elderly people, even if they are screened before treatment for cardiac and respiratory disease. These events can occur using either the selective betaxolol agent or the non-selective timolol. 

The primary clinical effects observed in beta blocker toxicity are cardiovascular in nature. Direct cardiac effects include bradycardia (sinus, atrioventricular node, and ventricular), all degrees of atrioventricular block, bundle branch blocks, and asystole. Ventricular arrhythmias may occur secondary to bradycardia. Torsades de pointes has been associated with chronic toxicity from sotalol. Hypotension occurs and is due to decreased cardiac output and/or vasodilation. Central nervous system effects of these drugs including lethargy, coma, and seizures are secondary to the cardiovascular toxicities. Seizures and coma may be secondary to hypoglycemia. Bronchospasm can occur secondary to beta-2 blockade. Hypoglycemia and hyperkalemia can occur. 

Oral decongestants should also be avoided by patients taking beta-blockers, as sympathomimetics stimulate both the alpha-adrenoceptors of the cardiovascular system to produce vasoconstriction and the beta-adrenoceptors to produce vasodilatation and stimulation of the heart. The overall effect is a slight increase in both blood pressure and heart rate. If the beta-receptors are blocked, unopposed alpha-adrenoceptor-mediated vasoconstriction can lead to a rise in blood pressure. 

Adrenaline (epinephrine) stimulates alpha- and beta-receptors of the cardiovascular system, the former results in vasoconstriction (mainly alphaj) and the latter in both vasodilatation (mainly beta2) and stimulation of the heart (mainly betaj). The net result is usually a modest increase in heart rate and a small rise in blood pressure. However, if the heta-reeeptors are blocked by a non-selective beta blocker, such as propranolol or nadolol (see Table 22.1 , (p.833) for a list), the unopposed alpha vasoeonstrietion causes a marked rise in blood pressure, followed by reflex bradyeardia. Cardioselective beta blockers such as atenolol and metoprolol, whieh are more selective for betaj receptors, do not prevent the vasodilator aetion of adrenaline at beta2 receptors to the same extent, and therefore the effect of any interaction is relatively small. Consequently, adrenaline has been used to assess the degree of beta blockade produced by propranolol and other beta blockers.Phenylephrine is largely an alpha stimulator, therefore beta blockers should have a minimal effect on its action. 

The normal additive hypotensive effects of these drugs result from the two acting in concert at different but complementary sites in the cardiovascular system. Just why antagonism sometimes occurs is unexplained. The hypertensive rebound following elonidine withdrawal is thought to be due to an increase in the levels of circulating catecholamines. With the beta (vasodilator) effects blocked by a beta blocker, the alpha (vasoconstrictor) effects of the catecholamines are unopposed and the hypertension is further exaggerated. 

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