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Biomedical subjects

J Feely

Publications and source records attributed to J Feely.

At least 145 records · Page 8Linked to original sources
PubMed1983

Effect on apparent liver blood flow of histamine-receptor blockers and inhibition of prostaglandin synthesis.

We have recently shown that histamine H2-receptor blockade with cimetidine reduces apparent liver blood flow. To determine the effects of inhibition of prostaglandin synthesis and of H1-receptor blockade and of their additive effects when combined with cimetidine (600 mg), we estimated liver blood flow from the clearance of a single dose (0.5 mg/kg) of indocyanine green (ICG) in six healthy subjects after indomethacin (50 mg. three times during 24 hr) and chlorpheniramine (8 mg. three times during 24 hr). Indomethacin and chlorpheniramine reduced ICG estimated liver blood flow by 18 +/- 3% and 13 +/- 4% (mean +/- SEM). When cimetidine was added to indomethacin or chlorpheniramine, the reductions in flow of 22 +/- 6% and 19 +/- 5% were not significantly greater than that after indomethacin, chlorpheniramine, or cimetidine alone (16 +/- 6%). These data suggest that both histamine acting through H1- and H2-receptors and prostaglandins may influence liver blood flow in man and are consistent with evidence from animal experiments that suggest a role for prostaglandins in H2-mediated vascular responses.

Adult↗
PubMed1983

Effect of thyrotoxicosis on liver blood flow and propranolol disposition after long-term dosing.

The effects of thyrotoxicosis on Liver blood flow and propranolol disposition were followed in five patients while thyrotoxic and when euthyroid. Propranolol was taken orally to achieve steady state and then radiolabeled drug was given simultaneously by intravenous injection. Thyrotoxicosis was associated with doubling of both oral and systemic clearances of unbound propranolol, which resulted in an approximately 50% reduction in blood concentrations after oral doses. These changes were attributable to increases in hepatic blood flow and drug-metabolizing activity of the liver. The propranolol elimination t 1/2 was not affected by thyrotoxicosis since the enhanced clearance was offset by a change in volume of distribution. These findings may explain the reduction of plasma propranolol concentration and many of the therapeutic failures reported in the treatment of thyrotoxicosis. The dose required to achieve therapeutic blood concentrations of propranolol in thyrotoxic patients is variable and will usually be substantially larger than that required for euthyroid patients.

Administration, Oral↗
PubMed1983

Interaction of cimetidine with other drugs.

After five years' extensive use of cimetidine, drug interactions have emerged as one of its major adverse effects. Clinically important interactions with warfarin, phenytoin, diazepam, chlormethiazole, propranolol, lidocaine, and a number of other drugs have been reported. An appreciation of the variety of underlying mechanisms, inhibition of drug metabolism, decreased liver blood flow, and altered drug distribution should reduce the risk of further drug interactions with cimetidine.

Aged↗
PubMed1983

Effect of inhibitors of prostaglandin synthesis on hepatic drug clearance.

The effect of inhibition of prostaglandin synthesis on the systemic clearance of indocyanine green and antipyrine was studied in seven subjects. Antipyrine clearance was not altered by indomethacin suggesting that oxidative metabolism was not affected. Both aspirin and indomethacin decreased the clearance of indocyanine green presumably by reducing liver blood flow. These results suggest that an effect of inhibitors of prostaglandin synthesis on hepatic drug clearance is likely to be confined to high clearance drugs when given systemically.

Adult↗
PubMed1983

Lack of effect of ranitidine on the disposition of lignocaine.

Cimetidine has been shown to alter the disposition of lignocaine and other drugs that are highly extracted by the liver. In a placebo controlled study ranitidine (150 mg twice daily) did not alter the elimination half-life, systemic clearance or distribution of lignocaine (mg/kg) in six healthy subjects. The interaction with cimetidine appears to be unrelated to histamine H2-receptor antagonism.

Adult↗
PubMed1983

Effects of feeding on the systemic clearance of indocyanine green and propranolol blood concentrations and plasma binding.

In six healthy subjects a 250 g steak significantly increased the systemic clearance of indocyanine green. During a steady-state infusion of propranolol there was a rapid decrease (mean 35%) in blood propranolol concentrations within 5 min of feeding and levels were reduced for 30 min before gradually returning towards the pre-feeding. These results suggest that the systemic clearance of high extraction drugs may be increased immediately following food.

Adult↗
PubMed1983

Enzyme induction with rifampicin; lipoproteins and drug binding to alpha 1-acid glycoprotein.

Hepatic enzyme induction has been reported to increase lignocaine binding, alpha 1-acid glycoprotein concentration and high density lipoprotein (HDL) cholesterol. In eight volunteers treated with rifampicin for 3 weeks there was no significant alteration in these three variables although their antipyrine clearance was significantly increased. In 10 patients with pulmonary tuberculosis treated with rifampicin (mean 5 months) the degree of serum protein binding of lignocaine, alpha 1-acid glycoprotein and HDL-cholesterol concentration was not different from that of matched control patients. These results suggest that differential induction of these variables may occur.

Adult↗
PubMed1983

Antithyroid effect of chlorpropamide?

1 The relationship between plasma chlorpropamide concentration and thyroid function was examined in 87 maturity onset diabetic patients receiving chronic therapy. 2 Although plasma chlorpropamide concentration was weakly negatively correlated with serum thyroxine (r = 0.33, P less than 0.01) the mean serum thyroxine and thyrotrophin (TSH) were not different from that of a matched control group of diabetics treated with diet alone. 3 Serum thyroxine was negatively correlated with the duration of diabetes in both groups. 4 These results suggest that chlorpropamide does not have a clinically significant antithyroid effect.

Adult↗
PubMed1982

Effects of cimetidine on the elimination and actions of ethanol.

The influence of cimetidine hydrochloride (300 mg four times daily for seven days) on plasma ethanol concentrations and the subjective assessment of intoxication after a single oral dose of ethanol (0.8 g/kg) were investigated in a randomized double-blind placebo controlled study in six volunteers. Compared with the placebo, cimetidine produced a small increase in both the peak plasma ethanol level (from 146 +/- 5.2 to 163 +/- 7.6 mg/dL, mean +/- SEM) and th area under the ethanol concentration time curve (from 717 +/- 17 to 771 +/- 44 mg/dLXhr). In addition, using a visual analogue scale, subjects rated themselves more intoxicated at their peak of intoxication while receiving cimetidine. These results suggest that cimetidine has a small effect on the handling of ethanol in humans.

Adult↗
PubMed1982

Increased drug effect induced by surgery.

1 A thyrotoxic patient receiving a constant dose of propranolol and digoxin developed marked bradycardia postoperatively. 2 Compared to preoperative levels there was a considerable rise post-operatively in both plasma propranolol and serum digoxin steady-state concentrations. 3 Surgery by effecting drug disposition and disease processes may significantly alter drug handling in the perioperative period.

Bradycardia↗
PubMed1982

Increased toxicity and reduced clearance of lidocaine by cimetidine.

Cimetidine reduced liver blood flow and the systemic clearance of drugs, such as propranolol, that are highly extracted by the liver. In a randomized placebo-controlled study, we examined the influence of cimetidine, 300 mg four times daily for 1 d, on the disposition of lidocaine, 1 mg/kg body weight by a 10-minute intravenous infusion. Cimetidine reduced the systemic clearance of lidocaine from 766 +/- 50 mL/min to 576 +/- 47 mL/min (p less than 0.05); the apparent volume of distribution at steady-state and the degree of plasma protein binding of lidocaine also were decreased. Five of the six subjects noted lidocaine toxicity during the cimetidine infusion in contrast to one subject on the placebo day. The peak lidocaine concentration (mean +/- SE) was 50% +/- 10% higher when subjects received cimetidine. This study provides additional evidence that the effect of cimetidine on the elimination of other drugs has multiple factors, and shows a previously unrecognized mechanism, involving altered initial drug distribution, whereby the interaction of cimetidine with other drugs may cause toxicity.

Adult↗
PubMed1981

Reduction of liver blood flow and propranolol metabolism by cimetidine.

We studied the influence of cimetidine on liver blood flow in eight normal subjects. Cimetidine acutely reduced liver blood flow during fasting by almost 25 per cent, as measured by indocyanine green clearance. Chronic cimetidine therapy (300 mg four times daily for seven days) reduced the flow by 33 per cent, as measured over eight hours by calculating the relative disposition of oral and intravenous propranolol. In addition to reducing the clearance of intravenous propranolol by decreasing live blood flow, cimetidine also inhibited the metabolism of oral propranolol and thereby further reduced elimination. The reduction in clearance of oral propranolol correlated positively (r = 0.87, P less than 0.05) with the average steady-state concentration of plasma cimetidine, suggesting that the inhibition of drug metabolism by cimetidine is dose related. Pulse rates at rest were markedly lower after propranolol plus cimetidine than after propranolol alone. The reduction in liver blood flow produced by cimetidine has important therapeutic implications for patients with alterations in liver and gastrointestinal blood flow and when drugs are used whose hepatic elimination depends on liver blood flow.

Administration, Oral↗