Drugs online research references
Arq Bras Cardiol. 1999 Oct;73(4):359-72.
Effects of lisinopril on experimental ischemia in rats. Influence of infarct size.
Zornoff LA, Matsubara BB, Matsubara LS, Paiva SA, Tornero MT, Spadaro J.
Universidade Estadual Paulista, Botucatu, SP, 18618-000, Brazil.
OBJECTIVE - Angiotensin-converting enzyme inhibitors (ACEIs) have gained importance in preventing or attenuating the process of ventricular remodeling after myocardial infarction. The significance of infarct size in regard to the response to ACEIs, however, is controversial. This study aimed to analyze the effects of lisinopril on mortality rate, cardiac function, degree of cardiac hypertrophy and fibrosis in rats with different infarct sizes. METHODS - Lisinopril (20 mg/kg/day) dissolved in drinking water was administered to rats immediately after coronary artery occlusion. After being sacrificed, the infarcted animals were divided into two groups: one group of animals with small infarcts (< 40% of the left ventricle) and another group of animals with large infarcts (> 40% of the left ventricle). RESULTS - The mortality rate was 31.7% in treated rats and 47% in the untreated rats. There was no statistical difference between the groups with small and large infarcts in regard to myocardial concentration of hydroxyproline. In small infarcts, the treatment attenuated the heart dysfunction characterized by lower levels of blood pressure and lower values of the first derivative of pressure and of the negative derivative of pressure. The degree of hypertrophy was also attenuated in small infarcts. In regard to large infarcts, no differences between the groups were observed. CONCLUSION - Treatment with the ACEIs had no effect on mortality rate and on the amount of fibrosis. The protective effect of lisinopril on heart function and on the degree of hypertrophy could only be detected in small infarcts
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Clin Ther. 1993 Mar-Apr;15(2):407-22.
Lisinopril in the treatment of hypertension: a Canadian postmarketing surveillance study.
Huckell VF, Belanger LG, Kazimirski M, Subramanian T, Cox AJ.
University of British Columbia, Vancouver, Canada.
A postmarketing surveillance study in 2273 Canadian office practices provided the largest body of clinical experience to date with the angiotensin-converting enzyme (ACE) inhibitor lisinopril in the treatment of mild to moderate essential hypertension. The principal emphasis in this uncontrolled study was safety, assessed in 10,289 patients. Patients with a diastolic blood pressure > 90 mmHg were considered for the study. Both previously untreated patients and those who were experiencing adverse effects from their current antihypertensive regimen were included. Lisinopril was begun at a dose of 10 mg/day. Subsequent dose adjustments, to a maximum of 40 mg/day, were made to achieve optimal blood pressure control (diastolic blood pressure < or = 90 mmHg or > or = 10 mmHg below baseline for > or = 4 weeks at the same dose). Therapy was continued for a minimum of 4 weeks to a maximum of 12 weeks, with patients examined every 2 weeks. The frequencies of adverse effects and laboratory abnormalities were analyzed in all treated patients. All 10,289 patients enrolled were considered in the analysis of safety. One or more adverse effects were reported for 1593 (15.5%) patients, and 802 (7.8%) withdrew from the study because of adverse effects. The most frequent adverse effects were cough (4.0%), dizziness (2.3%), headache (2.1%), asthenia (1.7%), and nausea (1.0%). The physicians' global assessment rated overall tolerability as very good or good for 77.1% of the patients. Antihypertensive effect was evaluated in 5886 patients who met the criteria for efficacy analysis. The criterion response was attained in 5141 (87.3%) patients, with 68.6% responding to 10 mg/day of lisinopril, 26.3% to 20 mg/day, and 3.2% to 40 mg/day (the other 1.9% responded at nonstandard doses). Lisinopril was safe and well-tolerated. Except for cough, class effects of ACE inhibitors were rarely encountered. The results of the efficacy analysis confirm the established efficacy of lisinopril in patients with mild to moderate essential hypertension.
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Kidney Int. 1993 Jun;43(6):1210-8.
Long-term effects of antihypertensive regimens on renal hemodynamics and proteinuria.
Brown SA, Walton CL, Crawford P, Bakris GL.
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens.
The long-term effects of different antihypertensive regimens were studied in uninephrectomized beagles with alloxan-induced diabetes mellitus. Mean arterial pressure (MAP) was elevated (P < 0.05) in untreated diabetic dogs. Treatment of diabetic dogs with an angiotensin converting enzyme inhibitor (ACEI; lisinopril), a calcium antagonist (CA;TA-3090), or both lowered MAP. At one year, the RBF, GFR, and SNGFR were similarly elevated (P < 0.05) in all groups of diabetic dogs. The increase in SNGFR present in untreated diabetic dogs was primarily attributable to an increased (P < 0.05) glomerular capillary pressure (PGC). Treatment with lisinopril lowered the PGC to a mean value that was indistinguishable from that for nondiabetic dogs. In contrast, diabetic dogs treated with TA-3090 had an elevated PGC. While untreated diabetic dogs exhibited marked increases in glomerular volume (P < 0.05 vs. nondiabetic dogs), treatment with lisinopril and TA-3090, either alone or in combination, blunted the extent of glomerular hypertrophy observed in diabetic dogs (P < 0.05 vs. untreated diabetic dogs). Proteinuria was similarly reduced (P < 0.05 vs. untreated diabetic dogs) in dogs treated with lisinopril and TA-3090. Combination therapy of diabetic dogs produced a further significant (P < 0.05) decrement in proteinuria. We conclude that although treatment of diabetic dogs with either lisinopril or TA-3090 results in differential effects on PGC; each produces a similar decrement in proteinuria. Further, combination therapy has a greater effect on proteinuria than either agent alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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