Antihistamines: H 1- and H 2-Blockers


This chapter focuses on adverse effects and accompanying complications of the H 1 and H 2 antihistamine medication classes. Basic pharmacology and common uses for each drug are outlined. Additional topics include a description of signs and symptoms of toxicity, implications and risks, management and treatment options, and prevention.


anticholinergic toxicity, cimetidine, diphenhydramine, famotidine, H 1 antihistamine, H 2 antihistamine, promethazine


Case Synopsis

A 90-year-old man with a past medical history of multiinfarct dementia presented with hematuria and is found to be confused and agitated in the postanesthesia care unit after cystourethroscopy. The patient received midazolam preoperatively, fentanyl and propofol on induction, and 50 mg of diphenhydramine after an episode of erythema.


This author wishes to acknowledge Drs. Habibi and Riley for contributions to the chapter in the previous edition of this book.

Problem Analysis


The antihistamine drug class can be divided into four separate types based on interaction with four known receptor subtypes (H 1 , H 2 , H 3 , H 4 ). H 1 – and H 2 -receptor antagonists or “blockers” are in fact inverse agonists that shift equilibrium of the receptor-drug complex toward inactivity. Histamine receptors are located at multiple sites, including smooth muscle, exocrine glands, and the central nervous system (CNS). First-generation H 1 antihistamines have additional activity at muscarinic receptors, α-adrenergic receptors, and serotonergic receptors. Primary uses for H 1 antihistamines include treatment of allergic rhinitis, allergic conjunctivitis, and urticaria; prevention of hypersensitivity reactions; treatment of motion sickness; and as a sleep aid.

The H 1 antihistamine class was modified to increase H 1 specificity and to limit adverse effects. Second-generation H 1 antihistamines do not cause anticholinergic symptoms to the same degree as their predecessor and have a limited ability to cross the blood-brain barrier, thus attenuating CNS effects. The second-generation H 1 antihistamines are now the preferred treatment for allergic symptoms.

Histamine-stimulated release of gastric acid is unchanged by H 1 -receptor activity. The absence of this reaction led to the discovery of the H 2 -receptor subtype and the development of H 2 antihistamines. H 2 antihistamines act to prevent histamine release from enterochromaffin cells in the stomach, which halts parietal cell secretion of gastric acid. H 2 antihistamines provide treatment for patients with mild peptic ulcer disease, gastroesophageal reflux disease, and stress ulcer prophylaxis ( Table 84.1 ).

TABLE 84.1

Commonly Encountered Antihistamines

First-Generation H 1 Antihistamines Second-Generation H 1 Antihistamines H 2 Antihistamines


Anticholinergic effects predominate in the first-generation H 1 antihistamines due to their action at muscarinic receptors. Symptoms of anticholinergic activity include mydriasis, CNS disturbances, erythema, hyperpyrexia, and urinary retention. The anticholinergic toxidrome can be recalled by the mnemonic “blind as a bat, mad as a hatter, red as a beet, hot as a hare, dry as a bone.” Mild CNS changes can occur with therapeutic doses leading to sedation, impaired cognition, and hyperexcitability with confusion and combativeness (particularly in pediatric patients). Dystonia has been reported after administration of therapeutic doses of diphenhydramine. CNS effects and anticholinergic effects occur in first-generation H 1 antihistamines to a much greater degree than in second-generation medications.

The severity of symptoms varies with dosage, but toxic thresholds are not well defined by the literature. First-generation H 1 antihistamine overdose is encountered when used in suicide attempts or when used as a recreational drug. These patients may present with agitation or hallucinations followed by seizures, coma, respiratory depression, rhabdomyolysis, and cardiac arrhythmias.

H 2 antihistamine side-effect symptoms include diarrhea, constipation, myalgia, and drowsiness. CNS changes such as delirium and hallucinations have been noted with intravenous administration of H 2 antagonists in geriatric populations. Hypotension may occur with rapid intravenous administration ( Table 84.2 ).

Feb 18, 2019 | Posted by in ANESTHESIA | Comments Off on Antihistamines: H 1- and H 2-Blockers
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