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Chapter 16: Histamine, Serotonin, Drugs Used in Obesity, Ergot Alkaloids, & Other Drugs Used in Migraine

INTRODUCTION

Autacoids are endogenous molecules that do not fall into traditional autonomic groups. They do not act on cholinoceptors or adrenoceptors but have powerful pharmacologic effects on smooth muscle and other tissues. Histamine and serotonin (5-hydroxytryptamine; 5-HT) are the most important amine autacoids. The drugs used in obesity do not have significant smooth muscle effects but have some properties in common with the histamine and serotonin groups. 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. Several drugs used only for migraine headache target the calcitonin gene-related peptide receptor. Other peptide and eicosanoid autacoids are discussed in Chapters 17 and 18. Nitric oxide is discussed in Chapter 19.

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High-Yield Terms to Learn
Acid-peptic disease Disease of the upper digestive tract caused by acid and pepsin; includes gastroesophageal reflux, erosions, and ulcers
Autacoids Endogenous 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
Carcinoid A 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
Gastrinoma A tumor that produces large amounts of gastrin; associated with hypersecretion of gastric acid and pepsin leading to ulceration
IgE-mediated immediate reaction An allergic response, for example, hay fever or angioedema, caused by interaction of an antigen with IgE antibodies on mast cells; results in the release of histamine and other mediators of allergy
Oxytocic A drug that causes contraction of the uterus
Zollinger-Ellison syndrome Syndrome of hypersecretion of gastric acid and pepsin, often caused by gastrinoma; it is associated with severe acid-peptic ulceration and diarrhea

HISTAMINE

Histamine is synthesized from the amino acid histidine 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. Fish that has been stored improperly generates high concentrations of histamine; consumption ...

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