Understanding the ACE Inhibitor Side Effect: What is bradykinin cough?

Affecting up to 35% of patients taking Angiotensin-Converting Enzyme (ACE) inhibitors, a persistent dry cough is a widely recognized side effect. Understanding what is bradykinin cough is key to managing this common pharmacological issue.

Quick Summary

A bradykinin cough is a dry, persistent cough caused by the accumulation of bradykinin, a common side effect of ACE inhibitor medications. Management involves switching to an alternative medication like an ARB.

Key Points

• Primary Cause: Bradykinin cough is a side effect of ACE inhibitors caused by bradykinin accumulation.

• Mechanism: ACE inhibitors prevent bradykinin breakdown, sensitizing airway nerves and triggering cough.

• Prevalence: The incidence ranges from 5% to 35% among patients taking ACE inhibitors.

• Definitive Treatment: Discontinuing the ACE inhibitor is the only effective treatment.

• Primary Alternative: ARBs are the main alternative as they do not affect bradykinin and have a lower cough incidence.

• Resolution Time: Cough typically resolves within 1 to 4 weeks after stopping the ACE inhibitor, possibly up to 3 months.

• Risk Factors: Risk factors include being female and older age.

The Link Between Blood Pressure Medication and a Persistent Cough

Angiotensin-converting enzyme (ACE) inhibitors are medications commonly used for high blood pressure and heart failure. A significant side effect associated with them is a persistent, dry cough. This cough, often called a bradykinin cough, affects 5% to 35% of patients. It can start hours or months after beginning treatment and is described as a tickle in the throat, sometimes severe enough to impact sleep and quality of life.

Pathophysiology: How Do ACE Inhibitors Cause a Cough?

The primary cause of ACE inhibitor-induced cough is the peptide bradykinin. The ACE enzyme converts angiotensin I to angiotensin II and also breaks down bradykinin. ACE inhibitors block this enzyme, reducing angiotensin II and preventing bradykinin breakdown. The buildup of bradykinin in the respiratory tract is the leading theory for the cough.

Increased bradykinin is thought to cause cough by:

• Sensitizing nerves: It sensitizes airway sensory nerves, particularly C-fibers, making airways hypersensitive to stimuli.
• Stimulating receptors: Bradykinin activates B2 receptors on C-fibers, starting the cough reflex.
• Producing inflammatory mediators: Bradykinin can also stimulate the release of other mediators like prostaglandins, which may further increase cough sensitivity.

Not all patients develop this cough. Research into this variation suggests factors like genetic differences in bradykinin receptor genes and individual cough reflex sensitivity may play a role.

Identifying and Managing a Bradykinin Cough

Characteristics and Diagnosis

A bradykinin cough is typically dry, persistent, and non-productive. It often worsens at night.

Diagnosis is clinical; a chronic cough starting after beginning an ACE inhibitor is considered likely caused by the medication. The cough usually stops within 1 to 4 weeks after discontinuing the drug, though it can take up to 3 months.

Treatment and Alternatives

The only effective treatment is stopping the ACE inhibitor. Standard cough medicines are usually ineffective. For ongoing treatment, ARBs are the most recommended alternative.

Comparison: ACE Inhibitors vs. Angiotensin II Receptor Blockers (ARBs)

Feature	Angiotensin-Converting Enzyme (ACE) Inhibitors	Angiotensin II Receptor Blockers (ARBs)
Mechanism	Block the ACE enzyme, preventing angiotensin II formation and bradykinin breakdown.	Directly block angiotensin II receptors, leaving bradykinin unaffected.
Effect on Bradykinin	Increase bradykinin levels.	Do not increase bradykinin levels.
Cough Incidence	Significantly higher (5-35%).	Much lower, comparable to placebo.
Angioedema Risk	Higher risk.	Lower risk.

ARBs provide similar benefits to ACE inhibitors but without increasing bradykinin, making them a good option for those with cough.

Conclusion

A bradykinin cough is a known side effect of ACE inhibitors caused by bradykinin buildup in the airways. This dry, persistent cough can be bothersome but is not harmful and can be managed. The main solution is stopping the ACE inhibitor and switching to an ARB, which offers similar benefits without causing the cough. Discuss this with a healthcare provider for diagnosis and treatment adjustments.

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For further reading, an authoritative review can be found in the National Center for Biotechnology Information (NCBI) database. {Link: NCBI https://pmc.ncbi.nlm.nih.gov/articles/PMC7670268/}

Frequently Asked Questions

How long does it take for a bradykinin cough to go away after stopping an ACE inhibitor?

The cough typically resolves within 1 to 4 weeks after discontinuing the ACE inhibitor. However, in a subgroup of patients, the cough may persist for up to 3 months.

Is a bradykinin cough dangerous?

No, the cough itself is not considered harmful, but it can be very persistent and negatively affect a person's quality of life by interfering with sleep and daily activities.

Can I get a bradykinin cough from any blood pressure medication?

No, the bradykinin cough is a specific side effect of the ACE inhibitor class of medications. Other classes, like Angiotensin II Receptor Blockers (ARBs), have a much lower risk of causing cough.

Are there any treatments for the cough besides stopping the medication?

The only uniformly effective treatment is to stop taking the ACE inhibitor. While some small studies have investigated agents like cromolyn or certain NSAIDs, switching to an alternative medication like an ARB is the standard and most effective management strategy.

Why don't ARBs cause a cough like ACE inhibitors do?

ARBs work by blocking the receptors for angiotensin II, rather than inhibiting the ACE enzyme. This means they do not interfere with the breakdown of bradykinin, so bradykinin does not accumulate in the airways to trigger a cough.

Can I develop a bradykinin cough after taking an ACE inhibitor for years?

Yes. The onset of an ACE inhibitor-induced cough can range from within hours of the first dose to weeks or even months after starting therapy.

Are some people more likely to get a bradykinin cough?

Yes, studies have identified several risk factors. The cough is more common in women, older individuals, and some research suggests a higher prevalence in certain racial backgrounds and those with specific genetic polymorphisms related to bradykinin receptors.