Histamine receptor antagonists smooth muscle effects

The answer is e. (Hardman, p 587. Katzung, p 270.) Chlorpheniramine is a competitive Hi-re cep tor antagonist that inhibits most responses of smooth muscle to histamine Hrreceptor antagonists have negligible effects on II2 or II3 receptors... 

Dolasetron and granisetron are 5-HT3 antagonists. Sumatriptan is a 5-HT,p agonist. Ranitidine is a histamine antagonist but blocks the H, receptor in the stomach and the heart, not H, receptors in smooth muscle. Epinephrine has a physiologic antagonist action that reverses histamine s effects on smooth muscle. The answer is (B). 

In medicine and pediatrics, the Hi antagonists are most commonly used for their effects outside the CNS. Outside the CNS they act by blocking the Hi receptors, leading to the inhibition of the following effects of histamine smooth muscle contraction vasoconstriction and, to a lesser degree, the vasodilator effects on en-... 

Phentolamine is a potent competitive antagonist at both K and k2 receptors (Table 10-1). Phentolamine reduces peripheral resistance through blockade of K receptors and possibly k2 receptors on vascular smooth muscle. Its cardiac stimulation is due to antagonism of presynaptic k2 receptors (leading to enhanced release of norepinephrine from sympathetic nerves) and sympathetic activation from baroreflex mechanisms. Phentolamine also has minor inhibitory effects at serotonin receptors and agonist effects at muscarinic and Hi and H2 histamine receptors. Phentolamine s principal adverse effects are related to cardiac stimulation, which may cause severe tachycardia, arrhythmias, and myocardial ischemia. Phentolamine has been used in the treatment of pheochromocytoma. Unfortunately oral and intravenous formulations of phentolamine are no longer consistently available in the United States. 

The effects of histamine released in the body can be reduced in several ways. Physiologic antagonists, especially epinephrine, have smooth muscle actions opposite to those of histamine, but they act at different receptors. This is important clinically because injection of epinephrine can be lifesaving in systemic anaphylaxis and in other conditions in which massive release of histamine—and other mediators— occurs. 

Hi receptor antagonists block the actions of histamine by reversible competitive antagonism at the Hi receptor. They have negligible potency at the H2 receptor and little at the H3 receptor. For example, histamine-induced contraction of bronchiolar or gastrointestinal smooth muscle can be completely blocked by these agents, but the effects on gastric acid secretion and the heart are unmodified. 

Another proposed mechanism is the inhibition of cell surface receptors for adenosine. These receptors modulate adenylyl cyclase activity, and adenosine has been shown to cause contraction of isolated airway smooth muscle and to provoke histamine release from airway mast cells. These effects are antagonized by theophylline, which blocks cell surface adenosine receptors. It has also been shown, however, that xanthine derivatives devoid of adenosine-antagonistic properties (eg, enprofylline) may be more potent than theophylline in inhibiting bronchoconstriction in asthmatic subjects. 

Lidocaine hydrochloride is a local anesthetic/vasopressor preparation. Lidocaine stabilizes neuronal membranes by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action. Epinephrine stimulates both alpha and beta receptors within sympathetic nervous system relaxes smooth muscle of bronchi and iris and is an antagonist of histamine. They are indicated for production of local or regional anesthesia by infiltration techniques such as percutaneous injection, by peripheral nerve block techniques such as brachial plexus and intercostals, and by central neural techniques such as lumbar and caudal epidural blocks. 

Hj and Hj receptors Once released, histamine can exert local or widespread effects on smooth muscles and glands. It contracts many smooth muscles, such as those of the bronchi and gut, but markedly relaxes others, including those in small blood vessels. Histamine also is a potent stimulus of gastric acid secretion see above). Other, less prominent effects include formation of edema and stimulation of sensory nerve endings. Bronchoconstriction and contraction of the gut are mediated by Hj receptors. Gastric secretion results from the activation of Hj receptors and, accordingly, can be inhibited by Hj-receptor antagonists see Chapter 36). 

SMOOTH MUSCLE Within the vascular tree, the Hj antagonists inhibit both the vasoconstrictor effects of histamine and, to a degree, the more rapid vasodilator effects that are mediated by activation of H, receptors on endothehal cells (synthesis/release of NO and other mediators). 

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