Why ACE inhibitors cause a dry cough, and how it links to angioedema

One enzyme, two jobs: angiotensin and bradykinin

ACE inhibitors such as lisinopril lower blood pressure by stopping angiotensin I from being converted into angiotensin II, a powerful vasoconstrictor that also stimulates aldosterone release. Less angiotensin II means relaxed vessels and less sodium and water retention. That is the intended effect in hypertension, heart failure and kidney protection.

The same enzyme is identical to kininase II, which degrades bradykinin, a peptide that dilates vessels and makes them leaky. Blocking ACE therefore raises bradykinin levels as well. Some of this extra bradykinin may add to the blood pressure benefit, but it is also presumed to be the cause of the two adverse effects that matter most for nursing: dry cough and angioedema.

How bradykinin build-up turns into a cough

Bradykinin and related inflammatory mediators are thought to sensitise cough receptors in the airway, producing a tickly, persistent, nonproductive cough. It is not caused by infection or fluid in the lungs, so the client typically has no fever, no sputum and clear breath sounds. The cough is common, and reported rates vary between populations.

Because the cough is a drug effect, it usually resolves after the ACE inhibitor is stopped, although this can take some time. Cough suppressants do little because they do not remove the cause. For the nurse, a new dry cough after starting an ACE inhibitor is something to document and report, not a reason for the client to stop the medicine independently.

The angioedema link and why it is the bigger danger

Excess bradykinin also increases vascular permeability, letting fluid leak into deep tissue. This produces angioedema: swelling of the face, lips, tongue, glottis or larynx, and occasionally the intestine, causing abdominal pain. It can occur at any point during treatment, not only in the first weeks, and has been reported more often in Black clients.

Airway swelling is an emergency. Stop the drug, call for help, assess airway and breathing continuously and prepare emergency treatment and airway equipment under local protocol. Because it is bradykinin driven rather than histamine driven, it may respond less predictably to standard allergy treatment. A client who has had ACE inhibitor angioedema should not be restarted on any ACE inhibitor.

Why an ARB is often the substitute

Angiotensin II receptor blockers, such as losartan, block angiotensin II at its receptor instead of blocking the enzyme. They provide similar blood pressure and kidney benefits but do not interfere with bradykinin breakdown, so they are not associated with the characteristic cough. That is why the prescriber commonly switches a client with an intolerable cough to an ARB.

Some cautions carry over. ACE inhibitors and ARBs both raise potassium, especially in kidney disease or with potassium-sparing drugs, and both are contraindicated in pregnancy because of fetal harm. The two classes are not normally combined. After angioedema, the decision about any ARB rests with the prescriber, so the nurse reports the history clearly rather than assuming a switch is safe.

Apply the mechanism to a hypothetical question

A hypothetical client started on lisinopril six weeks ago reports a dry tickly cough that keeps them awake. Lungs are clear, temperature is normal and there is no swelling. Options are to give a cough suppressant and continue, tell the client to stop the drug today, collect a sputum culture, or document and report the cough so the prescriber can consider an ARB. Reporting is best.

The cough fits bradykinin accumulation, so suppressants and sputum tests miss the cause. Stopping a blood pressure drug without a plan risks uncontrolled hypertension. Change the scenario to include tongue swelling and a hoarse voice, and the priority shifts to airway protection and emergency escalation, because that suggests bradykinin-mediated angioedema rather than a nuisance side effect.

Sources and further reading

DailyMed: Lisinopril and hydrochlorothiazide tablets prescribing information. ACE identical to kininase, bradykinin as presumed cause of nonproductive cough, resolution after stopping, angioedema of head, neck and intestine, airway management, hyperkalaemia and fetal toxicity.

MSD Manual Professional: Medications for hypertension. ACE inhibitors inhibit bradykinin breakdown, cough rates vary by population, angioedema risk, ARBs as an alternative for cough, potassium and pregnancy cautions.

MedlinePlus: Lisinopril. Cough as a side effect, urgent reporting of facial or throat swelling and breathing difficulty, and pregnancy warning.