Module 17

Question 1

From the structure of terfenadine, what would you expect to be the major metabolic pathways? What are the major metabolic pathways? What structure is responsible for most of the antihistaminic effects of terfenadine? What is the life-threatening adverse reaction that has been associated with terfenadine, and what molecule is responsible for this reaction? How might this toxicity be avoided?

Answer 1

the alcohol could be glucuronidated or sulfated, the aromatic rings could be oxidized, the alkyl groups in the saturated ring could be oxidized, most likely next to the nitrogen leading to a lactam, the nitrogen could be oxidized, N-dealkylation of the nitrogen could occur, the alkyl groups could get oxidized, oxidation of the alcohol could occur and it could also be glucuronidated or sulfated, the aromatic ring could be oxidized, and the methyl groups could be oxidized, first to an alcohol, then aldehyde, and finally a carboxylic acid

Question 2

Why do many “cold” remedies contain antihistamines?

Answer 2

• Unlike allergies, the runny nose associated with a cold does not involve histamine; therefore, antihistamines are not effective at stopping a runny nose associated with a viral upper respiratory infection.
  
  • The older ones such as benadryl and gravol are sedating, which can help patients with a cold sleep. Dextramethorphan is not an effective cough suppressant. Basically, over the counter cold remedies are worthless. The Canadian Society of Allergy and Clinical Immunology has recommended that the older sedating antihistamines should be “behind the counter”. They are associated with significant side-effects including torsades-de-pointes, sedation leading to auto accidents, fatal overdoses in infants, etc.