A 62-year-old man with hypertension is started on enalapril. After 3 weeks, he develops a persistent dry cough. The cough resolves completely after switching to losartan. Which of the following statements about this adverse drug reaction is NOT true?
A. It occurs due to accumulation of bradykinin in the lungs
B. It is a Type B (bizarre) adverse drug reaction independent of dose
C. It is a Type A (augmented) adverse drug reaction
D. It is dose-dependent and predictable from the drug's pharmacology
Explanation
Classification of ACE Inhibitor-Induced Cough
Type A vs Type B Adverse Reactions
Key Point
ACE inhibitor-induced cough is a Type B (bizarre/idiosyncratic) reaction, not Type A. This is a high-yield distinction in ADR classification.
Table
Feature
Type A (Augmented)
Type B (Bizarre)
Mechanism
Exaggeration of known pharmacological action
Unpredictable, unrelated to primary intended action
Dose-dependent
Yes, increases with dose
No, independent of dose
Predictability
Predictable from pharmacology
Idiosyncratic, occurs in susceptible individuals
Incidence
Common
Relatively uncommon (5–20% of ACE inhibitor users)
Example
Beta-blocker bradycardia, hypoglycaemia with insulin
ACE inhibitor cough, penicillin anaphylaxis
Why ACE Inhibitor Cough is Type B
1.
Mechanism: ACE inhibitors block the breakdown of bradykinin, leading to its accumulation in the lungs. Bradykinin stimulates cough receptors → dry, persistent cough.
2.
Not dose-dependent: The cough does not reliably increase with higher doses and does not resolve simply by reducing the dose — it requires discontinuation of the drug.
3.
Idiosyncratic/unpredictable: Only a subset of patients (5–20%) develop cough despite all patients experiencing ACE inhibition. It is not a direct extension of the primary therapeutic action (lowering blood pressure), making it Type B.
4.
Confirmed by switching: Resolution on switching to losartan (ARB) confirms the bradykinin-mediated mechanism, but the unpredictable occurrence in a subset of patients is the hallmark of Type B.
High-Yield (KD Tripathi / Rang & Dale): ACE inhibitor cough is classified as Type B because it is an idiosyncratic reaction occurring in susceptible individuals, is not dose-dependent, and is unrelated to the primary pharmacological action (antihypertensive effect). Type A reactions are direct, dose-dependent extensions of the drug's main pharmacological effect (e.g., excessive hypotension with antihypertensives).
What is NOT True
Option A ("It is a Type A reaction") — This is NOT true. ACE inhibitor cough is Type B, not Type A.
Option B ("It is dose-dependent and predictable") — This is also NOT true of ACE inhibitor cough; however, Option A is the more direct false statement about classification.
Option C ("Bradykinin accumulation") — This IS true; bradykinin accumulation is the established mechanism.
Option D ("It is a Type B reaction independent of dose") — This IS true.
Clinical Pearl
The question asks which statement is NOT true. Option A (calling it Type A) is the false statement. Option D correctly identifies it as Type B.
Mnemonic
Type A = Augmented (exaggerated normal effect, dose-dependent); Type B = Bizarre (idiosyncratic, dose-independent, occurs in susceptible individuals).
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