Captopril dosing

Oral captopril doses of 25 to 50 mg may be given at 1- to 2-hour intervals. The onset of action is 15 to 30 minutes. 

Noncompliance with drug therapy or skipping captopril doses may cause severe, rebound hypertension... 

Hypotension is more common in patients with heart failure who are receiving large doses of diuretics. In a study in 124 patients with severe heart failure, all receiving furosemide (mean dose 170 mg daily range 80 to 500 mg daily) and 90 also receiving the potassium-sparing diuretic spironolactone, the addition of captopril caused transient symptomatic hypotension in 44% of subjects. The captopril dose had to be reduced, and in 8 patients it was later discontinued. In addition, four patients developed symptomatic hypotension after 1 to 2 months of treatment, and captopril was also discontinued in these patients. ... 

Captopril 6.25 to 12.5 mg initially target dose 50 mgtwoorthree times daily. 

All 10 ACE inhibitors available in the United States can be dosed once daily for hypertension except captopril, which is usually dosed two or three times daily. The absorption of captopril (but not enalapril or lisinopril) is reduced by 30% to 40% when given with food. 

Autoantibodies to red blood cells and autoimmune hemolytic anemia have been observed in patients treated with numerous drugs, including procainamide, chlor-propaminde, captopril, cefalexin, penicillin, and methyldopa (Logue et al., 1970 Kleinman et al., 1984). Hydralazine- and procainamide-induced autoantibodies may also result in SLE. Approximately 20% of patients administered methyldopa for several weeks for the treatment of essential hypertension developed a dose-related titer and incidence of autoantibodies to erythrocytes, 1% of which presented with hemolytic anemia. Methlydopa does not appear to act as a hapten but appears to act by modifying erythrocyte surface antigens. IgG autoantibodies then develop against the modified erythrocytes. 

Captopril-lysozyme did not significantly affect systemic blood pressure whereas an equimolar dose of captopril alone decreased blood pressure significantly. Whereas free captopril (5 mg kg ) completely prevented an angiotensin-I-induced blood pressure increase, an equimolar amount of captopril-lysozyme did not. However, in line with the direct ACE activity measurements in renal tissue and plasma, in captopril-lysozyme-treated rats the an-giotensin-I-induced blood pressure increase was lower than in untreated rats, suggesting that systemic activity was not fully prevented. 

Accelerated or malignant hypertension Promptly initiate captopril at 25 mg 2 or 3 times daily under close supervision. Increase dose every 24 hours or less until a satisfactory response is obtained or the maximum dose is reached. 

Heart failure - Usual initial dosage is 25 mg 3 times daily. After 50 mg 3 times daily is reached, delay further dosage increases, where possible, for at least 2 weeks to determine if a satisfactory response occurs. Most patients have had a satisfactory clinical improvement at 50 or 100 mg 3 times daily. Do not exceed a daily dose of 450 mg. Captopril should generally be used in conjunction with a diuretic and digitalis. 

Captopril s pharmacokinetic parameters and dosing recommendations are set forth in Table 11-2. Peak concentrations of enalaprilat, the active metabolite of enalapril, occur 3-4 hours after dosing with enalapril. The half-life of enalaprilat is about 11 hours. Typical doses of enalapril are 10-20 mg once or twice daily. Lisinopril has a half-life of 12 hours. Doses of 10-80 mg once daily are effective in most patients. All of the ACE inhibitors except fosinopril and moexipril are eliminated primarily by the kidneys doses of these drugs should be reduced in patients with renal insufficiency. 

ACE inhibitors are contraindicated during the second and third trimesters of pregnancy because of the risk of fetal hypotension, anuria, and renal failure, sometimes associated with fetal malformations or death. Recent evidence also implicates first-trimester exposure to ACE inhibitors in increased teratogenic risk. Captopril, particularly when given in high doses to patients with renal insufficiency, may cause neutropenia or proteinuria. Minor toxic effects seen more typically include altered sense of taste, allergic skin rashes, and drug fever, which may occur in up to 10% of patients. 

FIGURE 4.3 Antihypertensive activities of ACE-inhibitory peptides after single oral administration in SHRs. SHRs were administered captopril (O), the ACE-inhibitory peptide from rotifer ( ) at a dose of 50mg/kg. Changes in systolic blood pressure were expressed as mean SE [n—5). Statistical analyses were done by Student t-test (P<0.05) (Skeggs et at., 1957). 

Iodinated radiographic contrast media can cause acute renal insufficiency, perhaps as a result of reduced renal blood flow, an intrarenal osmotic effect, or direct tubular toxicity (58). Diuretics, calcium channel blockers, adenosine receptor antagonists, acetylcysteine, low-dose dopamine, the dopamine Di receptor agonist fenoldopam, endothelin receptor antagonists, and captopril have all been used to prevent contrast nephropathy. 

Captopril s pharmacokinetic parameters and dosing recommendations are set forth in Table 11-1. 

The half-life of captopril is short (<3 hours). A drug with a short half-life requires more frequent dosing to maintain an effective concentration in the body. This can result in inadvertently missed doses. More important than the short half-life, some patients taking captopril report rashes and a lack of taste sensation (dysgeusia). 

In the high-renin Goldblatt two-kidney, one-clip renal hypertensive rat, immediate pressure lowering was observed with orally administered captopril (30 mg/kg), and an antihypertensive effect could be maintained for at least 10 months. Spontaneously hypertensive rats, which are considered to be a model of essential hypertension in humans, also responded to oral captopril, but a dose of 100 mg/kg was required. As expected in both models of hypertension, the addition of diuretics enhanced the antihypertensive activity of captopril (105). 

Clinical testing began in 1976 in a study in normal volunteers, in which the pressor activity of intravenous angiotensin I was inhibited by increasing oral doses of captopril ranging from 1 to 20 mg (106). The extensive clinical studies that led to its approvals have been reviewed (98,107-111). Captopril was first approved in 1981 for use in hypertensive patients poorly responsive to multidrug therapy. It received FDA approval in 1982 for heart failure and in 1985 for general use in hypertension (101). For... 

With the data included in the overview of Garg et al. (316), it is possible to calculate that 18 patients need to be treated for 90 days to avoid one death or one hospitalization for congestive heart failure (95% confidence interval [Cl] 16-23). This meta-analysis includes 32 trials with the ACE inhibitors captopril, enalapril, lisinopril, quinapril, ramipril, and perindopril. It is likely that high doses (for instance, lisinopril 35 mg daily) are more effective than low doses (lisinopril 5 mg daily) (302). Treating 30 patients for 4 years with a high dose of lisinopril (95% Cl 16-509) will avoid one hospitalization for cardiovascular reasons or one death in comparison with a low dose, without increasing the number of adverse effects requiring withdrawal from treatment. 

Neutropenia is rare, and occurs more frequently in patients with renal or collagen vascular disease. These side effects are dose-related and might derive from toxic effects caused by the sulfhydryl group (captopril). 

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