Angiotensin-converting enzyme (ACE) inhibitors

Angiotensin-converting enzyme (ACE) inhibitors

Angiotensin II (ATII) is a highly potent endogenous vasoconstrictor. It is formed from angiotensin I in the blood by the angiotensin converting enzyme (ACE). The renin–angiotensin-aldosterone system (RAAS) modulating actions of ATII are mediated by the angiotensin receptors AT1 and AT2

ACE inhibitors partially prevent the conversion of ATI to ATII. As a result, blood vessels dilate, and blood pressure is reduced. Reducing blood pressure makes it easier for the heart to pump blood and can improve the function of a failing heart. An additional clinical intervention delivered by ACE inhibitors is slowing progression of kidney disease due to high blood pressure or diabetes.

ACE inhibitors are the first-line choice in hypertension treatment, especially in those under 55 years old. Using ACE inhibitors to treat heart failure is not so age dependent, and the level of benefit achieved seems to increase with age. Angiotensin receptor antagonist type drugs are often used in patients intolerant to ACE inhibitors, and prove useful as they inhibit the activity of residual ATII present in the blood due to incomplete ACE inhibition. The combination therapy of angiotensin receptor antagonists with ACE inhibitors may be superior to either agent alone.

ACE inhibitors are administered as prodrugs or prodrug conjugates, which are metabolised in the liver to the active compound. ACE inhibitor prodrugs have the generic name stem suffix '-pril', and the active compound has the stem '-prilat'.

Captopril was the first ACE inhibitor to be approved, but has since been superseded by alternatives with improved duration of action and fewer adverse effects. There is a wide choice of ACE inhibitors available to the prescriber, but all have similar antihypertensive activity at equivalent doses. The main difference between the different drugs is their duration of action. Some of those available are listed below, along with equivalent dose information.

ACE inhibitors dosages for hypertension

Name Eq. daily dose Start dose Usual dose Max. dose
benazepril 10mg 10mg 20-40mg 80mg
captopril 50mg (25mg bid) 12.5-25mg bid-tid 25–50mg bid-tid 450mg/day
enalapril 5mg 5mg 10-40mg 40mg
fosinopril 10mg 10mg 20-40mg 80mg
lisinopril 10mg 10mg 10-40mg 80mg
moexipril 7.5mg 7.5mg 7.5-30mg 30mg
perindopril 4mg 4mg 4-8mg 16mg
ramipril 2.5mg 2.5mg 2.5-20mg 20mg
trandolapril 2mg 1mg 2-4mg 8mg
quinapril 10mg 10mg 20-80mg 80mg
tid = three times a day bid = two times a day

All ACE inhibitors are contra-indicated in patients with previous ACE inhibitor-induced angiodema, or hypersensitivity to the drug. Prescribers should be cautious of prescribing ACE inhibitors to patients with renal impairment, aortic valve stenosis or cardiac outflow obstruction, hypovolemia, dehydration or those on hemodialysis (using high-flux polyacrylonitrile membranes). Administration of ACE inhibitors to women who are likely to become pregnant should be avoided, as should use during pregnancy due to risk of drug-induced birth defects. A mnemonic to aid recollection of ACE inhibitor contra-indications is PARK: Pregnancy, Allergy/Angiodema, Renal failure, K- hyperkalemia (potassium >5.5).

Side effects include a dry, irritating cough and more rarely renal stenosis or allergic reaction.

Renin Angiotensin Aldosterone System (RAAS) - Short and sweet!

This 7 minute animation reviews the important organs, hormones, enzymes and mechanisms by which the RAAS system controls blood pressure.

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