Angiotensin-converting enzyme (ACE) inhibitors

This topic will discuss the pharmacological point of angiotensin converting enzyme (ACE) inhibitors.

Therapeutic actions

ACE inhibitors block ACE in the lungs from converting angiotensin 1, activated when renin is released from the kidneys, to angiotensin 2, a powerful vasoconstrictor. Blocking this conversion leads to decreased BP, decreased aldosterone secretion, a small increase in serum potassium levels, and sodium and fluid loss; increased prostaglandin synthesis also may be involved in the antihypertensive action.

NPS-adv

Clinical pharmacology

Indications

Treatment of hypertension (alone or with thiazide-type diuretics), treatment of heart failure (used with diuretics and digitalis), treatment of stable patients within 24 hr of acute MI to improve survival (lisinopril), reduction in risk of MI, stroke, and death from CV causes (ramipril), treatment of left ventricular dysfunction post-MI (captopril, trandolapril), treatment of asymptomatic left ventricular dysfunction (enalapril), treatment of diabetic nephropathy (captopril). Unlabeled uses include renovascular hypertension, nondiabetic nephropathy, migraine prophylaxis, stroke prevention, heart failure, high risk of CAD, diabetes, chronic renal disease, scleroderma renal crisis.

Agent Availability Dosages Considerations
Benazepril (Lotensin) 5, 10, 20, 40 mg HTN
Start: 10 mg daily
Target: 20 to 40 mg daily
Maximum: 80 mg daily
Captopril (Capoten) 12.5, 25, 50, 100 mg HTN Food decreases absorption, but blood levels do not correlate with blood pressure response
25 to 50 mg two or three times daily
CHF
Start: 6.25 to 25 mg three times daily
Target: 50 to 100 mg three times daily
LVD/MI
Start: 6.25 mg daily
Target: 50 mg three times daily
DN
25 mg three times daily
Maximum: 450 mg daily
Enalapril (Vasotec) 2.5, 5, 10, 20 mg HTN
Start: 5 mg daily
Range: 10 to 40 mg once daily or in two divided doses
CHF
Start: 2.5 mg daily
Target: 40 mg daily in two divided doses
ALVD
Start: 2.5 mg twice daily
Target: 20 mg daily in two divided doses
Maximum: 40 mg daily
Fosinopril (Monopril) 10, 20, 40 mg HTN May cause false low serum digoxin levels

Patients with impaired liver function may have elevated plasma levels
Start: 10 mg daily
Target: 40 mg daily
CHF
Start: 10 mg daily
Target: 20 to 40 mg daily
Maximum: 80 mg daily
Lisinopril (Zestril) 2.5, 5, 10, 20, 30, 40 mg HTN
Start: 10 mg daily
Target: 20 to 40 mg daily
CHF
Start: 5 mg daily
Target: 20 mg daily
AMI
Start: 5 mg daily for two days, then 10 mg daily for six weeks, then re-evaluate
Maximum: 40 mg daily
Moexipril 7.5, 15 mg HTN
Start: 7.5 mg daily one hour before meals
Target: 7.5 to 30 mg in one dose or two divided doses one hour before meals
Maximum: 30 mg daily
Perindopril 2, 4, 8 mg HTN Cautious administration with gentamicin
Start: 4 mg daily
Target: 4 to 8 mg daily
Maximum: 16 mg daily
Quinapril 5, 10, 20, 40 mg HTN Food decreases absorption
Start: 10 mg daily
Target: 80 mg daily
CHF
Start: 5 mg twice daily, titrate weekly to 20 to 40 mg in divided doses
Maximum: 80 mg daily
Ramipril 1.25, 2.5, 5, 10 mg HTN Patients with impaired liver function may have elevated plasma levels
Start: 2.5 mg daily
Target: 2.5 to 20 mg daily in one dose or two divided dose
CHF/MI
Start: 2.5 mg twice daily
Target: 5 mg twice daily
RR: 10 mg daily
Maximum: 20 mg daily
Trandolapril 1, 2, 4 mg HTN Food decreases absorption
Start: 1 mg daily (2 mg daily in black patients)
Target: 2 to 4 mg per day
CHF/MI
Start: 1 mg daily
Target: 4 mg daily
LVD/MI
Start: 1 mg daily
Target: 4 mg daily
Maximum: 8 mg daily
ALVD = asymptomatic left ventricular dysfunction; AMI = acute myocardial infarction; CHF = congestive heart failure; CHF/MI = heart failure after myocardial infarction; DN = diabetic nephropathy; HTN = hypertension; LVD/MI = left ventricular dysfunction after myocardial infarction; RR = risk reduction of cardiovascular events in at-risk patients.

Contraindications

Contraindicated with allergy to the drug, impaired renal function, heart failure, salt or volume depletion, lactation, pregnancy, history of angioedema, bilateral renal artery stenosis. Pregnancy category C (first trimester) and pregnancy category D (second and third trimesters).

Adverse effects

Increased risk of hypersensitivity reactions with allopurinol. Decreased antihypertensive effects with indomethacin. Increased risk of hyperkalemia if combined with aldosterone blockers, potassium-sparing diuretics, aliskiren, cyclosporine, potassium supplements.

NPS-adv

Teaching points

Take captopril one hour before or two hours after meals, as it should not be taken with food. Do not discontinue the medication without consulting your pharmacist or physician. Be cautious of conditions that may lead to a drop in blood pressure, such as diarrhea, sweating, vomiting, or dehydration; if you experience light-headedness or dizziness, seek advice from your health care provider. Avoid over-the-counter medications, particularly those for cough, cold, or allergies, unless you have consulted your health care provider. Possible side effects include gastrointestinal upset, loss of appetite, and changes in taste perception—though these effects are typically limited. If side effects persist or become troublesome, consult your health care provider. Other side effects may include mouth sores (which frequent oral care might alleviate), rash, a rapid heartbeat, and dizziness or light-headedness, which usually resolve after a few days of treatment. If dizziness occurs, change positions slowly and limit activities that require alertness. Persistent side effects such as mouth sores, sore throat, fever, chills, swelling in the hands or feet, irregular heartbeat, chest pains, facial swelling, or difficulty breathing should be reported to your health care provider immediately.


References

  1. Mauer M, et al. Renal and retinal effects of enalapril and losartan in type 1 diabetes. N Engl J Med. 2009;361(1):40-51.
  2. Herman, L.L. and Bashir, K. (2019). Angiotensin Converting Enzyme Inhibitors (ACEI). [online] Nih.gov. Available at: https://www.ncbi.nlm.nih.gov/books/NBK431051.
  3. Arauz-Pacheco C, Parrott MA, Raskin P, et al. Hypertension management in adults with diabetes. Diabetes Care. 2004;27 Suppl 1:S65-7.