Which drug is not metabolized by acetylation
**Core Concept**
Acetylation is a phase II metabolic reaction that involves the conjugation of an acetyl group to a substrate, usually increasing its water solubility and facilitating its excretion. This process is primarily mediated by the enzyme N-acetyltransferase (NAT), which exists in two forms: NAT1 and NAT2.
**Why the Correct Answer is Right**
The correct answer is a drug that is not metabolized by acetylation, meaning it does not require the action of N-acetyltransferase to be inactivated or excreted. This is in contrast to drugs like isoniazid, hydralazine, and procainamide, which are all substrates for NAT2 and undergo rapid acetylation.
**Why Each Wrong Option is Incorrect**
**Option A:** Isoniazid is a well-known substrate for acetylation, and its metabolism by NAT2 is a crucial factor in determining its efficacy and toxicity.
**Option B:** Hydralazine is another drug that undergoes rapid acetylation, and its metabolites are excreted in the urine.
**Option C:** Procainamide is also a substrate for acetylation, and its acetylated metabolite is responsible for its antiarrhythmic effects.
**Clinical Pearl / High-Yield Fact**
Drugs that are metabolized by acetylation can exhibit genetic polymorphism, leading to variations in metabolism and clinical response. This is particularly relevant for isoniazid, where slow acetylators are at increased risk of toxicity.
**Correct Answer: D.**