Drugs undergoing ACETYLATION include the following EXCEPT: (AIIMS Nov 2011)
(Ref. Harrison's Principles of Internal Medicine 16th Edition pg. 20)
a. N-acetylation is catalyzed by hepatic N-acetyl transferase (NAT), which actually represents the activity of two genes, NAT-1 and NAT-2. Both enzymes transfer an acetyl group from acetyl coenzyme A to the drug; NAT-1 activity is generally constant, while polymorphisms in NAT-2 result in individual differences in the rate at which drugs are acetylated and thus define “rapid acetylators” and “slow acetylators.”
b. Slow acetylators make up about 50% of European- and African-derived populations but are less common among Asians. Indians are slow acetylators; therefore peripheral neuropathy is more common while people of western decent have hepatitis (rapid acetylators).
c. Slow acetylators have an increased incidence of the drug-induced lupus syndrome during procainamide and hydralazine therapy and of hepatitis with isoniazid.
d. Induction of CYPs (e.g., by rifampin) also increases the risk of isoniazid-related hepatitis, likely reflecting generation of reactive metabolites of acetylhydrazine, itself an Isoniazid metabolite.
Metoclopramide is both an antiemetic (that is, it treats nausea and vomiting through an effect within the central nervous system) and a prokinetic. Metoclopramide improves motility in the esophagus and stomach.
a. It is a cholinergic drug that also has ability to block dopamine receptors (D2 blocker).
b. Possible routes of biotransformation are acetylation or deamination followed by oxidation or reduction.
c. Over time, metoclopramide may decrease in its effectiveness as the user develops a tolerance to the drug. And unlike the other prokinetic drugs, metoclopramide is absorbed into the fluid surrounding the brain.
d. Because of this characteristic, metoclopramide can cause undesirable and sometimes alarming neurological side effects such as restlessness and drowsiness.
e. It is the drug of choice for Mendelson’s syndrome (aspiration pneumonitis).