Medical Pharmacology Chapter 21:  Histamine

• Non-Histamine Receptor-Mediated Effects

  • First-generation H₁ receptor blockers cause effects mediated by many other receptor systems.

    • These other effects in the mediated by

      • Muscarinic cholinergic receptors

      • α-adrenergic receptors

      • Serotonergic receptors and

      • Local anesthetic receptor sites.

  • Sedation

    • Sedation is a common side effect of first-generation H₁ antagonists and provided the rationale for these agents to be used has sleep-aids, i.e. hypnotics. 

      • These agents may produce a paradoxical excitement and children and toxic reactions can include stimulation, agitation, or even coma.

      • The newer H₁ antagonists, by contrast, cause minimal or no sedation.

  • Anti-emetic/Antinausea

    • Some first-generation H₁ antagonists prevent motion sickness. 

    • In this application these agent should be used as prophylaxis. 

    • Therefore they should be taken well in advance of the activity which might be expected to induce motion-sickness.  

  • Anti-Parkinsonism 

    • Certain first-generation H₁ antagonists, because of their antimuscarinic properties, turn out to be effective in suppressing Parkinsonian symptoms which are side-effects of some antipsychotic medications. 

    • The antipsychotic drugs involved here tend to be "first-generation" agents which have numerous neurological side effects. 

      • The side effects are much less prevalent with newer antipsychotic drugs, such as olanzapine (Zyprexa) or risperidone (Risperdal).

  • Anticholinergic effects

    • Some first-generation H₁ antagonists have strong antimuscarinic actions (atropine-like effects). 

    • Prominent anticholinergic effects include blurred vision (loss of accommodation) and urinary retention. 

      • Therefore patients who may have benign prostatic hypertrophy may exhibit significant worsening of their clinical state due to antimuscarinic effects. 

        • Probably benign prostatic hypertrophy would be one example of the syndrome for which there would be a relative contraindications for these drugs.

  • α adrenergic blocking effects

    • Some first-generation H₁ antagonists block α-adrenergic receptors.

    • α-adrenergic receptor blockade can cause orthostatic (postural) hypotension.  

  • Serotonergic blockade

    • Some first-generation H₁ antagonists block serotonin receptors

  • Local Anesthetic effects

    • Many first-generation H₁ antagonists are local anesthetics, exhibiting sodium channel blockade [similar in general to that caused by procaine (Novocain) and lidocaine (Xylocaine)].

    • For example, diphenhydramine (Benadryl) and promethazine (Pherergan) are more potent than procaine (Novocain) as a local anesthetic.

1. 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.

2. 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.