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Biomedical subjects

J Feely

Publications and source records attributed to J Feely.

At least 37 records · Page 2Linked to original sources
PubMed1990

Severity of cirrhosis and the relationship of alpha 1-acid glycoprotein concentration to plasma protein binding of lidocaine.

The concentration of alpha 1-acid glycoprotein, the major determinant of the plasma protein binding of basic drugs, and the extent of lidocaine protein binding was related to the severity of liver disease in 30 cirrhotic patients. In comparison with matched control subjects, alpha 1-acid glycoprotein concentration (77 +/- 7 versus 37 +/- 3 mg/dl; mean +/- SEM; p less than 0.01) and lidocaine binding (69% +/- 2% versus 35% +/- 2%; p less than 0.01) was markedly reduced. There was a significant negative correlation (r = 0.78; p less than 0.01) between free lidocaine and alpha 1-acid glycoprotein concentration. Furthermore, both were significantly related to the severity of liver disease, as assessed by use of the Child Turcotte classification.

Adult↗
PubMed1990

Tissue zinc status and drug elimination in patients with chronic liver disease.

1. The zinc status and drug-metabolizing ability of 15 patients with histologically diagnosed hepatic cirrhosis were studied. Zinc status was assessed using both serum and leucocyte zinc concentrations, and drug-metabolizing ability was assessed by antipyrine kinetics. 2. Patients with cirrhosis were found to have lower serum and leucocyte zinc concentrations when compared with a healthy control group. 3. Leucocyte zinc content and antipyrine clearance were correlated. Those patients with the lowest leucocyte zinc content had the greatest impairment of drug metabolism. Antipyrine elimination and serum zinc concentrations were not correlated. 4. Leucocyte zinc concentrations and antipyrine clearance were not influenced by the severity of liver dysfunction, as assessed by using the Child Turcotte classification. 5. These results suggest that tissue zinc depletion in some patients with hepatic cirrhosis may explain in part the impaired capacity to metabolize drugs.

Antipyrine↗
PubMed1990

Allopurinol influences aminophenazone elimination.

The authors observed an interaction between allopurinol and both theophylline and warfarin in 2 patients. To determine the possible effect of allopurinol on hepatic oxidative metabolism a [14C]-aminophenazone (aminopyrine) breath test was performed before and during treatment with allopurinol 100mg daily in 5 patients with hyperuricaemia. Allopurinol prolonged the [14CO2]-aminophenazone half-life from 72 +/- 13 to 104 +/- 16 minutes (mean +/- SEM, p less than 0.05). It is possible that allopurinol may produce clinically significant drug interactions through an inhibitory effect not only on xanthine oxidase metabolism but also on oxidative metabolism.

Allopurinol↗
PubMed1990

Effects of drugs on glucose tolerance in non-insulin-dependent diabetics (Part I).

Non-insulin-dependent diabetes mellitus (NIDDM) is being increasingly diagnosed as its importance as a risk factor for the development of cardiovascular disease continues to be recognised. Good metabolic control remains a major goal of drug therapy as it decreases the severity and incidence of diabetic complications. Many drugs have been known to interfere with glucose control, either in a beneficial or, more commonly, in a deleterious fashion. Unfortunately in many instances drug-induced effects have not been looked at specifically in NIDDM. Thiazide diuretics have been shown to cause a deterioration in glucose control not only in the general population but especially in patients who have impaired glucose tolerance. While the effect appears less with potassium supplementation and the lower dosage employed nowadays, thiazide diuretics are best avoided in diabetic patients. Loop diuretics have been reported to reduce glucose control to a lesser extent than thiazides. Although indapamide would appear not to interfere with blood sugar control in NIDDM, higher doses that cause potassium loss may cause a deterioration. beta-Adrenoceptor antagonists have been reported to cause a rise in blood sugar and glycosylated haemoglobin in NIDDM. The effect may be more marked in patients on oral hypoglycaemic agents as opposed to diet alone and in those on concomitant thiazide diuretics. The greatest effect was seen with propranolol, and the least with cardioselective and the less lipophilic beta-blockers. It is of interest that alpha-blockade with prazosin seems to antagonise beta-adrenoceptor blocker-induced deterioration in glucose control. The calcium antagonists have differing effects which may be structure related. In some, but not all, studies use of the dihydropyridines such as nifedipine has been associated with a deterioration in glucose control in NIDDM. Long term studies are needed to assess definitively their effect on glucose control. Verapamil, on the other hand, has in 1 small study been found to have a beneficial effect on glucose control in NIDDM. Centrally acting alpha-agonists such as the antihypertensive drug clonidine have not been shown to result in a deterioration in glucose control when used in NIDDM, although there are isolated case reports. Long term therapy with the more specific agonist guanfacine was reported in 1 uncontrolled study to have a beneficial effect on glucose tolerance in NIDDM. Uncontrolled studies suggest that phenothiazines may aggravate diabetic control. The significance of a number of recent observations is not fully clear.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Flash visual evoked responses in the early encephalopathy of chronic liver disease.

In recent years many variants of EEG sensory evoked responses have been studied as potential diagnostic aids in the detection and quantification of hepatic encephalopathy (HE). This study assesses the value of the flash visual evoked response (VER). Twenty-six controls and 21 non-encephalopathic and 12 encephalopathic (grade 1/2), biopsy-proven, cirrhotic patients were assessed clinically, psychometrically, and electrophysiologically. Flash VER from three different leads were obtained from each patient. Data from the fronto-occipital leads gave the best differentiation between the subjects. The P2 and N3 peak latencies were significantly increased in the two liver groups and correlated with the mental state and psychometric results. The N3 latency had a 92% specificity and a 50% sensitivity in the detection of grade 1/2 HE. This study suggests that the N3 latency changes may be a good marker of early clinical HE and useful in the longitudinal assessment of individual patients.

Adult↗
PubMed1990

Altered pharmacodynamics in the elderly.

The importance of age-related changes in drug sensitivity is increasingly appreciated. More conclusive evidence is now being presented in combined kinetic and dynamic studies. The type, intensity, and duration of drug action may be affected, ranging from therapeutic failure to major drug toxicity. Alterations in physiologic and homeostatic systems, including the autonomic system, baroreceptors, thermoregulation, and balance, have been described. These may explain the propensity to postural hypotension, falls, hypothermia, and confusion, particularly following drug-induced decrements in these systems. Studies on the sensitivity to individual drugs produce a varied picture emphasizing the danger of generalizations. An increased sensitivity to many agents affecting the central nervous system, including benzodiazepines, halothane, metoclopramide, and narcotic analgesics, is becoming apparent. For the latter this may also be accompanied by an age-associated qualitative difference in toxicity. Whereas there is conclusive evidence of a reduced responsiveness to propranolol, the data are conflicting for calcium antagonists. The increased hypotensive response to ACE inhibitors is more likely due to kinetic factors. The anticoagulant response to warfarin is enhanced. Evidence is also emerging of a wide divergence in the sensitivity of different systems to the same drug--with aging the inotropic effect of theophylline is increased, but the bronchodilator response is decreased. It is becoming clear also that there is a need to separately study certain subgroups of the elderly population.

Aged↗
PubMed1989

Do subjects with stiff arteries have high blood pressure?

It has been argued that age-related increases in arterial stiffness could lead to spuriously high indirect blood pressure measurements, with consequent overdiagnosis of hypertension in older patients. To study the relationship between arterial stiffness and blood pressure, we identified patients with 'arterial stiffness', using Osler's manoeuvre, and compared their blood pressure levels with patients of a similar age. A total of 250 hospital inpatients were assessed independently by two doctors. In the 198 patients (79%) where both observers agreed on Osler's manoeuvre status, positive Osler's manoeuvre was uncommon under the age of 50 years but became more common thereafter, rising to 58% of patients aged over 75 years. However, blood pressure levels were similar in each age group, irrespective of Osler's manoeuvre status. We conclude that increased arterial stiffness as measured by Osler's manoeuvre is not necessarily associated with raised blood pressure levels in the elderly.

Adolescent↗
PubMed1987

Calcium channel blocker drugs and diabetic control.

Calcium channel blockers are now widely used and there have been case reports of hyperglycemia with nifedipine. In a double-blind, randomized, crossover study of the effects of 4 weeks of therapy, each with two dihydropyridine calcium channel blocker drugs, nifedipine and nicardipine, glucose tolerance, plasma insulin levels, and hemoglobin A1 were assessed in 20 patients with non-insulin-dependent diabetes (mean age 59 years). There was no significant difference in glucose tolerance on active therapy (AUC: control, 548.3 +/- 24.8; nifedipine, 559.3 +/- 41.0; and nicardipine, 589.3 +/- 40.3). Similarly, despite producing significant hemodynamic effects, these drugs produced no significant effect on plasma insulin and hemoglobin A1 levels. Calcium channel blocker drugs may be useful alternatives to thiazide diuretics and beta-blockers in the treatment of ischemic heart disease and hypertension, especially in patients with diabetes.

Adult↗