Lisinopril causes cough
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Lisinopril and Its Association with Cough: A Comprehensive Review
Introduction to Lisinopril-Induced Cough
Lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, is widely used for treating hypertension and heart failure. However, a notable side effect associated with its use is the development of a persistent dry cough. This article synthesizes findings from multiple studies to provide a clear understanding of the incidence, severity, and mechanisms behind lisinopril-induced cough.
Incidence of Cough with Lisinopril
Comparative Studies on Cough Incidence
Several studies have consistently shown that the incidence of cough is significantly higher in patients treated with lisinopril compared to other antihypertensive agents. For instance, a study comparing lisinopril, losartan (an angiotensin II receptor antagonist), and hydrochlorothiazide (a diuretic) found that 72% of patients on lisinopril reported cough, compared to 29% on losartan and 34% on hydrochlorothiazide . Another study reported a 60% incidence of cough with lisinopril, significantly higher than the 15.6% with telmisartan and 9.7% with placebo.
Gender and Smoking Status Influence
The incidence of cough appears to be influenced by gender and smoking status. Women treated with lisinopril reported cough three times more often than men (12.6% vs. 4.4%). Additionally, nonsmokers reported an increase in cough more frequently than smokers.
Severity and Frequency of Cough
Visual Analogue Scale Assessments
The severity and frequency of cough in patients on lisinopril have been assessed using visual analogue scales. Studies have shown that patients on lisinopril rated their cough frequency significantly higher than those on losartan or placebo . For example, one study found that the mean visual analogue scale scores for cough frequency were significantly higher in the lisinopril group compared to the losartan and placebo groups.
Mechanisms Behind Lisinopril-Induced Cough
Role of Bradykinin and Substance P
The mechanism behind lisinopril-induced cough is believed to be related to the accumulation of bradykinin and substance P, which are not adequately broken down due to ACE inhibition. This accumulation can lead to increased sensitivity of the cough reflex. Studies involving animal models have shown that lisinopril, but not losartan, increases the cough response induced by both mechanical and chemical stimulation .
Central Nervous System Involvement
Research suggests that lisinopril may also have a central protussive action. Microinjections of lisinopril into the caudal nucleus tractus solitarii of rabbits increased the cough number, an effect that was reversed by bradykinin and substance P antagonists. This indicates a central mechanism in addition to the peripheral effects.
Conclusion
Lisinopril is associated with a significantly higher incidence, severity, and frequency of cough compared to other antihypertensive agents such as losartan and hydrochlorothiazide. The underlying mechanisms involve the accumulation of bradykinin and substance P, which enhance the cough reflex. Understanding these factors is crucial for clinicians in managing patients who develop this troublesome side effect, potentially opting for alternative treatments like angiotensin II receptor antagonists.
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