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Lipika Samal M.D. and Paul A. Pham, Pharm.D.
04-14-2010
- ACE inhibitors: high affinity for angiotensin converting enzyme competing with angiotensin I, the natural substrate, to block its conversion to angiotensin II. Angiotensin II is a potent vasoconstrictor and a negative feedback mediator for renin activity. Thus, as a result of lower angiotensin II plasma levels, blood pressure decreases and plasma renin activity increases.
- Benazepril: 10 mg once daily in patients initial dose (not on a diuretic). Usual dose: 20-40 mg in a single or 2 divided doses.
- Captopril: CHF/ HTN: 6.25-12.5 mg three times a day (with diuretic) with goal of 50 mg three times a day. Diabetic nephropathy: 25 mg three times a day.
- Enalapril: CHF/HTN: 2.5-5 mg daily increased up to 40 mg/day every 1-2 weeks in 2.5 mg intervals. IV : 1.25 mg/dose every 6 hours for up to 36 hours
- Fosinopril: CHF/HTN: 10 mg daily initially, then titrate to effect (max dose 40 mg daily). Usual dose: 20-40 mg daily.
- Lisinopril: HTN: 10 mg daily (no diuretic) or 5 mg daily (if on diuretic) initially. Dose range: 10-40 mg daily. CHF: Initial: 2.5-5 mg once daily; titrate by 10 mg increments every 2 weeks to target of 20-40 mg/day.
- Moexipril: Hypertension: 7.5 mg once daily (not on a diuretic) or 3.75 mg once daily (when combined with a diuretic). Administer 1 hr prior to meal. Maintenance: 7.5-30 mg daily in 1-2 divided doses
- Perindopril Erbumine: HTN: Initial: 4 mg daily; titrate to desired effect every 1-2 weeks to a max dose of 16 mg/day. Usual dose 4-8 mg/day in 2 divided doses. Stable coronary artery disease (CAD): Initial: 4 mg once daily for 2 weeks then increase to 8 mg once daily as tolerated.
- Quinapril: HTN: 10-20 mg daily initially. Initial dose may be reduced to 5 mg daily (if patient on a diuretic). Range:10-40 mg once daily. CHF: 5 mg once or twice daily; titrate to desired effect every week to a dose of 20-40 mg daily in 2 divided doses.
- Ramipril: HTN: 2.5-5 mg once daily (max dose of 20 mg/day). Left ventricular dysfunction (LVD) post-MI: 2.5 mg twice-daily; titrate to 5 mg twice daily as tolerated. Reduced risk of stoke, MI and death Initial: 2.5 mg once daily for 1st week, then 5 mg once daily for weeks 2-4, then titrate to 10 mg once daily as tolerated.
- Trandolapril: CHF/LVD Initial: 1 mg/day, titrate to 4 mg/day as tolerated. HTN: 1 mg/day initially (may use 2 mg/day in black patients); titrate to desired effect in 1 week intervals.
- CrCl 10-50 ml/min: reduce initial recommended dose by 25%, then titrate to effect.
- CrCl <10 ml/min: reduce initial recommended dose by 50%, then titrate to effect.
- No dosage adjustment needed.
- FDA pregnancy risk category D. Avoid in pregnancy.
- ACE inhibitors are teratogenic and have resulted in neonatal morbidity (cardiovascular and CNS) and mortality.
- Concentration in milk is about 1% of serum concentration. Avoid ACE inhibitors during breast feeding.
- Cardiovascular: edema, hypotension (use low dose and titrate slowly in volume contracted patients).
- Drug-related cough (0.5% to 2%)
- Endocrine/metabolic: gynecomastia, hyperkalemia
- Rash
- Renal failure
- Dermatologic: angioedema of face, lips, and throat (0.1%)
- Metallic taste (captopril)
- Hematologic: agranulocytosis (rare), neutropenia (rare)
- Gastrointestinal: intestinal angioedema
- Eosinophilic pneumonitis
- Photosensitivity
- ACE inhibitors may increase the hypoglycemic effects of insulin or other antidiabetic agents
- Potassium-sparing diuretics (e.g spironolactone) and trimethoprim: may increase risk of hyperkalemia.
- Potassium salt: monitor for hyperkalemia with ACE-inhibitor co-administration.
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ARBs (e.g. losartan, telmisartan): may increase risk of renal failure, diarrhea, hypotension, syncope, and hyperkalemia. Monitor renal function closely with ACE inhibitor and ARBs co-administration.
- Lithium: lithium concentration may be increased. Monitor concentrations with ACE inhibitor co-administration.
- Pregabalin: may increase risk of angioedema associated with ACE inhibitors. Use with close monitoring.
- Antacid: may decrease ACE inhibitor absorption. Separate administration time.
- Nephrotic agents (e.g contrast, NSAIDS, aminoglycosides, amphoB): may increase risk of nephrotoxicity. Monitor renal function closely with co-administration.
- Good blood pressure control is advantageous regardless of agent used.
- Our usual practice is to begin an ACE inhibitor or ARB in people with diabetes found to be hypertensive, proteinuric or both. We do not use ACE inhibitors to "protect the kidneys" in all people with diabetes.
- Frequently, other antihypertensives must be added to control blood pressure.
- Numerous trials have shown that ACE inhibitors decrease microalbuminuria and slow progression of diabetic nephropathy in patients with both type 1 and type 2 diabetes (Viberti; Microalbuminaria Captopril Study group; Ravid).
- Captopril is the only FDA-approved ACE inhibitor for diabetic nephropathy although other ACE inhibitors are likely also effective.
- Several studies demonstrated that lisinopril is effective in the reducing urinary albumin excretion in diabetes (Schjoedt). Lisinopril is superior to hydrochlorothiazide in lowering blood pressure, and approximately equal to atenolol and metoprolol in lowering systolic blood pressure, equivalent to atenolol and metoprolol in lowering diastolic blood pressure
- In a well controlled trial of normotensive patients with type 1 diabetes and normoalbuminuria, enalapril 20 mg did not slow progression of nephropathy when compared to placebo, but progression of retinopathy was slowed (Mauer). However, other trials have shown benefit of enalapril in reducing progression of diabetic nephropathy (Ravid).
- Patients with diabetic nephropathy randomized to fosinopril achieved reduced 24 hour urine protein excretion, serum creatinine and BUN. (Huang)
- Trandalopril alone and in combination with verapamil decreased the incidence of microalbuminuria over verapamil alone and placebo in type 2 diabetics with hypertension. (Ruggenenti)
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