- Clinical science
Renin-angiotensin-aldosterone system (RAAS) inhibitors are a group of drugs that act by inhibiting the renin-angiotensin-aldosterone system (RAAS) and include angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), and direct renin inhibitors. ACE inhibitors and ARBs are commonly used in the treatment of patients with hypertension, heart failure with reduced ejection fraction, certain types of chronic kidney disease, and patients who have suffered a myocardial infarction. They are particularly important in the treatment of hypertensive diabetic patients, as they prevent the development of diabetic nephropathy. A common side effect of ACE inhibitors is a bradykinin-induced cough, which may necessitate switching to an alternative therapy (e.g. ARBs), while angioedema and hyperkalemia may occur in both ARBs and ACE inhibitor use. Direct renin inhibitors may be considered in hypertensive patients if ACE inhibitors or ARBs are not well tolerated; however, they should never be used in combination with other RAAS inhibitors.
- Drops in blood pressure reduce renal perfusion.
- If the pressure in the renal artery falls by more than 10–15 mm Hg → proteolytic renin is released from the juxtaglomerular apparatus → renin converts angiotensinogen to angiotensin I → ACE cleaves C-terminal peptides on angiotensin I, converting it to angiotensin II → increases the blood pressure in two ways: (1) vasoconstriction and (2) stimulation of the release of aldosterone, which increases the retention of water and sodium
Types of RAAS inhibitors
|ACE inhibitors||Enalapril, lisinopril, ramipril, captopril, benazepril|| |
|Direct renin inhibitors||Aliskiren|
|Mechanism of action and effect|
|ACE inhibitors|| |
|ARBs (sartans)|| |
|Direct renin inhibitors|
Dry cough due to increase in bradykinin concentration →
- Treat by discontinuing ACE inhibitor; consider switching to
- Pemphigus vulgaris (unknown mechanism)
We list the most important adverse effects. The selection is not exhaustive.
Contraindications for ACE inhibitors and ARBs
- Absolute contraindications
- Relative contraindications
Contraindications for direct renin inhibitors
- Drug interactions (see “Interactions” below)
Normally, angiotensin II constricts efferent vessels and thereby increases the GFR. ACE inhibitors antagonize the conversion of angiotensin I to angiotensin II, thereby reducing the GFR!
We list the most important contraindications. The selection is not exhaustive.
- ACE inhibitors and ARBs
- Direct renin inhibitors
- Starting with low doses (preferably in controlled setting) is recommended to avoid severe hypotension!
- Combine ACE inhibitors or ARBs with thiazide diuretics to offset the risks of hyperkalemia and hypokalemia.
- When starting an ACE inhibitor or an ARB, monitor blood pressure, potassium, and creatinine.