Therapeutic actions ㅡ 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.
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
- CNS: Dizziness, headache, fatigue
- CV: Tachycardia, angina pectoris, MI, Raynaud's syndrome, heart failure, hypotension in salt- or volume-depleted patients
- Dermatologic: Rash, pruritus, alopecia, pemphigoid-like reaction, scalded mouth sensation, exfoliative dermatitis, photosensitivity
- GI: Gastric irritation, aphthous ulcers, peptic ulcers, dysgeusia, cholestatic jaundice, hepatocellular injury, anorexia, constipation
- Renal: Proteinuria, renal insufficiency, renal failure, polyuria, oliguria, urinary frequency
- Hematologic: Neutropenia, agranulocytosis, thrombocytopenia, hemolytic anemia, pancytopenia, hyperkalemia
- Other: Cough, malaise, dry mouth, lymphadenopathy, angioedema
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.
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
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Mauer M, Zinman B, Gardiner R, et al. Renal and retinal effects of enalapril and losartan in type 1 diabetes. N Engl J Med. 2009;361(1):40-51. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa0808400
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
Arauz-Pacheco C, Parrott MA, Raskin P, et al. Hypertension management in adults with diabetes. Diabetes Care. 2004;27 Suppl 1:S65-7. Available at: https://diabetesjournals.org/care/article/27/suppl_1/s65/24606/Hypertension-Management-in-Adults-With-Diabetes
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