Epinephrine antagonists

Among the antianaphylactic drugs, epinephrine (adrenaline) is the essential substance. In the acute treatment of the anaphylaxis in addition to the classical ABC (airway, breathing, circulation) rule for cardiopulmonary resuscitation [26, 27], one can apply the AAC rule (antigen off, adrenaline, cortisone) [18], Other drugs playing a role in the treatment of anaphylaxis include antihistamines (Hi-antagonists). 

Cederbaum, JM and Aghajanian, GK (1976) Noradrenergic neurons of the locus coeruleus inhibition by epinephrine and activation by the alpha-antagonist piperoxane. Brain Res. 112 413-419. 

Figure 3 Putative model for the mechanism by which biogenic amines stimulate CE secretion across the rabbit corneal epithelium. Epn = epinephrine Nep = norepinephrine Tim = Timolol Ser = serotonin Msg = methysergide Dop = dopamine Hal = haloperi-dol (E = (E-adrenoceptor AC = adenylate cyclase. The scheme is consistent with the observation that epithelial responsiveness to serotonin and dopamine can be blocked by their receptor antagonists haloperidol and methysergide, respectively, and by both timolol treatment and sympathectomy. The probable source of serotonin or dopamine is the sympathetic fibers that innervate the cornea. (From Ref. 284.)...

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. 

There is evidence that y-aminobutyric acid A receptors may be modified during SE and become less responsive to endogenous agonists and antagonists. Two phases of GCSE have been identified. During phase I, each seizure produces marked increases in plasma epinephrine, norepinephrine, and steroid concentrations that may cause hypertension, tachycardia, and cardiac arrhythmias. Muscle contractions and hypoxia can cause acidosis, and hypotension, shock, rhabdomyolysis, secondary hyperkalemia, and acute tubular necrosis may ensue. 

P-Sympatholytics are antagonists of norepiphephrine and epinephrine at p-adrenoceptors they lack affinity for a-receptors. 

B. The adrenoceptors that epinephrine acts on to affect heart rate, renin release, bronchiolar tone, and glycogenolysis are (3-receptors. Prazosin is an a-antagonist so would not antagonize epinephrine at those receptors. The radial smooth muscle in the iris has a-receptors that when activated, contract the radial muscle which dilates the pupil. This action is antagonized by prazosin. 

Beta-blockers interact with a large number of other medications. The combination of beta-blockers with calcium antagonists should be avoided, given the risk for hypotension and cardiac arrhythmias. Cimetidine, hydralazine, and alcohol all increase blood levels of beta-blockers, whereas rifampicin decreases their concentrations. Beta-blockers may increase blood levels of phenothiazines and other neuroleptics, clonidine, phen-ytoin, anesthetics, lidocaine, epinephrine, monoamine oxidase inhibitors and other antidepressants, benzodiazepines, and thyroxine. Beta-blockers decrease the effects of insulin and oral hypoglycemic agents. Smoking, oral contraceptives, carbamazepine, and nonsteroidal anti-inflammatory analgesics decrease the effects of beta-blockers (Coffey, 1990). 

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