THERAPEUTIC ACTIONS ã…¡ 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.
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.
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
INTERACTIONS
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 these drugs 1 hour before or 2 hours after meals; do not take with food (captopril).
- Do not stop taking the medication without consulting your pharmacist or physician.
- Be careful with any conditions that may lead to a drop in blood pressure (such as diarrhea, sweating, vomiting, dehydration); if light-headedness or dizziness occurs, consult your health care provider.
- Avoid over-the-counter drugs, especially cough, cold, allergy medications. If you need one of these, consult your health care provider.
- You may experience these side effects: GI upset, loss of appetite, change in taste perception (limited effects; if they persist or become a problem, consult your health care provider); mouth sores (frequent mouth care may help); rash; fast heart rate; dizziness, light-headedness (passes after a few days of therapy; if it occurs, change position slowly and limit activities requiring alertness and precision); cough.
- Report mouth sores; sore throat, fever, chills; swelling of the hands, feet; irregular heartbeat, chest pains; swelling of the face, eyes, lips, tongue; difficulty breathing.
MEDICATIONS
| Table (1). Comparison of Angiotensin-Converting Enzyme Inhibitors | |||
|---|---|---|---|
| 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. | |||
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