Medical Pharmacology Chapter 21: Histamine
Clinical Uses: H1 Histamine Receptor Blockers
The pharmacological objective in the use of these medications is to treat or prevent symptoms of allergic reaction.
H1 histamine receptor blockers are drugs of choice to treat allergic rhinitis and urticaria.
In both cases, histamine is the primary mediator of the symptoms
By contrast, in asthma their multiple mediators and H1 histamine receptor blockers are ineffective.
Angioedema (hives) may be initiated by histamine but are maintained by bradykinins.
In this clinical setting H1 histamine receptor blockers are also ineffective.
For atopic dermatitis, diphenhydramine which is a H1 histamine receptor blocker proves effective in control of itching and for sedation.
For allergic conditions, an example being hay fever, the H1 histamine receptor blockers are effective for symptomatic relief.
The goal is to minimize sedating effects while retaining beneficial symptomatic relief.
The Second-generation H1 histamine receptor blockers, for example terfenadine (Seldane) or astemizole (Hismanal) are beneficial because they exhibit minimal sedation while being effective in management of allergic rhinitis and chronic urticaria.
At present, these medications tend to be more expensive than first-generation histamine receptor H1 antagonists.
Scopolamine and certain first-generation H1 blockers are among the most effective drugs for motion sickness prevention
Diphenhydramine and promethazine are the H1 blockers with the greatest effectiveness
Cyclizine (Marezine) and meclizine are also effective agents and are less sedating than those above.
Nausea and Vomiting (Pregnancy)
H1 blockers are not recommended for use in management of nausea and vomiting associate with pregnancy because:
Difficulty in assessment of possible birth defects associated with certain H1 (benedictin) antagonists and known teratogenic effects of others (e.g., doxylamine) in animal models.
Uncommon toxic effects following systemic demonstration:
Excessive excitation and convulsions in children
Orthostatic (postural) hypotension
Drug allergy is relatively common, following topical use of H1 antagonists
First-generation overdosage: similar to atropine overdosage
Second-generation overdosage: may induce cardiac arrhythmias
Second-generation H1 blockers:
Toxicity follows combination of terfenadine or astemizole combined with ketoconazole (Nizoral), itraconazole (Sporanox), or macrolide antibiotics (e.g.,erythromycin) because-
Q-T (ECG) prolongation
Ventricular arrhythmias which may be potentially fatal.
Terfenadine (Seldane)/astemizole (Hismanal) are contraindicated in patients taking ketoconazole (Nizoral), itraconazole (Sporanox), macrolide antibiotics, and patients with diminished liver function.
Patients taking ketoconazole (Nizoral), itraconazole (Sporanox), macrolide antibiotics, and patients with diminished
Fexofenadine (Allegra), a metabolite of terfenadine (Seldane), appears safer.
Burkhalter, A, Julius, D.J. and Katzung, B. Histamine, Serotonin and the Ergot Alkaloids (Section IV. Drugs with Important Actions on Smooth Muscle), in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 261-286.
Friedman, L. S. and Peterson, W.L. Peptic Ulcer and Related Disorders In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., and Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp. 1597-1616.