Epinephrine reversal

Top Effects of phentolamine, an a-receptor-blocking drug, on blood pressure in an anesthetized dog. Epinephrine reversal is demonstrated by tracings showing the response to epinephrine before (middle) and after (bottom) phentolamine. All drugs given intravenously. BP, blood pressure HR, heart rate. 

In contrast to phenoxybenzamine, phentolamine [fen TOLE a meen] produces a competitive block of ai and a2 receptors. The drug s action lasts for approximately 4 hours after a single administration. Like phenoxybenzamine, it produces postural hypotension and causes epinephrine reversal. Phentolamine had been used in the diagnosis of pheochromocytoma and in other clinical situations associated with excess release of catecholamines. Phentolamine-induced reflex cardiac stimulation and tachycardia are mediated by the baroreceptor reflex and by blocking the a2 receptors of the cardiac sympathetic nerves. The drug can also trigger arrhythmias and anginal pain and is contraindicated in patients with decreased coronary perfusion. 

Folts JD, Rowe GG (1988) Epinephrine reverses aspirin inhibition of in vivo platelet thrombus formation in stenosed dog coronary arteries. Thromb Res 50 507-516... 

Rao GHR, Escolar G, White JG. Epinephrine reverses the inhibitory influence of aspirin on vessel-wall interaction. Throm Res 1986 47 625-637... 

Of the drugs listed, only isoproterenol causes a decrease in mean blood pressure, because it activates beta receptors and has no effect on alpha receptors. This permits identification of drug 3 as isoproterenol. Prazosin is an alpha blocker, so one can anticipate that this drug would antagonize any increases in blood pressure that result from activation of (Xj receptors in the vasculature. Epinephrine (high dose), norepinephrine, and tyramine all exert pressor effects via activation of (Xj receptors. However, only epinephrine is active on P2 receptors, and this action would be revealed by vasodilation and a reversal of its pressor effects following treatment with an alpha blocker— epinephrine reversal. Thus, drug 4 can be identified as epinephrine. 

Molindone (50 to 75 mg/day) is indicated in the management of the manifestations of psychotic disorders. Molindone is strncturally nnrelated to the phenothiazines, butyrophenones, or thioxanthenes, but it resembles the piperazine phenothiazines in its clinical action. It causes sedation, possesses anticholinergic properties and, similar to flnphenazine, produces movement disorders. Molindone is metabolized, and the metabolites are excreted in the nrine. It lowers the seizure threshold and may cause seizures in patients with epilepsy and other seizure disorders. Concomitant nse with sympathomimetics, including epinephrine, phenylephrine, phenylpropanolamine, and ephedrine (often fonnd in nasal sprays), or appetite suppressants may decrease their stimulatory and pressor effects. Becanse of its alpha-blocking potential, molindone may canse epinephrine reversal—a hypotensive response to epinephrine. 

Concomitant use of perphenazine with sympathomimet-ics, including epinephrine, phenylephrine, phenylpropanolamine, and ephedrine (often found in nasal sprays), and with appetite suppressants may decrease their stimulatory and pressor effects. Phenothiazines can cause epinephrine reversal and a hypotensive response when epinephrine is used for its pressor effects. 

Phenoxybenzamine is a noncompetitive alpha-adrenergic-receptor blocker, and its action cannot be nuUifled by increasing the amount of agoinst, or agoinsts. It causes epinephrine reversal in that the administration of epinephrine after pretreatment with phenoxybenzamine elicits vasodilation, and, conversely, phenoxybenzamine reverses epinephrine-mediated vasoconstriction to vasodilation (see also Figure 37). 

Is the epinephrine reversal" phenomenon seen with norepinephrine or other cardios-timulatory drugs, such as isoproterenol ... 

This phenomenon is known as "epinephrine reversal. Epinephrine, which was administered just prior to administration of prazocin, acts as an agonist at both p2 (vasodilatory) and (vasoconstrictor) receptors. Administration of prazosin blocks the vasoconstrictor action of the a, receptors, leaving only the vasodilator actions of the p2 receptor, resulting in a rapid and profound lowering of blood pressure. 

Epinephrine reversal Use of blocker to reverse hypertension to hypotension in a patient receiving too much epinephrine... 

Epinephrine reversal Conversion of the pressor response (typical of large doses of epinephrine) to a blood pressure-lowering effect caused by alpha blockers... 

Epinephrine reversal is a predictable result of the use of this agonist in a patient who has received an alpha-blocker. The term refers to a reversal in the blood pressure effect of moderate to large doses of epinephrine, from a pressor response (mediated by alpha-receptors) to a depressor response (mediated by pj-receptors) (Figure 10-2). The effect is not observed with phenylephrine or norepinephrine because these drugs lack p effects. 

Epinephrine reversal is occasionally seen as an unexpected (but predictable) effect of drugs for which alpha blockade is an adverse effect (eg, some phenothiazine tranquilizers, antihistamines). 

Note that the original workup of the patient showed highly elevated metanephrine but lower than normal normetanephrine. This suggests that the tumor produces almost pure epinephrine and little or no norepinephrine (recall the metabolites of epinephrine and norepinephrine from Chapter 6). A patient with this type of tumor may have a dramatic epinephrine reversal response to any alpha-blocker, plunging the blood pressure to shock levels. This is especially true if the blood volume is low. Although most pheochromocytomas produce a mixture of norepinephrine and epinephrine, cases like the one described have been reported in the literature. The answer is (C). 

Although it does not act at any histamine receptor, epinephrine reverses many effects of histamine. Epinephrine is a (A) Competitive inhibitor of histamine... 

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