indication

For the treatment of rhinitis, urticaria, allergy, common cold, asthma and hay fever.

pharmacology

In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H₁-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Chlorpheniramine, is a histamine H1 antagonist (or more correctly, an inverse histamine agonist) of the alkylamine class. It competes with histamine for the normal H₁-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies.

mechanism of action

Chlorpheniramine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.

toxicity

Oral LD50 (rat): 306 mg/kg; Oral LD50 (mice): 130 mg/kg; Oral LD50 (guinea pig): 198 mg/kg [Registry of Toxic Effects of Chemical Substances. Ed. D. Sweet, US Dept. of Health & Human Services: Cincinatti, 2010.] Also a mild reproductive toxin to women of childbearing age.

biotransformation

Primarily hepatic via Cytochrome P450 (CYP450) enzymes.

absorption

Well absorbed in the gastrointestinal tract.

half life

21-27 hours

drug interactions

Donepezil: Possible antagonism of action

Ethotoin: The antihistamine increases the effect of hydantoin

Fosphenytoin: The antihistamine increases the effect of hydantoin

Galantamine: Possible antagonism of action

Mephenytoin: The antihistamine increases the effect of hydantoin

Phenytoin: The antihistamine increases the effect of hydantoin

Rivastigmine: Possible antagonism of action

Tacrine: The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Chlorpheniramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.

Telithromycin: Telithromycin may reduce clearance of Chlorpheniramine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Chlorpheniramine if Telithromycin is initiated, discontinued or dose changed.

Trimethobenzamide: Trimethobenzamide and Chlorpheniramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Triprolidine: Triprolidine and Chlorpheniramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.

Trospium: Trospium and Chlorpheniramine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of chlorpheniramine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of chlorpheniramine if voriconazole is initiated, discontinued or dose changed.