What are the Side Effects of ACE Inhibitors and ARBs?
When studying these drugs, it’s helpful to be familiar with the renin-angiotensin-aldosterone system, which plays an important role in regulating blood pressure and fluid balance. Renin, which is released by the kidneys, stimulates the formation of angiotensin in blood and tissues, which in turn stimulates the release of aldosterone from the adrenal cortex. If the RAA system is abnormally active, blood pressure will be too high.There are many drugs that interrupt different steps in this system to lower blood pressure.
ACE inhibitors are considered ‘first-line therapy’ in the treatment of stage 1 hypertension. The angiotensin-converting enzyme (ACE) is mainly located in the endothelial lining of blood vessels, which is where most angiotensin II is produced. ACE inhibitors block this enzyme that normally converts angiotensin I to angiotensin II, a powerful vasoconstrictor. By blocking the production of angiotensin II, ACE inhibitors decrease vasoconstriction (causing vasodilation), and decrease aldosterone production (which reduces the retention of sodium and water).
Because these drugs are effective in treating hypertension, they also have beneficial effects on the heart, blood vessels, and kidneys. Therefore, they are also used to treat heart failure because they decrease peripheral vascular resistance, cardiac workload, and ventricular remodeling (changes to the heart resulting from injury to the heart muscle). ACE inhibitors are often used in conjunction with a diuretic in treating hypertension and heart failure. They are also given to improve post-MI survival, when added to the standard therapy of aspirin, a beta blocker, and a thrombolytic. Specific drugs include captopril (the first ACE inhibitor marketed), benazepril, enalapril (Vasotec), fosinopril, lisinopril, moexipril, quinapril, and ramipril. Note that each ACE inhibitor ends with ‘pril.’ Ace inhibitors are well absorbed orally, producing effects within 1 hour that last approximately 24 hours.
Overall, they are well-tolerated and have a low incidence of side effects. There is however, a common annoying side effect of persistent coughing that affects 10-20% of patients. Hypotension can also be a problem when an ACE inhibitor is started, especially in patients with fluid volume deficit. Hyperkalemia may also develop in patients with diabetes or renal impairment, those taking NSAIDs, potassium supplements, or potassium-sparing diuretics. ACE inhibitors are contraindicated during pregnancy and have a black box warning, as their use can cause injury and even death to a developing fetus.
Angiotensin II Receptor Blockers (ARBs) have very similar effects to ACE inhibitors and are also used for hypertension, heart failure, and post-MI. However, their mechanism of action is very different. Instead of inhibiting the formation of angiotensin II, as ACE inhibitors do, ARBs compete with angiotensin II for tissue binding sites and block the angiotensin II receptors on blood vessels and the heart, causing a decrease in arterial blood pressure by decreasing systemic vascular resistance. ARBs are similar to ACE inhibitors in their effects on blood pressure and are as effective as ACE inhibitors in the management of hypertension and heart failure. They have a low incidence of side effects and do not cause a persistent cough or hyperkalemia. Patients with bilateral renal artery stenosis should not be given ARBs or ACE inhibitors, because they both can lead to renal failure in that particular patient.
Overall, the drugs are well tolerated, but there is a black box warning during pregnancy. Specific drugs include candesartan, eprosartan, irbesartan, losartan (the first ARB), olmesartan, telmisartan, azilsartan, and valsartan. Valsartan is the only ARB approved for post-MI. Note that each ARB ends with ‘sartan.’ Some ARBs are combined with hydrochlorothiazide (HCTZ), if they are not effectively controlling blood pressure when given alone.
Let’s look at a couple of questions to review…
When giving discharge instructions to a patient that has just started taking an ACE inhibitor, the nurse should let the patient know that which of the following is a common adverse reaction to therapy with an ACE inhibitor?
- Muscle weakness
- Dry, non productive, persistent cough
Number 3 is right! A persistent cough is a common side effect of an ACE inhibitor due to the increase in bradykinin levels.
A patient tells the nurse that he has not been able to tolerate lisinopril and wants to be sure he will be given a different blood pressure medication when he goes home from the hospital. The nurse should check that his medication is replaced with which type of equally effective antihypertensive?
- Angiotensin receptor blocker
- Beta blocker
- Calcium channel blocker
If you chose #2, angiotensin receptor blocker, you’re right! ARBs have very similar effects to ACE inhibitors, without the side effects.
Great job! Thank you for watching this video on the antihypertensives – ACE inhibitors and ARBs. Be sure to check out our other videos!