captopril (Rx)

>10%

Hyperkalemia (1-11%)

1-10%

Hypersensitivity rxns (4-7%)

Skin rash (4-7%)

Dysgeusia (2-4%)

Hypotension (1-2.5%)

Pruritus (2%)

Cough (0.5-2%)

Chest pain (1%)

Palpitations (1%)

Proteinuria (1%)

Tachycardia (1%)

Frequency Not Defined

Cardiac arrest

Orthostatic hypotension

Ataxia

Confusion

Depression

Somnolence

Angioedema

Photosensitivity

Neutropenia

ARF if renal artery stenosis

Renal impairment

Impotence

Contraindications

Hypersensitivity to ACE inhibitors

Anuria

History of ACEI-induced angioedema

Hereditary or idiopathic angioedema

Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan

Bilateral renal artery stenosis

Do not coadminister with aliskiren in patients with diabetes mellitus or with renal impairment (ie, GFR <60 mL/min/1.73 m²)

Cautions

Aortic stenosis/hypertrophic cardiomyopathy, hypotension, biliary cirrhosis or biliary obstruction, myelosuppression, electrolyte imbalance, hyperuricemia or gout, SLE, hepatic or renal impairment

Avoid concomitant use with lithium

Less effective in African-Americans

Excessive hypotension if concomitant diuretics or volume-depleted; start with 6.25 mg q8hr

Risk of hyperkalemia, especially with K+ sparing diuretics

Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure) compared to monotherapy

Blood levels don't correlate with BP response

Food decreases absorption

ACE inhibition also causes increased bradykinin levels which putatively mediates angioedema

Coadministration with mTOR inhibitors (eg, temsirolimus, everolimus, sirolimus) may increase risk for angioedema

Intestinal angioedema, that presented with abdominal pain, reported in patients treated with ACE inhibitors

Neutropenia (<1000/mm³ with myeloid hypoplasia reported with captopril; risk is dependent on clinical status of patient

Causes false positive urine acetone

Pregnancy Category: C; D in 2nd & 3rd trimesters

Discontinue as soon as pregnancy detected; during the second and third trimesters of pregnancy, drugs that act directly on the renin-angiotensin have been associated with fetal injury that includes hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death

Lactation: enters breast milk/not recommended (AAP states compatible with nursing)

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Angiotensin converting enzyme (ACE) inhibitors dilate arteries and veins by competitively inhibiting the conversion of angiotensin I to angiotensin II (a potent endogenous vasoconstrictor) and by inhibiting bradykinin metabolism; these actions result in preload and afterload reductions on the heart

ACE inhibitors also promote sodium and water excretion by inhibiting angiotensin-II induced aldosterone secretion; elevation in potassium may also be observed

ACE inhibitors also elicit renoprotective effects through vasodilation of renal arterioles

ACE inhibitors reduce cardiac and vascular remodeling associated with chronic hypertension, heart failure, and myocardial infarction

Pharmacokinetics

Half-life: 1.9 hr (healthy); 2.06 (heart failure); 20-40 hr (anuria); significantly increase in CrCl <20 mL/min

Onset: PO: initial response: 15-30 min; peak response: 60-90 min

Duration: PO (multiple dose): 8-12 hr

Peak plasma time: PO: 0.5-1.5 hr

Therapeutic range: 0.05-0.5 mcg/mL

Bioavailability: 70-75%

Protein bound: 25-30%

Vd: 0.7 L/kg

Metabolism: liver (50%)

Metabolites: captopril-cysteine disulfide (inactive)

Total body clearance: 0.8 L/kg/hr

Renal clearance: 0.4 L/kg/hr

Excretion: mainly urine (95%)

Dialyzable: Yes (HD)