H1-Receptor Antagonists Clinical Problems

Paradoxical excitation in children topical use leading to allergy antimuscarinic & CNS effects (min in 2^nd gen)

Astemizole & terfenadine: potentially fatal, cardia tachyarrhythmias!! (out of market)

• 1^st generation Vs 2^nd generation antihistamines: 2^nd gen do not penetrate CNS very well & mainly differ from 1^st gen by producing much less sedation. Currently available 2nd gen have very little antimuscarinic activity. None have partial agonist activity.

• Both H1 & H2 receptors mediate vasodilation. At high doses of histamines, both Receptors are activated, & full antagonism requires use of a combination of H1 & H2 antagonists.

• H1 causes bronchoconstriction; H2 causes gastric acid secreation; H3 causes inhibition of NE release. Note: decreased force of ventricular contraction & stimulation of basophil degranulation are not actions of histamines.

• Sedating actions of 1^st ngeeration H1 antagonists can be caused by blockade of CNS muscarinic Receptors & H1 Receptors.

Category: Pharmacology Notes