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Biomedical subjects

J G Kelly

Publications and source records attributed to J G Kelly.

At least 37 records · Page 2Linked to original sources
PubMed1989

Lisinopril population pharmacokinetics in elderly and renal disease patients with hypertension.

1. The population pharmacokinetics of lisinopril were investigated using data collected from two multicentre trials of lisinopril in the treatment of hypertension in elderly patients (n = 40) and patients with renal disease (n = 20). 2. Lisinopril was started at doses of 2.5-5 mg daily and increased at 2-4 weekly intervals as required for control of blood pressure. Steady-state concentration-time profiles were measured after at least 2 weeks at a constant dose. 3. All concentration-time data were analysed simultaneously using the program NONMEM and the influence of clinical factors on clearance/F and volume of distribution/F was tested. 4. Clearance was significantly influenced by creatinine concentration, age, weight and cardiac failure. No clinical features tested were found to influence volume of distribution. 5. The influence of renal function and cardiac failure on lisinopril clearance has been confirmed using a population pharmacokinetic analysis technique.

Age Factors↗
PubMed1988

Antihypertensive and renal effects of lisinopril in older patients with hypertension.

The antihypertensive efficacy and safety of lisinopril were assessed in 60 older patients with a mean age of 75 years (range, 65 to 85 years) in a 12-week open study. Mean ( +/- SEM) blood pressure while sitting was reduced from 190/106 +/- 3.3/1.8 mm Hg at entry to 162/89 +/- 3.2/1.6 mm Hg after 12 weeks of treatment (p less than 0.001). There was no significant alteration in heart rate, and postural hypotension did not occur. Mean glomerular filtration rate at entry was 61.6 +/- 3.4 ml/minute and was unchanged after 12 weeks of therapy at 62.2 +/- 3.0 ml/minute. Fourteen patients continued to receive lisinopril for a period of one year. Blood pressure remained controlled throughout and heart rate remained unchanged. There was a significant reduction in mean arterial pressure from 128.8 +/- 1.9 mm Hg to 105.1 +/- 1.5 mm Hg (p less than 0.001). Biochemical parameters remained unaltered. There was a significant increase in renal blood flow (p less than 0.025) and a corresponding reduction in renovascular resistance (p less than 0.001) following long-term therapy with lisinopril. Thus, lisinopril was generally well-tolerated and highly effective in lowering blood pressure in older hypertensive patients, whereas at the same time renal function was not adversely changed.

Aged↗
PubMed1988

Pharmacokinetics of amlodipine in renal impairment.

The pharmacokinetics of amlodipine was studied in 27 subjects with renal function ranging from normal to dialysis-dependent. Amlodipine (as a single 5-mg capsule) was administered once daily for 14 days and its plasma concentrations were measured by gas chromatography during and after treatment. Renal impairment had little or no effect on the pharmacokinetics of amlodipine. The elimination half-life was of the order of 50 h, similar to previously observed values, and did not vary with differences in renal function. Steady-state predose concentrations were observed after the ninth dose. Accumulation of amlodipine to steady-state levels was not significantly different from that expected on theoretical grounds and did not significantly change with renal function. These results suggest that once-daily administration of amlodipine is suitable for all degrees of renal function and that dosage adjustment is not necessary in renal impairment.

Adult↗
PubMed1988

Pharmacokinetics of lisinopril, enalapril and enalaprilat in renal failure: effects of haemodialysis.

1. Lisinopril and enalapril were administered as 2.5 mg single doses and as eight single daily 2.5 mg doses to separate groups of six patients with chronic renal failure. Patients were receiving regular haemodialysis. 2. In the absence of haemodialysis, the decline in plasma concentrations of lisinopril and enalaprilat was extremely slow and plasma concentrations were generally high. 3. Haemodialysis had large effects on plasma concentrations of lisinopril and enalaprilat. A 4 h period reduced plasma concentrations of both drugs by around one-half and often by significantly more than this. Even 1 or 2 h of haemodialysis had significant effects. 4. Haemodialysis plasma clearance was similar for both drugs with mean values of the order of 40 ml min-1. Clearance did not markedly differ when measured after 1, 2 or 4 h of haemodialysis or after single or multiple doses of lisinopril or enalapril. 5. The design of dosage regimens of both lisinopril and enalapril for patients with severe renal impairment or chronic renal failure should take into consideration the use and effects of haemodialysis.

Adult↗
PubMed1988

Chronic dose urinary and serum pharmacokinetics of norfloxacin in the elderly.

1. Norfloxacin was administered as two daily 400 mg oral doses to eight elderly patients requiring treatment for urinary tract infections. Blood specimens were obtained for pharmacokinetic profiles following the first and fifteenth doses. Further specimens were obtained before each morning's dose of norfloxacin. Specimens of urine were obtained to ascertain if adequate antimicrobial concentrations were reached in these patients with diminished renal function. 2. Norfloxacin half-life was consistent with that expected in mild renal impairment and was not different between the first and fifteenth doses. Based on ratios of AUC values, accumulation is probably related to renal function, being greatest for creatinine clearance values below 30 ml min-1. 3. On the great majority of occasions, the urinary concentrations of norfloxacin exceeded 20 micrograms ml-1. On days 2-7, the mean percentage 12 h renal elimination of norfloxacin was 18.6 +/- 1.47 (mean of 82 separate observations). Norfloxacin 400 mg twice daily was well tolerated in this group of elderly patients and produced adequate antimicrobial concentrations in urine.

Aged↗
PubMed1988

A study of the potential pharmacokinetic interaction of lisinopril and digoxin in normal volunteers.

1. The pharmacokinetics of single oral doses of 20 mg lisinopril and 0.25 mg digoxin, given alone and together, have been studied in 12 normal young male volunteers. 2. Peak serum conc of lisinopril occurred at 6 to 8 h and were slightly higher during combined treatment. Subsequent elimination proceeded moderately rapidly in both cases, concn declining to approx. 25% of peak values in 24 h. The AUC of lisinopril was similarly slightly higher during combined treatment. 3. After lisinopril alone, urinary elimination of unchanged lisinopril was 13% dose in 72 h, and after combined therapy was 17% dose. 4. Although there were no statistically significant differences in lisinopril pharmacokinetics during single or combined treatment, serum and urinary parameters suggest that bioavailability may be enhanced slightly during combined treatment. 5. Plasma concentrations of digoxin were slightly lower and urinary excretion slightly higher during combined treatment, the mean renal clearance being 20% higher.

Adult↗
PubMed1988

Staff stress in critical care units.

Research on stress experienced by staff in critical care units has predominantly focused on the nurses; however, a small number of investigations have centred on intensivist neonatologists and paediatricians. Australian studies which have highlighted the major stressors encountered by critical care staff are reviewed. Research is reported which suggests that job satisfaction is diminished for staff working within highly stressful critical care units. Implications are discussed in order to focus attention upon the effects of high dependency stressful work environments.

Australia↗
PubMed1988

Adrenoceptor status and cardiovascular function in ageing.

Adrenoceptor function is an important determinant of the physiological control of the circulation and of the response to drugs acting via the sympathetic nervous system and on the vasculature. There is little consistent evidence for an age-dependent change in alpha-adrenoceptor function though the response to various vasoconstrictor agents including alpha 1 agonists has been shown to change with ageing. These changes seem to reflect structural or functional factors and are not specific for receptor types. In the case of beta-adrenoceptor mediated responses there is evidence for both a decrease in response as well as age-related changes in the functioning of various components of the beta-adrenoceptor system, including receptor affinity, which is decreased. It may well be that decreased beta-adrenoceptor function with ageing contributes to altered cardiovascular control and to decreased efficacy of beta-adrenoceptor blocking drugs in elderly hypertensives.

Age Factors↗
PubMed1987

The effect of chronic captopril therapy on platelet angiotensin II receptor density and vascular responsiveness to angiotensin II infusion.

The density of angiotensin II (Ang II) receptors on the platelet and the vascular responsiveness to infused angiotensin II before and after two weeks of captopril therapy were examined in ten healthy male volunteers. There was a significant increase in blood flow to the forearm, but no significant changes in either the density of angiotensin II receptors or the pressor response to infused angiotensin II following captopril therapy. The study demonstrates that long term reduction of angiotensin II formation by captopril in man does not increase the responsiveness of the receptors to infused angiotensin, nor results in an "up regulation" of the angiotensin receptors. It also provides further evidence that some of the long term vasodilator effects of captopril may be mediated by mechanisms other than inhibition of angiotensin I (Ang I) converting enzyme.

Adolescent↗
PubMed1986

Pharmacokinetics of enalapril in normal subjects and patients with renal impairment.

The pharmacokinetics of enalaprilat were studied after administration of single and multiple doses of enalapril maleate to people with normal and impaired renal function. Renal impairment was associated with higher serum concentrations of enalaprilat, longer times to peak concentrations, slower decline of serum concentrations and with reduced urinary elimination. Urinary elimination of enalaprilat was closely related to renal function. In patients with severe renal impairment (GFR values below 30 ml min-1 1.73 m-2) significantly smaller doses of enalapril maleate will be required than in patients with normal or less severely impaired renal function.

Adult↗
PubMed1985

Choice of selective versus nonselective beta blockers: implications for exercise training.

Administration of beta blockers decreases tachycardia during exercise. In this regard, the effects of cardioselective drugs are similar to those of noncardioselective drugs. Beta blockers with partial agonist activity, however, may produce a lesser decrease in tachycardia during exercise. Cardioselective beta blockers have significantly less effect than noncardioselective drugs on isoproterenol-induced tachycardia. This may result from 2 factors: the failure of cardioselective drugs to block a beta 2 receptor-mediated vasodilator reflex tachycardia and their failure to block cardiac chronotropic beta 2 receptors. Exercise increases plasma catecholamine concentrations and the increases are larger in the presence of beta blockers. Cardioselective beta blockers produce larger increases. There is evidence for attenuation of exercise conditioning by beta blockers and this effect is probably shared by cardioselective and noncardioselective drugs. Beta blockers produce regulatory increases in beta receptor density, and physical training may do the opposite. The interaction between these 2 processes remains to be defined.

Adrenergic beta-Antagonists↗
PubMed1985

Stress, coping behaviors, and recommendations for intensive care and medical surgical ward registered nurses.

Forty one intensive care unit and 61 medical surgical ward registered nurses from two large urban teaching hospitals completed a stress questionnaire to examine stress factors, coping behaviors, and recommendations for alleviating stress within the work environment. Stress variables were grouped into five clusters: patient-related, environmental, management-related, interpersonal, and knowledge and skills. Multivariate analysis of variance demonstrated a significant main effect, with the ward nurses perceiving environmental factors as more stressful. Stress factors tend to be related to the overall hospital environment, especially in relation to specific work areas within the institutions.

Adaptation, Psychological↗
PubMed1985

Protein binding and disposition of lignocaine in the elderly.

Single dose studies were performed in six young and six elderly nonsmokers using lignocaine as a model drug with high intrinsic clearance. Subjects received lignocaine 250 mg orally and 50 mg intravenously in random order and drug concentrations in blood and plasma were measured for up to 8 h after dose. Protein binding was estimated at 37 degrees C by equilibrium dialysis. Indocyanine green kinetics were also calculated in each individual following 0.15 mg/kg intravenously. Bioavailability of lignocaine was greater in the elderly but there was no apparent difference in the rate of absorption. Intrinsic clearance of lignocaine was lower in the aged. Elimination half-life was longer in the elderly but there was no significant difference in apparent volume of distribution or systemic clearance of lignocaine. Plasma clearance of indocyanine green showed no correlation with systemic lignocaine clearance and was lower in the aged subjects. Blood/plasma lignocaine ratio was less than unity in both groups. Binding of lignocaine to plasma proteins showed concentration-dependence and was higher in the geriatric group. Maximum binding capacity of lignocaine was greater in the elderly but the binding affinity did not significantly change with age. Greater oral bioavailability of drugs like lignocaine may produce higher plasma concentrations in the elderly. Unlike indocyanine green, the systemic clearance of lignocaine was unaltered by age in this group of non-smokers. The protein-binding of lignocaine, like many other basic drugs, is increased in elderly subjects.

Adult↗
PubMed1985

Effects of ranitidine on the disposition of metoprolol.

The effects of ranitidine on the pharmacokinetics of metoprolol were examined in two studies. In the first study, pharmacokinetics of single doses of metoprolol were examined in six subjects before, during and after ranitidine administration for 1 week. Peak concentrations of metoprolol were increased on ranitidine but its half-life and clearance were unaltered. In the second study, 12 subjects received metoprolol twice daily for 1 week; once with ranitidine and once with placebo. Ranitidine had no effects on the chronic-dose pharmacokinetics or pharmacodynamics of metoprolol. The chronic dose study suggests no inhibition of the metabolism of metoprolol by ranitidine. The single dose study suggests, however, that some interaction of an as yet unknown nature, cannot be excluded.

Adult↗
PubMed1985

Pharmacokinetics and haemodynamic effects of tocainide in patients with acute myocardial infarction complicated by left ventricular failure.

The pharmacokinetics and haemodynamic effects of tocainide, an orally active structural analogue of lignocaine, were studied in patients with acute myocardial infarction complicated by left ventricular failure. Fourteen patients (mean age 65 years) with acute myocardial infarction complicated by mild left ventricular failure were studied, following a single dose of tocainide (250 mg) by intravenous infusion, over 30 min. Heart rate, systemic arterial pressure, pulmonary artery pressure and cardiac output were monitored. Plasma tocainide levels were estimated by gas chromatography. The mean plasma level of tocainide achieved was 2.95 micrograms/ml (15.37 mmol/l). The mean plasma half-life was 15.6 h. The mean cardiac index was reduced 5 min after completion of the infusion, from 2.24 1 min-1 m-2 (+/- 0.40) to 2.07 1 min-1 m-2 (+/- 0.29) (P less than 0.01). At 90 min the cardiac index had returned to pre-treatment levels. Small changes were seen in the heart rate, arterial blood pressure and the pulmonary artery pressure but these changes were not statistically significant. The pharmacokinetics of tocainide were not significantly altered in patients with acute myocardial infarction complicated by mild left ventricular failure.

Aged↗