Administration of H₁ and H₂ Antagonists for Chemoprophylaxis: A Double‐Blind, Placebo‐Controlled Study in Healthy Volunteers

Abstract

A double-blind, placebo-controlled trial was performed to establish the duration of action of antihistamines and their ability to attenuate the adverse affects associated with histamine release. Thirty volunteers were assigned randomly to receive either placebo or a combination of the H1 blocker dimetindene maleate (0.1 mg/kg) and the H2 blocker cimetidine (5 mg/kg). A bolus dose of histamine (450 ng/kg) was given 15 minutes after antihistamine or placebo treatment and repeated after 2, 4, and 6 hours. Cardiovascular variables, plasma histamine levels, cutaneous manifestations, and objective and subjective signs and symptoms associated with histamine release were determined before and after each histamine injection. Although many of the signs of histamine release, including erythema and metallic taste, could be attenuated effectively for 6 hours with antihistamine treatment, the protection against histamine-induced flush and headache diminished after 2 hours. Statistically significant protection against histamine-mediated tachycardia persisted for only 2 hours. Antihistamine treatment significantly reduced the increase in plasma histamine levels after the first histamine injection but did not alter the levels after subsequent histamine injections. The currently recommended administration regimen for prophylaxis with antihistamines is insufficient to prevent histamine-mediated side effects, and additional doses may be required after 4 hours to achieve appropriate chemoprophylaxis.

Premedication with H1 and H2 blocking agents reduces the incidence of postoperative nausea and vomiting

“…may have a specific effect on the H 2 receptors of the stomach, thus reducing the excretion of gastric juice before anaesthetics are given. Prophylaxis with H 1 /H 2 receptor antagonists lessens the amount of histamine release after administration of hypnotics, analgesics and muscle relaxants and also reduces cutaneous reactions and changes in blood pressure [30][31][32]. For example, oral premedication with H 1 and H 2 antagonists prevents the haemodynamic and cutaneous adverse effects caused by mivacurium [33].…”

Pruritic dermatoses: overview of etiology and therapy

“…Maximum benefit often requires the administration of doses higher than those recommended. Doenicke et al 63 found that currently recommended regimens do not adequately prevent the effects of histamine and suggest that additional doses after 4 hours may be needed to achieve an adequate therapeutic response. Flushing is the first symptom to respond to antihistamine therapy.…”

New antihistamines – perspectives in the treatment of some allergic and inflammatory disorders

“…Nowadays, there are no new H2R antagonists intended to treat allergic and inflammatory disorders. In cases of severe or persistent urticaria refractory to treatment with H1R antihistamine alone, H2R antagonists can also be used off-label [9, 36].…”