Prazosin effects

Elliott HL, McLean K, Sumner DJ, Meredith PA, Reid JL. Immediate cardiovascular reponses to oral prazosin-effects of p-blockers. CUn Pharmacol Ther 9 ) 29,303-9. 

OC-Adrenoceptor Blockers. Nonselective a-adrenoceptor blockers (Table 6), such as phentolamine, which block both a - and a2 adrenoceptors, produce vasodilation by antagonizing the effects of endogenous norepinephrine. They also produce severe tachycardia and have been replaced by selective a -adrenoceptor blockers, such as prazosin, terazosin, and doxazosin, which do not usually cause severe tachycardia. 

Prazosin, a selective a -adrenoceptor antagonist, exerts its antihypertensive effect by blocking the vasoconstrictor action of adrenergic neurotransmitter, norepinephrine, at a -adrenoceptors in the vasculature (200,227,228). Prazosin lowers blood pressure without producing a marked reflex tachycardia. It causes arteriolar and venular vasodilation, but a significant side effect is fluid retention. Prazosin increases HDL cholesterol, decreases LDL cholesterol, and does not cause glucose intolerance. 

A large number of diugs interfere with the smooth muscle contraction. These compounds lower blood pressure and are referred to as antihypertensive. In this section, only those coumpounds will be mentioned that have a direct effect on smooth muscle tone. Phenylephrine is an agonist on most smooth muscles and activates ax adrenoceptors. Carbachol is an agonist on some smooth muscles and activates contraction through muscarinic receptors. Blockers of the ax-adrenoceptors such as prazosin and urapidil are competitive inhibitors of the ax-receptor in vascular and bladder smooth muscle. Phenoxybenzamine is an ineversible blocker of ax receptors and phentol-amine blocks ax and a2 receptors. Ca2+ channel blockers such as the dihydropyiidines, phenylalkyla-mines and benzothiazepines lower smooth muscle tone by blocking the L-type calcium channel. 

Antagonism of several characteristic effects of amphetamine and cocaine by the alpha adrenergic receptor antagonist prazosin is a most recent example of noradrenergic mechanisms in the actions of psychomotor stimulants (Tessel and Barrett 1986). We investigated whether or not prazosin may attenuate the disruptive effects of amphetamine on social and aggressive behavior in mice and squirrel monkeys (Miczek, unpublished observations). Pretreatment with prazosin (0.4 mg/kg) attenuated the disruption of attack... 

The decrease in the ability of the aging body to respond to baroreflexive stimuli can result in very serious consequences for elderly patients [115-117]. Because of this decrease in sensitivity and the decreased cardiac output witnessed in elderly patients, they are predisposed to the effects of orthostatic hypotension that can occur when one is taking antihypertensive medication (e.g., prazosin). Indeed, the fact that elderly persons are prone to accidental falls may be due to this change in sensitivity [115-117]. 

Hypertension, or a chronic elevation in blood pressure, is a major risk factor for coronary artery disease congestive heart failure stroke kidney failure and retinopathy. An important cause of hypertension is excessive vascular smooth muscle tone or vasoconstriction. Prazosin, an aradrenergic receptor antagonist, is very effective in management of hypertension. Because oq-receptor stimulation causes vasoconstriction, drugs that block these receptors result in vasodilation and a decrease in blood pressure. 

The major circulating hormones that influence vascular smooth muscle tone are the catecholamines epinephrine and norepinephrine. These hormones are released from the adrenal medulla in response to sympathetic nervous stimulation. In humans, 80% of catecholamine secretion is epinephrine and 20% is norepinephrine. Stimulation of cy-adrenergic receptors causes vasoconstriction. The selective a,-adrenergic receptor antagonist, prazosin, is effective in management of hypertension because it causes arterial and venous smooth muscle to relax. 

Pellejero, T., Monti, J. M., Baglietto, J. et al. (1984). Effects of methoxamine and alpha-adrenoceptor antagonists, prazosin and yohimbine, on the sleep-wake cycle of the rat. Sleep 7, 365-72. 

Prazosin is a selective aradrenergic receptor antagonist that, at therapeutic doses, has little activity at a2-adrenergic receptors and clinically insignificant direct vasodilating activity The drug does not cause the other effects attributed to phentolamine. Most important, it produces less tachycardia than does phentolamine and, therefore, is useful in the treatment of essential hypertension. 

Communication with the profession was at first maintained by continuing (until January 1985) the Adverse Reaction Series leaflets started by CSD, and later by a regularly published bulletin on Current Problems . The first issue of Current Problems in September 1975 led with the adverse oculo-cutaneous effects and sclerosing peritonitis associated with p-adrenergic receptor blocking agents and also included items on loss of consciousness associated with prazosin and on the risks of anti-inflammatory agents and asthma. 

Pharmacokinetics Prazosin is extensively metabolized. The metabolites of prazosin are active. Duration of antihypertensive effect is 10 hours. 

First-dose effect Prazosin, terazosin, doxazosin, alfuzosin, and tamsulosin,... 

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