Disulfiram mainly inhibits the activity of which of the following enzymes?

Appeared in: DSSSB 12 August 2024

Explanation

Disulfiram is a cornerstone of aversion therapy for alcohol use disorder.
Its therapeutic effect comes from irreversibly inhibiting the hepatic enzyme aldehyde dehydrogenase (ALDH).
This inhibition blocks the metabolic breakdown of acetaldehyde, a toxic intermediate of alcohol metabolism.
When a person taking disulfiram consumes alcohol, acetaldehyde accumulates to levels 5-10 times higher than normal.
This accumulation triggers the severe and unpleasant disulfiram-ethanol reaction, which deters further alcohol use.

Why Other Options Were Wrong

Option A: Acetate is the final, less toxic product of acetaldehyde metabolism. An enzyme that breaks down acetate is not the target of disulfiram.
Option B: NADPH dehydrogenase is part of the electron transport chain and is involved in cellular energy production, which is a different metabolic pathway.
Option D: Glucose 6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway. Its deficiency leads to hemolytic anemia and is unrelated to alcohol metabolism.

Related Visual

Clinical Relevance

Nursing practice connection: This is primarily an exam-oriented knowledge point with limited direct bedside application, so retain Pharmacology: Mechanism of action of disulfiram as background academic context rather than a clinical decision trigger.
Disulfiram is used as a deterrent for chronic alcohol dependence. The fear of the severe reaction is a powerful tool to help maintain abstinence.
Nursing care requires extensive patient education to avoid all forms of alcohol, including hidden sources like mouthwash, cough syrups, aftershaves, and certain food preparations (e.g., sauces, vinegars, desserts).
The effects of disulfiram can last for up to two weeks after the last dose, so patients must be warned to continue avoiding alcohol for this period.

How to Approach the Question

This is a factual recall question about a specific drug's mechanism of action.
First, identify the drug in the question: Disulfiram.
Recall its primary clinical use, which is as an aversion therapy for alcohol dependence.
Access your knowledge of the alcohol metabolism pathway: Ethanol is converted to toxic acetaldehyde, which is then converted to harmless acetate.
Deduce that to create an 'aversion' reaction, the drug must cause a buildup of the toxic intermediate (acetaldehyde).
Therefore, the drug must block the enzyme that breaks down acetaldehyde.

Concept Tested & Keywords

Concept Tested: Pharmacology: Mechanism of action of disulfiram
Stem keywords: Disulfiram, inhibits, enzyme
Lead-in keywords: which of the following
Negative lead-in flag: false

Question ID

QJHf0mwxHraYEYXDBDZbKE

Reference Book

E6 Robert Boland, Marcia L. Verduin - Kaplan and Sadock's Comprehensive Text of Psychiatry-Wolters Kluwer Health (2024) (pp 1-16525 of 16525) p. 10936-10938

E6 Kaplan Sadock's Synopsis of Psychiatry-2022 (pp 1-3768 of 3768) pp. 2183-2185, 2185-2187

Practise the full DSSSB 12 August 2024

Attempt every question from this paper in a timed mock, then review the full solution for each one.

Attempt this paper Attempt in the NPrep app