NJC_H2_CHEM_CM_Answers

1 NJC Preliminary Examination 9812/01/17 [Turn over H3 Pharmaceutical Chemistry (9812) 2017 Preliminary Examination 1 (a) (i) Non–Narcotics Paracetamol Aspirin Diflunisal Narcotics Codeine (ii) A narcotic analgesic is a substance that depresses the activity of the central nervous system (CNS) affecting the brain’s capacity to sense pain. (Alternative answer: by binding with pain receptors in the brain and blocking transmission of pain signals between brain cells.) A non-narcotic analgesic act as inhibitor of the cyclo-oxygenase (COX) enzyme. This prevents the formation of prostaglandins that send pain messages to the brain. (iii) Prolonged consumption of aspirin inhibits cyclo -oxygenase, inhibiting the production of stomach lining (gastric mucosa). Hence, exposing the stomach wall and its associated blood supply to attack by strong acid causing ulcers and bleeding respectively. (iv) Any 2 of the following:  Paracetamol is safe for children below age of 12 (but dosage has to be different)  Less irritating sensation than aspirin  Does not cause blood thinning or prevents clot or prolonged bleeding  Used when patient has stomach ulcer  Used when anti–inflammatory action is not required.  As alternative for patients who are allergic to salicylate derivatives (v) Competitive reversible inhibition/inhibitor. With increasing [natural substrate], there is an increased competition by the natural substrate for active site of enzyme, increasing the rate of enzymatic reactions. At high [substrate], the rate of enzymatic reaction with diflunisal is the same as that without application of the drug indicating natural substrates out compete the diflunisal for the active sites of the enzyme.

2 NJC Preliminary Examination 9812/01/17 (vi) The rate of enzymatic reaction with aspirin still increases with increasing [natural substrate], however, the maximum rate is lower than the case of diflunisal. This is because aspirin is a non-competitive irreversible inhibitor of COX enzymes, where the drug is permanently bound to the enzyme blocking the access of the natural substrate reducing the maximum reaction possible. (b) (i) tertiary amine : ionic bonding/ion–dipole interaction/ionic interaction phenolic –OH : hydrogen bonding benzene ring : VDWs forces/Hydrophobic interaction (ii) 6-acetylmorphine is less polar than morphine as one of the polar –OH group is masked as ester. Diamorphine has two polar groups masked as esters making it the least polar among the 3 drugs . Hence, diamorphine is most efficient in crossing the non–polar blood–brain barrier and in greater concentration, followed by 6–acetylmorphine and least for morphine. However, 3–acetylmorphine has greater analgesic effect than diamorphine as the phenolic –OH that i