The effect of enalapril on baroreceptor mediated reflex function in normotensive subjects.
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Adolescent↗
Biomedical subjects
A A Ajayi
Publications and source records attributed to A A Ajayi.
Age and the pharmacokinetics of angiotensin converting enzyme inhibitors enalapril and enalaprilat.
The pharmacokinetics of angiotension converting enzyme (ACE) inhibitors enalapril (10 mg orally) and its active metabolite, enalaprilat (10 mg intravenously) were studied in nine young healthy volunteers aged 22-30 years and nine sex matched elderly subjects aged 65-73 years. After both drugs, a biexponential curve was fitted to the decline in plasma enalaprilat concentration. Area under the plasma concentration-time curve (AUC) was greater in the elderly for both drugs. Clearance (CL) and clearance/bioavailability (CL/F) were less in the elderly for enalaprilat and enalapril, respectively. There was no difference in F between young (0.62 +/- 0.16) and elderly subjects (0.61 +/- 0.15). Enalaprilat CL and enalapril CL/F were significantly and positively correlated to endogenous creatinine clearance. There was a significant difference in the weight corrected volume of distribution at steady state after enalaprilat between the young and elderly (P less than 0.02). The relationship between plasma enalaprilat concentrations and percentage ACE inhibition, using the Hill equation, showed no difference in the sensitivity to ACE inhibition between the young and the elderly group. The pharmacokinetic differences observed are likely to be related to an age dependent decline in renal function as well as changes in body composition. Kinetic differences partly explain the greater pharmacodynamic response in the elderly.
Adult↗
Age and the pharmacodynamics of angiotensin converting enzyme inhibitors enalapril and enalaprilat.
The effect of age on the pharmacodynamic responses to converting enzyme inhibitors, enalapril and enalaprilat was investigated in nine young (22-30 years) and nine sex-matched elderly (65-73 years), healthy volunteers. The groups differed in baseline blood pressure, young 121/64 mmHg, elderly 142/75 mmHg (P less than 0.01), but not in sodium intake or body weight. Both enalapril and enalprilat produced significant falls in blood pressure in both groups but no increase in heart rate in the supine or erect posture. The blood pressure fall was significantly greater in the elderly on both treatments and in both erect and supine posture. The greater fall in blood pressure in the elderly was associated with a more prolonged inhibition of plasma angiotensin converting enzyme activity. The apparent age-related difference in response appears to be due to the difference in baseline blood pressures between the groups. Further study of the usefulness of chronic dosing with angiotensin converting enzyme inhibitors in hypertension in the elderly is indicated.
Adult↗
The pharmacodynamics and dose-response relationships of the angiotensin converting enzyme inhibitor, cilazapril, in essential hypertension.
In a double-blind, placebo controlled, crossover study 12 patients with essential hypertension received single doses of 5, 10 and 20 mg of cilazapril, a new angiotensin converting enzyme (ACE) inhibitor. All doses similarly and significantly (P less than 0.05) reduced supine and erect blood pressure without increasing heart rate. The hypotensive effect was evident within 1 h, maintained for up to 8 h, with a maximal effect at 6 h. There was no discernible effect on blood pressure at 24 h after dosing. Plasma ACE activity was markedly inhibited to the same extent after all doses, with a peak inhibition of 94-96% at 2-3 h. At 24 h residual inhibition of ACE was 49-54%. Plasma renin activity increased in a dose-dependent manner with a peak at 6 h, and returned to baseline at 24 h. No correlation was found between the reduction in blood pressure and plasma renin activity, either at baseline or following cilazapril. There were no significant changes in plasma noradrenaline and the responses to upright posture and to dynamic exercise were preserved. There was no evidence of impaired exercise performance. Cilazapril is a potent ACE inhibitor with a rapid onset and a prolonged duration of action. These results suggest that peak ACE inhibition is achieved by 5 mg and that lower doses may be useful in clinical practice.
Adult↗
Effect of naloxone on the actions of captopril.
Captopril inhibits the metabolism of endogenous opioids in vitro and potentiates their effects in vivo. We examined the hypothesis that endogenous opioids contribute to the actions of captopril in man. The acute cardiovascular and autonomic effects of oral captopril, intravenous naloxone, and their combination were examined in eight healthy men with normotension in a double-blind, placebo-controlled study of a Latin squares design. Naloxone altered neither blood pressure nor heart rate. There were significant falls in systolic blood pressure during captopril dosing alone, but there was no fall in blood pressure during combination therapy. Heart rates were higher during the combination than during captopril alone. The combination caused sedation, but neither captopril nor naloxone alone had any behavioral effects. Modification of the acute circulatory effects of captopril by naloxone suggests a role for endogenous opioids in the responses to converting enzyme inhibition. The sedation caused by the combination raises the possibility that captopril may exert central nervous actions in man.
Adult↗
Blood pressure distribution of Nigerians in the first two decades of life.
The systolic and diastolic blood pressures of 2301 Nigerian boys and 2017 Nigerian girls were measured. Their ages, which were in the range 1-20 years, heights and weights were also recorded. The relationship between these variables are discussed. Selected percentiles of systolic and diastolic pressures for different ages and weights are given.
Adolescent↗
Acute and chronic effects of the converting enzyme inhibitors enalapril and lisinopril on reflex control of heart rate in normotensive man.
The effects of enalapril maleate and its lysine analogue, lisinopril, on reflex control of heart rate after acute and chronic administration were examined in 10 normotensive males. Both drugs reduced blood pressure without change in heart rate after acute dosing and after seven days. Both drugs impaired the vagally mediated early cardiac acceleration associated with lying down (standing to lying test). A similar effect was observed following edrophonium. After lisinopril bradycardia induced by facial immersion (diving reflex) was significantly attenuated. Edrophonium similarly attenuated the bradycardia. Both these reflexes are parasympathetically mediated. Neither drug altered heart rate or blood pressure changes following Valsalva's manoeuvre and the cold pressor test. Plasma noradrenaline was unchanged. Absence of reflex tachycardia with blood pressure reduction by converting enzyme inhibitors may be related to increased parasympathetic activity either centrally or peripherally without impairment of baroreflexes or sympathetic function.
Adult↗
The effect of captopril on the reflex control heart rate: possible mechanisms.
Angiotensin converting enzyme inhibitors reduce blood pressure without reflex tachycardia, possibly as a result of enhanced hypothesis that this results from the removal of the parasympathetic activity. We examined the vagolytic action of angiotensin II or alternatively by acetylcholinesterase inhibition. Both captopril and [Sar1ala8] angiotensin II, (saralasin), caused modest falls in blood pressure, without increasing heart rate in normotensive subjects. Captopril and saralasin significantly attenuated the vagally mediated heart rate slowing after facial immersion in water. There was a close correlation between the effects produced by captopril and saralasin on the diving reflex. Infusion of subpressor doses of angiotensin II, reversed the hypotensive effect of captopril and returned the bradycardia after facial immersion to placebo level. In vitro neither captopril nor enalapril or lisinopril affected bovine erythrocyte acetylcholinesterase activity. The parasympathetic effect of angiotensin converting enzyme inhibitors appear to reflect a direct consequence of the removal of angiotensin II.
Acetylcholinesterase↗
Pharmacodynamics and population pharmacokinetics of enalapril and lisinopril.
The di-acid metabolite of enalapril, enalaprilat, and its lysine analogue lisinopril are potent inhibitors of angiotensin converting enzyme (ACE); they do not contain sulphydryl groups. Both drugs can be assayed by high pressure liquid chromatography and by radioimmunoassay and plasma ACE inhibition remains stable under normal storage conditions. It is therefore possible to study their pharmacokinetics as well as their pharmacodynamic effects in man. Enalaprilat and lisinopril as well as ACE activity have been measured in blood taken during the course of two studies of the effects of these drugs on blood pressure and autonomic responsiveness. A population pharmacokinetic analysis approach applied to a few concentration-time data points in each of a relatively large number of subjects provided average population parameter estimates of the absorption rate constant, volume of distribution and clearance which correspond closely with the limited published data based on conventional pharmacokinetic approaches. It also provided estimates of pharmacodynamic parameters and the concentration of the drug required to produce a 50% ACE inhibition. Population drug concentration data obtained in the course of early clinical evaluations of new drugs may provide a rational basis for dosage regimens with improved efficacy and, in particular, reduced concentration-related toxic effects.
Adult↗
Prognostic indices for intra-hospital mortality in Nigerian diabetic NIDDM patients. Role of gender and hypertension.
Hypertension and diabetes mellitus are independently associated with a high rate of target organ complications, which is particularly accentuated in the Negroid race. The aims of this study were to evaluate the mortality associated with diabetes mellitus and concurrent hypertension and diabetes mellitus in indigenous Africans, and to identify and assess the factors that are predictive of intra-hospital mortality in Non-Insulin Dependent Diabetes Mellitus (NIDDM) diabetic Nigerians. The subsequent impact of the modification of these risk factors was also evaluated. A prospective study of 51 hypertensive-diabetic (Non-Insulin Dependent Diabetics, NIDDM) Nigerians (32 males, 19 females) over a 15-month period, from 1996 to 1997 was undertaken. The mean admission blood pressures were 170/102+/-35/22 mm Hg, with a body mass index (BMI) of 25.4+/-10.2 kg/m(2). A total of 54 normotensive (BP<130/85 mm Hg)-NIDDM diabetic Nigerians (30 men, 24 women), who were concurrently admitted in the hospital, were compared to the hypertensive-NIDDM. The total mortality of all the NIDDM diabetics, as well as the mortality rates in normotensives and hypertensive-diabetics, were computed. The causes of death and associated complications were noted. Predictive indices of intrahospital mortality were statistically evaluated by comparison of proportions, chi(2) test, Fischer's exact test, logistic regression, and analysis of variance (ANOVA).Over-all mortality rate among all the diabetics (both normotensive and hypertensive) was 26.6% (28/105), which was significantly higher than the crude death rate on the Internal Medicine service of 17.8% (P=0.006) or the non-obstetric crude death rate in the hospital of 10.96% (P=0.001) Among the hypertensive-NIDDM patients (n=51) the mortality rate was 31.4% (16 deaths/51 patients). This was slightly higher than the value of 22.2% (12 deaths/54 patients) seen in normotensive -NIDDM patients. The mortality rate among the male diabetics (23/63 patients) 46.6% was significantly higher than female mortality rate of 11.6% (5/43). The 95% Confidence interval for the difference in mortality rates being 16.9% to 53.3% (P<0.0001, z=3.57). The impact of gender remained significant by the chi(2) test, chi(2)=7.17, P=0.007. 50% of the deaths in hypertensive-diabetics had associated stroke (8/16), while none of the 12 deaths among the normotensive-diabetics was stroke-related (P=0.008, Fisher's exact test). The case fatality rate for stroke in hypertensive-NIDDM men (7/7.9) was significantly greater than in hypertensive-NIDDM women (1.0/7) (P=0.04,by Fisher's exact test). Male gender, presence of Hyperosmolar Non-Ketotic Coma (HONK) (P<0. 05), associated stroke (P<0.01) and a Glasgow coma < or =10 (P<0.01) were found to be poor prognostic indices for mortality in hypertensive-NIDDM. Aggressive anti-platelet, (aspirin) anti-hypertensive, and strict glycemic control, instituted early and intensively, especially in male hypertensive-NIDDM Nigerians have resulted in reduction in the mortality rates from 26.6% in 1997 to 12.6% in 1999 [P=0.05, 95% CI -26.9% to -1.3%]. The prognosis in 1999 of hospitalized African diabetics is still dismal. Hypertensive-NIDDM represents a higher risk group for intra-hospital mortality in black Africans. Male patients appear to have significantly (P<0.001) enhanced risk, especially with thrombotic/stroke-related deaths (P<0.01). However, intervention measures can reduce the mortality rate considerably, even in developing countries. The mechanisms of the apparent male mortality excess require elucidation.
Adult↗
Muscarinic blockade with oral hyoscine palliates angiotensin converting enzyme inhibitor induced cough.
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Administration, Oral↗
Chronotropic dose response of atropine in Nigerians with congestive heart failure: assessment of ethnic variation and reversibility of parasympathetic dysfunction.
Both ethnicity and disease states may influence cardiac parasympathetic tone. We evaluated the cardiac vagal activity in 9 Nigerians aged 57(11) with congestive heart failure, and 9 age- and sex-matched healthy controls aged 51(11) years, using a cumulative low dose atropine response curve. All subjects demonstrated bradycardia at low doses (100 microg-400 microg) and tachycardia at higher doses (600 microg-1,000 microg). However, both the bradycardic and the tachycardic responses were attenuated in heart failure patients compared to controls: bradycardia -1.1(1.5) beats/min in heart failure patients vs -7.1(2.2) beats/min in controls (P<.01) and tachycardia +4(1.5) beats/min in heart failure patients vs +14.3(3) beats/min in healthy controls (P<.01). EC50 values for brachycardia and tachycardia calculated from the dose response curves were significantly higher in healthy controls compared to heart failure patients, for bradycardia 69(39) microg versus 11(1.6) microg (P<.01) and tachycardia 682(61) microg vs 254(84) microg (P<.01). Treatment of heart failure for 4 weeks with furosemide, digoxin and angiotensin converting enzyme inhibitor (enalapril) caused a significant increase in the magnitude of both the bradycardic responses from -1.1(1.5) beats/min to -4.4(0.9) beats/min after treatment, and tachycardic responses from +4(1.5) beats/min to +10.(2.3) beats/min 4 weeks after treatment (P<.05). After 4 weeks of treatment, EC50 was also increased significantly toward normal values. For tachycardia, the values were 254(88) microg before treatment vs 529(78) microg after treatment (P<.05); and for bradycardia, the values were 2.5(1.6) microg before treatment vs 30(13) microg after treatment (P<.05). These findings demonstrate the early bradycardic effect of atropine in Black Africans (both healthy controls and heart failure patients), contradicting earlier reports of its absence in the negroid race. This confirms the reduction in cardiac parasympathetic responsiveness (both maximal heart rate change and EC50) in hypertensive heart failure using a pharmacological assay. It demonstrates the augmentation and amelioration of cardiac vagal tone with enalapril-dixogin-diuretic therapy in non-ischemic heart failure, and the sequential utility of the low dose atropine-chronotropic response in assessing cardiac parasympathetic activity.
Adult↗
Angiotensin converting enzyme inhibitor induced cough in Nigerians.
A persistent dry cough is the commonest class of adverse reaction to Angiotensin converting enzyme inhibitors (ACE-I). This ACE-I induced cough appears to exhibit interracial differences being commoner in Chinese subjects as compared to Caucasians. We conducted a cross sectional study of one hundred (100) patients (63 males and 37 females) on ACE-I to determine the prevalence of ACE-induced cough in Nigerians, a Negroid population. Twenty seven patients (27%) had ACE-induced cough and four (4%) had withdrawal of ACE-I therapy on account of cough. The prevalence of ACE-I induced cough was significantly higher amongst females (43%) as compared to males (17%) p < 0.01. The biological basis for the apparent racial and gender differences in ACE-I induced cough requires further study.
Aged↗
Evidence of in vivo platelet activation during heparin anticoagulation in pregnancy for prophlaxis or treatment of thromboembolism.
Conventional unfractionated heparin substantially enhances spontaneous platelet aggregation in pregnancy in vitro, and may cause platelet activation in healthy volunteers in vivo. It is unknown, however, whether therapeutically administered heparin affects platelet behavior during pregnancy. In a parallel group ex vivo study, 8 third trimester pregnant patients requiring anticoagulation with heparin exhibited a trend to a greater spontaneous platelet aggregation, in comparison to 11 age-matched healthy third trimester pregnant controls. This is consistent with heparin-induced platelet activation in vivo during therapeutic anticoagulation. Peak aggregation in the heparin-treated group was 48 +/- 4% compared to 37 +/- 5% in the healthy controls, (P = 0.086 ANOVA): and significant time treatment interaction (P = 0.03 ANOVA). There was also a weak positive correlation (r = 0.54) between the peak % spontaneous platelet aggregation and the activated partial thromboplastin time ratio during heparin administration.
Adult↗
Adolescent sexuality and fertility in Kenya: a survey of knowledge, perceptions, and practices.
This article presents findings from a survey conducted in Kenya in 1985 of the reproductive health knowledge, attitudes, and practices among more than 3,000 unmarried Kenyan youth, students and nonstudents, between the ages of 12 and 19. The survey was designed to elicit information that would be useful in gauging the kinds of problems Kenyan adolescents face in order to design programs that meet their needs. The study shows that although a solid majority of adolescents appear to have received information on reproductive health, the quality of the information is generally low. Fewer than 8 percent could correctly identify the fertile period in a woman's menstrual cycle. A substantial proportion of the population surveyed, more than 50 percent, is sexually active, having initiated intercourse some time between 13 and 14 years of age, on average. In spite of a general disapproval of premarital sex (but approval of the use of contraceptives among the sexually active), most of the sexually active population--89 percent--have never used contraceptives. The many contradictions between attitudes and practices pose serious questions and demonstrate the need to reexamine the programs (and policies) that provide access to reproductive health services to adolescents in Kenya.
Abortion, Induced↗