Chloropheniramine

Absorption

Well absorbed in the gastrointestinal tract.

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.

Chemical properties

BP

The Uses of Chloropheniramine

Chlorpheniramine is a drug in the class of first-generation antihistamines, used to help alleviate symptoms of allergic reactions potentiated by histamine release. Though it is included in many multisymptom over-the-counter cold relief medications, the Food and Drug Administration (FDA) issued a safety alert in March 2011 detailing some risks associated with these medications. The safety alert also indicated that increased enforcement of FDA laws governing the marketing of these drugs would occur, as many of the products had not been approved in their current formulations for safety, effectiveness, and quality.
Chlorpheniramine is commonly used in small-animal veterinary medicine for its antihistaminic/antipruritic effects, especially for the treatment of pruritus in cats, and occasionally as a mild sedative.

Indications

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

Background

A histamine H1 antagonist used in allergic reactions, hay fever, rhinitis, urticaria, and asthma. It has also been used in veterinary applications. One of the most widely used of the classical antihistaminics, it generally causes less drowsiness and sedation than promethazine.

Definition

ChEBI: Chlorphenamine is a tertiary amino compound that is propylamine which is substituted at position 3 by a pyridin-2-yl group and a p-chlorophenyl group and in which the hydrogens attached to the nitrogen are replaced by methyl groups. A histamine H1 antagonist, it is used to relieve the symptoms of hay fever, rhinitis, urticaria, and asthma. It has a role as a H1-receptor antagonist, an antipruritic drug, a histamine antagonist, a serotonin uptake inhibitor, an antidepressant and an anti-allergic agent. It is a tertiary amino compound, a member of monochlorobenzenes and a member of pyridines.

Pharmacokinetics

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.

Environmental Fate

Toxicity of antihistamines is usually related to their anticholinergic effects and may include loss of appetite, nausea, vomiting, diarrhea or constipation, and other GI effects, as well as dizziness, tinnitus, lassitude, incoordination, fatigue, blurred vision, diplopia, euphoria, nervousness, insomnia, and tremors. Acetylcholine is competitively blocked at muscarinic receptors, resulting in symptoms of anticholinergic poisoning. Concurrent use of alcohol, tricyclic antidepressants, monoamine oxidase inhibitors, or other central nervous system (CNS) depressants along with antihistamines may exaggerate and extend the anticholinergic and CNS depressant effects of antihistamines; concurrent use is not recommended.
Products that were marketed prior to the FDA safety alert but not approved by the FDA included multisymptom cold medications comprised of drug combinations of chlorpheniramine with decongestants, antitussives, and analgesics. Risks associated with the use of these products included improper use in children and infants, potentially risky combination of ingredients, and patients receiving too much or too little medication because of problems with the way some ‘extendedrelease’ products were made. Newborn and premature infants are even more prone to anticholinergic side effects and an increased susceptibility toward convulsions; thus, this drug is not recommended at all in this age group. Geriatric patients are also more prone to anticholinergic effects, and a paradoxical reaction characterized by hyperexcitability may occur in some children taking antihistamines. Overdosage may also produce central excitation resulting in convulsions.

Metabolism

Primarily hepatic via Cytochrome P450 (CYP450) enzymes.