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A 35-year-old man visits his family practitioner with a complaint of red, raised, itchy wheals on his arms and legs. Two days earlier, he had eaten a spicy meal at a restaurant he had not previously visited. The following morning, he woke up with the palms of his hands and the soles of his feet red and itchy. During the day, similar raised, itchy lesions appeared on his arms and legs, and some are now appearing on his trunk. He reports a similar, milder episode 2 years ago, from which he recovered without treatment. Physical examination reveals no respiratory symptoms and no evidence of pharyngeal edema. The practitioner makes a diagnosis of urticaria (hives) caused by food allergy and suggests that the patient take an over-the-counter antihistamine. The following day the patient calls saying that the antihistamine has reduced the itching slightly, but the wheals are still present and new ones are appearing. What other therapeutic measures are appropriate?

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It has long been known that many tissues contain substances that, when released by various stimuli, cause physiologic effects such as reddening of the skin, pain or itching, and bronchospasm. Later, it was discovered that many of these substances are also present in nervous tissue and have multiple functions. Histamine and serotonin (5-hydroxytryptamine, 5-HT) are biologically active amines that function as neurotransmitters and are found in non-neural tissues, have complex physiologic and pathologic effects through multiple receptor subtypes, and are often released locally. Together with endogenous peptides (see Chapter 17), prostaglandins and leukotrienes (see Chapter 18), and cytokines (see Chapter 55), they constitute the autacoid group of drugs.

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Because of their broad and largely undesirable peripheral effects, neither histamine nor serotonin has any clinical application in the treatment of disease. However, compounds that selectively activate certain receptor subtypes or selectively antagonize the actions of these amines are of considerable clinical usefulness. This chapter therefore emphasizes the basic pharmacology of the agonist amines and the clinical pharmacology of the more selective agonist and antagonist drugs. The ergot alkaloids, compounds with partial agonist activity at serotonin and several other receptors, are discussed at the end of the chapter.

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Histamine was synthesized in 1907 and later isolated from mammalian tissues. Early hypotheses concerning the possible physiologic roles of tissue histamine were based on similarities between the effects of intravenously administered histamine and the symptoms of anaphylactic shock and tissue injury. Marked species variation is observed, but in humans histamine is an important mediator of immediate allergic (such as urticaria) and inflammatory reactions, although it plays only a modest role in anaphylaxis. Histamine plays an important role in gastric acid secretion (see Chapter 62) and functions as a neurotransmitter and neuromodulator (see Chapters 6 and 21). Newer evidence indicates that histamine also plays a role in immune functions and chemotaxis of white blood cells.

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Basic Pharmacology of Histamine

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Chemistry & ...

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