22. Histamine, antihistaminic drugs


Histamine is a basic amine that is formed from histidine by histidine decarboxylase. Mast cells, basophils, histamininergic neurons and enterochromaffin cells produce it. Mast cells are especially abundant in the respiratory tract, GI tract and skin.

Mast cells have granules that contain histamine and other compounds. These granules are exocytosed (called degranulation) when the IgE molecules bound to the cell bind to an antigen. This is part of the hypersensitivity type I reaction.

Certain drugs force mast cells to granulate, like tubocurarine, suxamethonium, vancomycin and morphine. These drugs therefore have itching as a side effect due to histamine release.

Enterochromaffin cells in the GI tract produce histamine in response to parasympathetic stimulation (acetylcholine) or gastrin. This causes the parietal cells to produce HCl.

Histamine is a neurotransmitter in the brain. It increases wakefulness, which is why you might feel sleepy after taking histamine antagonists.

Histamine binds to four receptors:

Receptor Response
Histamine 1 receptor (H1) Vasodilation

Smooth muscle contraction (except vascular)


Histamine 2 receptor (H2) Cardiac stimulation

HCl secretion

Histamine 3 receptor (H3) Not so important
Histamine 4 receptor (H4) Definitely not important

If you give histamine intradermally will there be three responses, together called the “triple response of Lewis”: Erythema, wheal (elevated bump), flare (redness in surrounding area). The same response occurs if you get poisoned by stinging nettles.

You’re probably itching right now.

Histamine antagonists

H1 antagonists are divided into first generation and second generation.

First generation H1 antagonists like diphenhydramine, dimenhydrinate, cyclizine, clemastine and promethazine penetrate the blood-brain barrier. They’re mostly used for their CNS effects, like sedation, anti-motion sickness and anti-emetics.

Second generation H1 antagonists like cetirizine, loratadine and fexofenadine don’t penetrate the blood-brain barrier much and are therefore used to treat allergies.

H2 antagonists like cimetidine and famotidine are used to decrease HCl secretion in the stomach, treating heartburn and acid-induced indigestion. They also increase healing of gastric and duodenal ulcers.

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21. Local anesthetics

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23. Pharmacology of eicosanoids. Drugs acting on smooth muscle

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