Angiotensin II Receptor Blockers (ARBs) are a common class of medication prescribed to manage high blood pressure and other cardiovascular conditions. While an older, related group of blood pressure drugs is frequently associated with an irritating, persistent dry cough, ARBs are known for rarely causing this side effect. This difference in side effect profile is a primary reason why ARBs are often used as an alternative treatment for patients who cannot tolerate the persistent cough caused by other medications. Understanding the distinct ways these drug classes work on the body’s systems explains why the ARB-related cough is so unusual.
Understanding the Common Medication Cough
The persistent dry cough associated with certain blood pressure medications is a well-documented side effect of Angiotensin-Converting Enzyme (ACE) Inhibitors. ACE Inhibitors work by blocking the action of the Angiotensin-Converting Enzyme, which transforms Angiotensin I into the potent blood vessel constrictor, Angiotensin II. By interfering with this enzyme, the medication reduces Angiotensin II, leading to blood vessel relaxation and reduced blood pressure.
The enzyme is also responsible for breaking down bradykinin, a naturally occurring inflammatory substance. When an ACE Inhibitor blocks the enzyme, this leads to an accumulation of bradykinin in the airways and lungs, which triggers the cough. Bradykinin sensitizes sensory nerves, increasing cough reflex sensitivity.
This cough typically presents as a non-productive, dry, and persistent hack that can develop anywhere from a few days to several months after starting the medication. This side effect is common, affecting an estimated 5% to 35% of patients taking ACE inhibitors.
The Unique Action of ARBs
Angiotensin II Receptor Blockers (ARBs) target the same system as ACE Inhibitors but intervene at a different point in the biological pathway. ARBs work “downstream” by selectively blocking the Angiotensin II Type 1 (AT1) receptor, and they do not interact with the Angiotensin-Converting Enzyme itself.
Angiotensin II must bind to the AT1 receptor to exert its effects, such as constricting blood vessels. By blocking the receptor, the ARB prevents Angiotensin II from connecting and initiating the chain of events that leads to elevated blood pressure. This mechanism achieves the goal of lowering blood pressure without affecting the production of the hormone.
Why ARBs Rarely Trigger a Cough
ARBs rarely trigger a persistent dry cough because they do not inhibit the Angiotensin-Converting Enzyme. Since the enzyme remains fully active in the body, it is still able to metabolize and clear bradykinin from the airways.
Because bradykinin is broken down efficiently and does not accumulate, the main biological trigger for the drug-induced cough is avoided. The incidence of cough with ARBs is similar to that of a placebo, meaning the drug itself is unlikely to be the cause. The risk of developing a cough while taking an ARB is estimated to be below 2%, which is significantly lower than the rate seen with ACE inhibitors.
Identifying the Rare ARB-Related Cough
A cough may still occur in rare instances while taking an ARB, but it is often due to a cause unrelated to the medication, such as an infection, allergies, asthma, or gastroesophageal reflux disease (GERD). The mechanism for the occasional ARB-related cough is not fully understood, but it is theorized to involve secondary effects on other inflammatory pathways or individual patient hypersensitivity.
If a persistent cough develops, the patient must consult their healthcare provider to determine the cause. The provider will need to differentiate the cough from other common etiologies (differential diagnosis). Stopping the ARB temporarily may be necessary to confirm if the drug is truly the source of the irritation.