Why do ace inhibitors cause cough
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Mechanisms Behind ACE Inhibitor-Induced Cough
Introduction to ACE Inhibitor-Induced Cough
Angiotensin-converting enzyme (ACE) inhibitors are widely used for treating cardiovascular diseases, including hypertension and heart failure. However, a common adverse effect associated with these medications is a persistent, dry cough. This side effect can be bothersome enough to necessitate discontinuation of the drug in some patients .
Incidence and Onset of ACE Inhibitor-Induced Cough
The incidence of ACE inhibitor-induced cough varies widely, reported to affect between 5% and 35% of patients . The onset of the cough can range from hours after the first dose to several months into the therapy. Women appear to be more susceptible to this side effect than men, although the exact reasons for this difference are not fully understood .
Mechanisms Involved in ACE Inhibitor-Induced Cough
Role of Bradykinin and Substance P
The primary mechanism behind ACE inhibitor-induced cough is believed to involve the accumulation of bradykinin and substance P. These protussive mediators are normally degraded by ACE. When ACE is inhibited, these substances accumulate in the respiratory tract, leading to stimulation of the cough reflex . Bradykinin, in particular, may also stimulate the production of prostaglandins, which further contribute to the cough .
Inflammatory Response and Bronchial Reactivity
ACE inhibitors may also induce an inflammatory state in the airways, which can enhance bronchial reactivity and lead to cough. This inflammatory response is characterized by increased infiltration of neutrophils and eosinophils, similar to the early symptoms of asthma. Additionally, ACE inhibition has been shown to increase the cough reflex, making patients more susceptible to coughing .
Management and Treatment of ACE Inhibitor-Induced Cough
Discontinuation of ACE Inhibitors
The most effective treatment for ACE inhibitor-induced cough is the cessation of the offending agent. The cough typically resolves within 1 to 4 weeks after stopping the medication, although it can persist for up to 3 months in some cases . Switching to an angiotensin receptor blocker (ARB) is often recommended, as these medications do not cause the same accumulation of bradykinin and substance P .
Pharmacologic Interventions
While discontinuation is the primary treatment, some pharmacologic agents have been explored to attenuate the cough. However, the effectiveness of these interventions varies, and they are not universally recommended . Nonsteroidal anti-inflammatory drugs (NSAIDs) and inhaled cromoglycate have shown some promise in reducing the cough, but their use is not widespread due to limited efficacy and practicality.
Conclusion
ACE inhibitor-induced cough is a common and often troublesome side effect that can significantly impact patient compliance. The primary mechanisms involve the accumulation of bradykinin and substance P, leading to increased cough reflex and airway inflammation. Discontinuation of the ACE inhibitor remains the most effective treatment, with ARBs serving as a suitable alternative. Understanding these mechanisms can help healthcare providers better manage and mitigate this adverse effect, ensuring optimal patient outcomes.
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