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Biomedical subjects

P A Mitenko

Publications and source records attributed to P A Mitenko.

13 recordsLinked to original sources
PubMed1991

Long-term captopril in young and old patients with mild hypertension.

The decrease in renal blood flow (RBF) observed in patients with hypertension can be increased with converting enzyme inhibition (CEI). It is unknown whether the decrease in RBF observed with age can also be increased with CEI. This study compared the short- and long-term effects of captopril monotherapy in young (less than 50 years) and old (greater than 65 years) hypertensive patients. Captopril effectively decreased blood pressure in both groups (diastolic blood pressure less than 90 mm Hg), with the young patients requiring a lower dose (.7 mg/kg) than the elderly patients (1.2 mg/kg). Creatinine and para-aminohippurate clearances were maintained in both groups, with a decrease in renal vascular resistance being observed in the younger patients. Serum aldosterone levels fell significantly after each dose of captopril at all phases of the study, with no change observed in plasma renin levels. Atrial natriuretic peptide (ANP) level was increased in the elderly patients receiving placebo (48.8 +/- 8 pg/mL) when compared with the young subjects (24 +/- 3.8 pg/mL). Captopril did not alter ANP levels in either group.

Adult↗
PubMed1991

Prescribing patterns for older heavy drug users living in the community.

We report an analysis of prescription drugs claimed under a government-sponsored, universal Pharmacare program for community-dwelling adults aged greater than or equal to 50 years in Manitoba during 1975, 1978, 1981, and 1984. We limited our analysis to claimants who reported over six drugs in a year in order to control for effects of inflation and a changing deductible. The median number of prescribed drugs and the percent of claimants over age 50 years receiving prescriptions from multiple physicians decreased during the course of our study. In this sample of heavy drug users, age and sex did not consistently correlate with overall drug use, although there was correlation for specific drug groups. The relative ranking of prescribed drugs changed over the years, although benzodiazepines, thiazide diuretics, topical steroids, and codeine-containing analgesics remained near the top. Barbiturates and topical antibiotics showed the greatest drop in prescription rates; acetaminophen and beta-blockers increased the most. Using these community data, we project the prevalence of drug-related adverse events to be highest with beta-blockers, nonsteroidal antiinflammatory drugs, thiazide diuretics, and benzodiazepines.

Age Factors↗
PubMed1989

Nadolol antihypertensive effect and disposition in young and elderly adults with mild to moderate essential hypertension.

Nadolol was effective and well tolerated as once-daily monotherapy for mild to moderate essential supine diastolic hypertension (SDBP) in 10 young (mean age, 39 years) and 12 elderly (mean age, 68 years) patients in a single-blind, placebo-baseline, escalating-dose study. Doses required to reduce SDBP to 90 mm Hg were not different in young (1.08 +/- 0.21 mg/kg/day) and elderly (0.82 +/- 0.14 mg/kg/day) patients (mean +/- SE). Trough plasma nadolol concentrations at steady state were similar and were linearly related to dose in both groups. More unchanged nadolol was recovered in 24-hour urine samples from young subjects (15.6% +/- 1.9%) than from elderly ones (10.7% +/- 1.1%) (p = 0.028). With increasing nadolol doses, plasma norepinephrine concentration increased and isoproterenol sensitivity decreased in both young and elderly subjects, and creatinine clearance and plasma active renin levels were unchanged; plasma inactive renin levels increased in the young, and aldosterone concentration declined in the elderly with the lowest nadolol dose.

Adult↗
PubMed1988

Drug-associated hospital admissions in older medical patients.

A survey of drug-related admissions of patients aged 50 years and older was conducted at the Health Sciences Centre, Winnipeg to determine the interrelationship of risk factors, and isolate the effect of age. All nonelective medical admissions were prospectively assessed to determine the role of drug therapy as a contributory factor. Of the 863 eligible admissions, 162 exhibited at least one drug-related adverse patient event (DRAPE) at the time of hospitalization. This accounted for 19% of the admissions (23% of 718 admissions that involved prescription drugs). Although adverse drug reactions were responsible for many DRAPEs (48%), intentional noncompliance (27%), treatment failure (19%), alcohol (14%), and medication error (10%) were also frequent contributing causes. Drugs commonly implicated in DRAPEs were systemic steroids, digoxin, nonsteroidal anti-inflammatory agents, alpha-methyldopa, calcium channel blockers, beta-blockers, theophylline, furosemide, sympathomimetics, thiazides, and benzodiazepines. The risk of a DRAPE was related to the number of diseases prior to admission (r = 0.81; P less than .026) and the number of drugs used (r = 0.77; P less than .001). Age was not correlated with the risk of a DRAPE. Females had significantly more adverse drug reactions, although sex was not a predictor for overall DRAPE risk.

Aged↗
PubMed1987

Enprofylline disposition in the presence and absence of amoxycillin or erythromycin.

1 The kinetic disposition of a novel xanthine bronchodilator, enprofylline, was determined in young healthy male volunteers in the presence and absence of amoxycillin or erythromycin. These data were compared to those derived from a similar study of theophylline disposition in the presence and absence of erythromycin. 2 Erythromycin inhibited theophylline disposition only in those subjects in whom the control kinetic study was done after antibiotic ingestion, but the effect was modest. Erythromycin had no effect on enprofylline disposition. 3 Amoxycillin reduced the renal clearance of enprofylline, but the change was not statistically significant.

Adult↗
PubMed1986

Kinetic disposition of morphine in young males after intravenous loading and maintenance infusions.

Loading and maintenance infusions of morphine sulfate were administered to 5 young male patients 23-34-yr-old prior to elective surgery. Apparent steady-state plasma concentrations were achieved 30 minutes after the start of the drug infusion. The volume of distribution at steady-state (2.43 +/- 0.48 L X kg-1), beta elimination rate constant (0.700 +/- 0.162/h) and plasma clearance (1.66 +/- 0.33 L X kg-1 X h-1) were similar to values previously determined in young healthy subjects receiving a single bolus infusion. These data confirm our findings concerning morphine disposition in healthy young subjects and demonstrate the feasibility of achieving predictable plasma concentrations of morphine for future assessment of pharmacodynamic/pharmacokinetic relationships for this drug.

Adult↗
PubMed1986

Drug monitoring in the elderly.

Although the gut changes markedly with age no important differences in drug absorption have yet been demonstrated for any of a wide variety of drugs. Alterations in body structure and function can have important consequences on drug distribution in the elderly. There is a considerable reduction in total body mass with age and the proportion of lean body tissue decreases while there is a relative increase in the amount of adipose tissue. Protein binding of drugs can also be affected by age. Acidic drugs may be bound less in many older patients, mainly because of a general decrease in plasma albumin concentrations. Alpha-1-acid glycoprotein is of importance in the binding of basic drugs and its elevation in the elderly suggests that it may have an important effect on free drug concentration. Drug metabolism generally involves oxidative and conjugative reactions by the hepatic microsomal enzymes. There is little change in conjugative capacity with age although some oxidative pathways have been shown to be impaired. The steady decline in glomerular and tubular function with age is reflected in corresponding decreases in drug elimination for those drugs removed by this route.

Aged↗
PubMed1986

Salicylate metabolism: effects of age and sex in adults.

The plasma concentrations and urinary excretion rates of salicylic acid (SA) and some of its metabolites (salicyluric acid [SUA] and acyl and phenolic glucuronide conjugates) were measured after an oral dose of acetylsalicylic acid to 44 healthy subjects of both sexes 20 to 78 years old. There was no change in the SA absorption rate, and plasma clearance of SA was not affected by age or sex. The volume of distribution increased with age in men but not in women. Plasma concentrations of SUA rose with age as the renal clearance of this metabolite fell. The kinetic parameters Km and Vmax for the SA-to-SUA reaction did not change with age; Vmax was significantly higher in women than in men. Urinary recovery of SA and its metabolites essentially accounted for the administered dose, and was little influenced by age or sex. We conclude that these factors play a minor role in the disposition of salicylate.

Administration, Oral↗
PubMed1986

The pulmonary disposition of theophylline and its influence on human alveolar macrophage bactericidal function.

We studied the pulmonary disposition of theophylline by performing bronchoalveolar lavage on 19 normal, nonsmoking volunteers who had taken theophylline orally for 14 days. In addition, we determined the influence of theophylline on human alveolar macrophage bacterial phagocytosis, intracellular killing, and hydrogen peroxide release. We found a 1:1 relationship between serum and bronchoalveolar lavage theophylline concentrations when lavage fluid concentrations were corrected for saline dilution. We found marked impairment of the bactericidal activity of alveolar macrophages from theophylline-treated subjects (intracellular killing efficiency of 24.7 +/- 1.5% compared with 60.2 +/- 0.9% by macrophages from control subjects; p less than 0.001). This defect in alveolar macrophage bactericidal activity was inversely correlated with the bronchoalveolar lavage theophylline concentrations, and was corrected after the alveolar macrophages were cultured under serum-free conditions for 48 h. Theophylline significantly impaired alveolar macrophage release of hydrogen peroxide. Hence, theophylline may compromise lung host defenses by suppressing alveolar macrophage bactericidal activity and oxidative metabolite release.

Adult↗
PubMed1985

Effects of age and disease on the pharmacokinetics and pharmacodynamics of sulindac.

The disposition and effect on hemostasis of a single 150 mg dose of sulindac was studied in young healthy subjects and in older patients with arthritis. Older patients were restudied after 2 weeks of sulindac, 150 mg b.i.d. The only difference in disposition of the first dose was a reduced plasma sulfone metabolite concentration in the elderly patients with arthritis. Chronic sulindac dosing resulted in accumulation of the drug and its sulfone and sulfide metabolites in plasma to a greater extent than previously reported for young subjects. No differences in renal clearance of sulindac and its sulfone metabolite related to age or chronic drug dosing were observed. No renal excretion of the active sulfide metabolite was detected. Bleeding time in the elderly patients was shorter than in the young healthy subjects before sulindac dosing, but was prolonged in the elderly patients after 2 weeks of dosing to values similar to control data from the young healthy subjects. This change correlated weakly with plasma sulfide metabolite concentrations. Differences in bleeding time were not reflected in changes in platelet aggregation induced by adenosine diphosphate either with respect to age or chronic drug dosing. Our data provide no justification for lowering the recommended dose of sulindac for patients older than 65 years of age.

Adult↗
PubMedDate not supplied

Slow release theophylline disposition and effect in elderly patients with chronic obstructive lung disease: influence of dose formulation and institutionalization.

We studied the steady-state disposition of slow release theophylline tablets and granules in 12 institutionalized (I) and 12 community-dwelling (C) elderly patients with fixed chronic obstructive lung disease. Design was open label with random order crossover; each formulation was given 5 min before food every 12 h for 7 days. Age (median 70 y, range 55-88), sex, smoking status, and baseline lung function off drug were similar. Though plasma concentration (Cp) was higher with the tablets as was the area under the Cp vs time curve: 134 (74-252) vs 121 (75-197) mg h l-1; p = 0.028. The standard deviation of Cp over one dose interval was lower with the granules. FEV 1.0 was slightly improved over baseline. Dose required to reach target Cp was higher in the institutionalized group (12.6 vs 8.6 mg kg-1 day-1; p = 0.003) as was apparent clearance; I:94 (43-148) ml hr-1 kg-1 vs C:68 (34-163); p = 0.003. Although bioavailability was slightly reduced for the granules, fluctuations of Cp was less, and we failed to find a food effect that was clinically important in geriatric subjects.

Aged↗