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Biomedical subjects

J Feely

Publications and source records attributed to J Feely.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1987

The effect of calcium channel blockade with nifedipine on splanchnic and systemic haemodynamics in cirrhosis.

The splanchnic and systemic haemodynamic effects of a single sublingual dose of nifedipine (slow calcium channel blocker) in nine patients with cirrhosis of the liver and portal hypertension were studied. Nifedipine produced a significant reduction in the mean arterial blood pressure (98 +/- 5.3 vs. 86 +/- 5 mmHg, P less than 0.05) but did not alter the mean heart rate, portal venous pressure or total liver blood flow. The systemic antihypertensive effect of nifedipine can be achieved without altering liver blood-flow in patients with chronic liver disease and portal hypertension.

Hemodynamics↗
PubMed1987

The effects of ageing on aminopyrine and caffeine breath tests in the rat.

The influence of ageing on demethylation of 14C-aminopyrine (AP) and 14C-caffeine (Caf) in Wistar littermate rats was studied serially using the 14CO2-breath test. In both sexes, the elimination half-life (t1/2) of 14C-AP fell from a mean of approximately 75 min when weaned at 17 days to 45 min at maturity (49 days); thereafter t1/2 became prolonged, being most prolonged (82 min) in elderly male rats (210 days). Similarly, t1/2 of 14C-Caf was also prolonged with ageing. These studies using in vivo and longitudinal techniques indicate the importance of ageing on hepatic demethylation.

Aging↗
PubMed1987

Effects of chronic treatment with amiodarone on hepatic demethylation and cytochrome P450.

The effect of chronic treatment with amiodarone on hepatic oxidative metabolism using an in-vivo [14C]aminopyrine breath test and on hepatic cytochrome P450 was examined in Wistar rats. Aminopyrine demethylation was significantly impaired but returned to pretreatment values following amiodarone for 4 weeks. In contrast the levels of cytochrome P450 were significantly depressed during treatment and at 4 weeks following treatment. While an inhibitory effect on oxidative metabolism may explain the reported drug interactions with amiodarone, the discrepancy between its in-vivo effects and cytochrome P450 levels may suggest the development of 'compensatory' extra-hepatic site of drug metabolism.

Aging↗
PubMed1987

Clinical pharmacokinetics and endocrine disorders. Therapeutic implications.

Endocrine disorders are common and produce widespread changes in cellular and organ function. Alterations in the sensitivity of patients with thyroid disorders to digoxin, anticoagulants and sedatives have been recognised for many years. Many of the recently documented kinetic alterations in endocrine patients are explicable on the basis of disease-induced changes in hepatic drug metabolism, protein binding and renal function. In hyperthyroidism the rate of absorption of paracetamol, propranolol and oxazepam is increased due to increased gastrointestinal motility. The volume of distribution of propranolol and digoxin is increased and there is decreased binding of both basic and acidic drugs as a consequence of alterations in alpha 1-acid glycoprotein and albumin concentration. The rate of glucuronidation of paracetamol and oxazepam is increased in hyperthyroidism. While oxidative metabolism of antipyrine, propranolol, metoprolol and theophylline is enhanced, the clearance of a number of other agents, including diazepam, warfarin, antithyroid drugs and phenytoin, is unaltered. The systemic clearance of propranolol is enhanced as a consequence of a 50% increase in liver blood flow. The rate of elimination of a number of endogenous substances, including cortisol, thyroid hormones and insulin, also appear to be enhanced. Hyperthyroidism has a variable effect on renal function, with a possible increase in digoxin elimination, but no effect on the clearance of renally excreted beta-blockers, atenolol, sotalol and nadolol. These kinetic changes suggest that individualization and higher than normal dosage of propranolol is necessary to control hyperthyroidism, and in thyrotoxic atrial fibrillation higher doses of digoxin or additional therapy with beta-blockers, or verapamil, may be indicated. The increased sensitivity of thyrotoxic patients to warfarin suggest care with dosage and frequent monitoring of response are warranted. Less information is available concerning hypothyroidism, but there is a general trend for decreased absorption of paracetamol and propranolol. In addition, the volume of distribution of digoxin is reduced, as is renal clearance. Limited studies suggest no alteration in the glucuronidation of oxazepam, but antipyrine clearance appears to be reduced. Steady-state propranolol concentrations are elevated in hypothyroidism and there appears to be a decreased metabolism of thyroid hormones and cortisol. Preliminary information suggests the binding of propranolol is increased. Thus, in the treatment of hypothyroid patients, a lower dosage of propranolol may be required.(ABSTRACT TRUNCATED AT 400 WORDS)

Endocrine System Diseases↗
PubMed1986

Profound reduction in morphine clearance and liver blood flow in shock.

In six patients with septic shock apparent liver blood flow was significantly reduced compared with two patients restudied on recovery from shock and a group of four matched unshocked patients undergoing intensive care (287 +/- 23 ml/min vs 870 +/- 164 ml/min; mean +/- SEM). In the shocked patients the elimination half-life of morphine was significantly prolonged (13.2 +/- 3.5 h vs 5.9 +/- 1.4 h; mean +/- SEM) and the systemic clearance of morphine reduced by 53%, in comparison with the non-shocked patients. In both groups, morphine elimination was markedly delayed compared with previously reported observations in normal subjects and surgical patients. Care should be exercised with the use of drugs with a high hepatic extraction ratio in shocked patients.

Aged↗
PubMed1986

Reduction of liver plasma flow by caffeine and theophylline.

Caffeine and theophylline block the vasodilating effects of adenosine and may act to enhance sympathoadrenal discharge and activate the renin-angiotensin system. To determine if these methylxanthines might thereby have effects on regional blood flow, we studied the influence of caffeine and theophylline on apparent liver plasma flow (LPF) in normal subjects as assessed by indocyanine green clearance. Oral caffeine, 250 mg, reduced LPF by 19% from 630 +/- 150 to 510 +/- 120 ml/min (P less than 0.001). Intravenous theophylline (4.3 mg/kg) reduced LPF by 15% from 550 +/- 50 to 470 +/- 90 ml/min (P less than 0.05). These methylxanthine-induced falls in LPF may alter the disposition of concomitantly administered drugs. Because of their widespread use in Western society, caffeine and theophylline may be major determinants of liver blood flow in the general population. They may therefore prolong the t1/2 and increase steady-state levels of hepatically eliminated drugs.

Adenosine↗
PubMed1985

The clinical and metabolic responses to early surgical treatment for hyperthyroid Graves' disease: a comparison of three pre-operative treatment regimens.

We have compared the clinical and metabolic responses of three groups of patients undergoing subtotal thyroidectomy for hyperthyroid Graves' disease. These patients were prepared for surgery with propranolol alone, propranolol plus potassium iodide or the long acting beta-adrenoceptor antagonist nadolol plus potassium iodide. Pre-treatment with potassium iodide reduced serum T4 to normal or subnormal in all patients. Patients in the propranolol group had significantly higher pulse rates and temperatures after operation and one patient developed an exacerbation of the hypermetabolic state. The perioperative rise in serum cortisol and blood glucose was delayed in patients in the propranolol group and this was also noted in one severely hyperthyroid patient on propranolol + potassium iodide. Nadolol was administered once daily as compared to multiple daily doses with propranolol. Despite this, plasma nadolol levels were consistently higher throughout the perioperative period while propranolol levels in patients on both propranolol alone and propranolol + potassium iodide were highly variable and sometimes undetectable. We conclude that, in the rapid preparation of patients with hyperthyroid Graves' disease for surgery, the combination of nadolol + potassium iodide has significant advantages over the other two regimens.

Adult↗
PubMed1984

Beta-adrenoceptor blockade and anaesthesia for thyroidectomy.

The administration of beta-adrenoceptor blocking drugs in the pre-operative preparation and operative management of thyrotoxic patients undergoing subtotal thyroidectomy is reviewed. Particular reference is made to some of the recent advances and it is emphasised that there has been a considerable reduction in the incidence of problems following judicious use of these drugs. The choice of anaesthetic technique employed for thyroidectomy is less important than the degree of control of thyrotoxicosis by the beta-adrenoceptor blocking drug. Propranolol has proved safe and effective for the majority of patients. The longer acting agent nadolol is easier to administer, particularly in the peri-operative period. Patients are rendered less thyrotoxic and safety thereby enhanced by adding potassium iodide for 10 days preoperatively. The combination of nadolol and potassium iodide offers real advantages in the preparation of the thyrotoxic patient for surgery.

Adrenergic beta-Antagonists↗
PubMed1984

Factors affecting the response to inhibition of drug metabolism by cimetidine--dose response and sensitivity of elderly and induced subjects.

The effect of cimetidine on oxidative drug metabolism was characterised using antipyrine clearance in a group of healthy volunteers. In six subjects cimetidine produced a dose dependent reduction of antipyrine clearance: 400 mg/day (16.8 +/- 2.2%, mean +/- s.e. mean), 800 mg/day (26.3 +/- 1.5%) and 1600 mg/day (33.5 +/- 2.4%). The effect of cimetidine (800 mg/day) was of similar magnitude (approximately 25%) in two groups of six young (21-26 years) and six elderly (65-78 years) subjects. The effect of pretreatment begun just 1 h before administration of antipyrine was similar to that of 24 h pretreatment and that reported for chronic cimetidine pretreatment. The percentage reduction in antipyrine clearance produced by cimetidine 800 mg/day was greater (44 +/- 5 vs 24 +/- 3%; P less than 0.05) in six subjects who had been pretreated with the hepatic enzyme inducer rifampicin (600 mg/day for 21 days) than in the control uninduced state. Although cimetidine was capable of rapidly reversing the effect of rifampicin on antipyrine clearance, following withdrawal of both rifampicin and cimetidine there was still evidence of enzyme induction. These results suggest that the effect of cimetidine on oxidative metabolism is dose dependent, is more marked in enzyme induced subjects, is independent of the duration of pretreatment and is of similar magnitude in young and elderly subjects.

Adult↗
PubMed1984

Nifedipine increases and glyceryl trinitrate decreases apparent liver blood flow in normal subjects.

The effects of sublingual nifedipine (10 mg) and of glyceryl trinitrate (500 micrograms), which produce arterial and venous vasodilatation respectively, on indocyanine green estimated apparent liver blood flow (LBF) were studied in six healthy volunteers. Nifedipine significantly increased (33 +/- 12%; mean +/- s.e. mean) and glyceryl trinitrate significantly reduced (18 +/- 3%) LBF. There was a positive relationship (r = 0.92, P less than 0.05) between the reduction in mean arterial pressure produced by nifedipine and the percentage increase in LBF. These results show that single doses of nifedipine and glyceryl trinitrate significantly alter LBF.

Adult↗
PubMed1984

Use of beta-adrenoceptor blocking drugs in hyperthyroidism.

There is an increasing use and variety of beta-adrenoceptor blocking agents (beta-blockers) available for the treatment of hyperthyroidism. Recent comparative studies suggest that atenolol (200mg daily), metoprolol (200mg daily); acebutolol (400mg daily), oxprenolol ( 160mg daily), nadolol ( 80mg daily) and timolol (20mg daily) produce a beneficial clinical response equal to that seen with propranolol ( 160mg daily). Most beta-blockers reduce resting heart rate by approximately 25 to 30 beats/min, although a lesser reduction is seen with those possessing intrinsic sympathomimetic activity such as oxprenolol and pindolol. While earlier studies employing large doses of intravenous propranolol concluded that beta-blockade reduced myocardial contractility, more recent non-invasive studies suggest that the predominant cardiac effect is on heart rate. In patients with cardiac failure, beta-blockers may, however, produce a profound fall in cardiac output. Nevertheless, in combination with digoxin they may be useful in controlling the atrial fibrillation of thyrocardiac disease. beta-Blockers improve nervousness and tremor (although to a lesser extent with cardioselective agents) and severe myopathy, and they also reduce the frequency of paralysis in patients with thyrotoxic periodic paralysis. There is often subjective improvement in sweating but usually no major effect on eye signs. Recent studies show a 10% reduction in oxygen consumption/basal metabolic rate with long term oral use of selective or nonselective beta-blockers. In addition, many agents (propranolol, metoprolol, nadolol and sotalol but not acebutolol, atenolol or oxprenolol) reduce circulating tri-iodothyronine (T3) concentration by between 10 and 40%, although the clinical significance of this effect (if any) is not established. beta-Blockers may also have endocrinological effects on gastrin, cyclic AMP, catecholamines and other hormone levels. Given in adequate dosage, propranolol has been shown to control thyrotoxic hypercalcaemia. Minor side effects (nausea, headaches, tiredness, etc.) are quite common but overall beta-blockers are well tolerated by the thyrotoxic patient. The major use of these drugs is in symptomatic control while awaiting definitive diagnosis or treatment. As an adjunct to antithyroid drugs or radioactive iodine, beta-blockers will produce a satisfactory clinical response in the weeks to months before these forms of therapy produce a euthyroid state. beta-Blockers are more convenient than antithyroid drugs in the control of patients receiving therapeutic radioiodine, in that continuous therapy and assessment of biochemical response is possible.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic beta-Antagonists↗