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Autacoids are endogenous molecules with powerful pharmacologic effects that do not fall into traditional autonomic groups. Histamine and serotonin (5-hydroxytryptamine; 5-HT) are the most important amine autacoids. The ergot alkaloids are a heterogeneous group of drugs (not autacoids) that interact with serotonin receptors, dopamine receptors, and α receptors. They are included in this chapter because of their effects on serotonin receptors and on smooth muscle. Peptide and eicosanoid autacoids are discussed in Chapters 17 and 18. Nitric oxide is discussed in Chapter 19.

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Acid-peptic diseaseDisease of the upper digestive tract caused by acid and pepsin; includes gastroesophageal reflux, erosions, and ulcers
AutacoidsEndogenous substances with complex physiologic and pathophysiologic functions that have potent nonautonomic pharmacologic effects when administered as drugs; commonly understood to include histamine, serotonin, prostaglandins, and vasoactive peptides
CarcinoidA neoplasm of the gastrointestinal tract or bronchi that may secrete serotonin and a variety of peptides
Ergotism ("St. Anthony's fire")Disease caused by excess ingestion of ergot alkaloids; classically an epidemic caused by consumption of grain (eg, in bread) that is contaminated by the ergot fungus
GastrinomaA tumor that produces large amounts of gastrin; associated with hypersecretion of gastric acid and pepsin leading to ulceration
IgE-mediated immediate reactionAn allergic response, for example, hay fever, angioedema, caused by interaction of an antigen with IgE antibodies on mast cells; results in the release of histamine and other mediators of allergy
OxytocicA drug that causes contraction of the uterus
Zollinger-Ellison syndromeSyndrome of hypersecretion of gastric acid and pepsin, often caused by gastrinoma; it is associated with severe acid-peptic ulceration and diarrhea
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Histamine is formed from the amino acidhistidine and is stored in high concentrations in vesicles in mast cells, enterochromaffin cells in the gut, some neurons, and a few other cell types. Histamine is metabolized by the enzymes monoamine oxidase and diamine oxidase. Excess production of histamine in the body (eg, in systemic mastocytosis) can be detected by measurement of its major metabolite, imidazole acetic acid, in the urine. Because it is released from mast cells in response to IgE-mediated (immediate) allergic reactions, this autacoid plays a pathophysiologic role in seasonal rhinitis (hay fever), urticaria, and angioneurotic edema. (The peptide bradykinin also plays an important role in angioneurotic edema, see Chapter 17.) Histamine also plays a physiologic role in the control of acid secretion in the stomach and as a neurotransmitter.

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Receptors and Effects

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Two receptors for histamine, H1 and H2, mediate most of the peripheral actions; 2 others (H3, H4) have also been identified (Table 16–1). The triple response, a classic demonstration of histamine effect, is mediated mainly by H1 and H2 receptors. This response involves a small red spot at the center of an intradermal injection of histamine ...

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