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Biomedical subjects

C W Loomis

Publications and source records attributed to C W Loomis.

40 records · Page 3Linked to original sources
PubMed1980

Drug interactions of amitriptyline and nortriptyline with warfarin in the rat.

Treatment of rats with amitriptyline or nortriptyline for 6 days at 6, 15 and 30 mg/kg produced no increases in the activities of aniline hydroxylase and aminopyrine N-demethylase or the content of microsomal protein and cytochrome P-450. Significant decreases in aminopyrine N-demethylase activity and cytochrome P-450 content were observed at 30 mg/kg. This inhibition of activity appeared to be at the level of cytochrome P-450 and not a cytotoxic effect in liver cells. Concomitant administration of amitriptyline or nortriptyline (6, 15 and 30 mg/kg)with warfarin to rats produced a dose dependent increase in the prothrombin time. At high doses of the tricyclic antidepressants, these increases in prothrombin time correlated with increases observed in the plasma half-life of warfarin. In vitro studies suggested that amitriptyline and nortriptyline inhibited the metabolism of warfarin. A double-reciprocal plot (Lineweaver-Burk method) showed this inhibition to be competitive. Nortriptyline produced greater inhibition of warfarin metabolism than amitriptyline and correspondingly greater enhancement of the anticoagulant effect.

Amitriptyline↗
PubMed1979

The calcium carbimide-ethanol interaction: effects of ethanol dose.

In a double-blind, placebo-controlled study involving five male alcoholic volunteers, oral administration of 0.7 mg/kg of calcium carbimide (CC) 12 hr before ingestion of ethanol (0.125, 0.25, and 0.5 gm/kg) produced an interaction consisting of increased blood acetaldehyde level, tachycardia, and decreased diastolic blood pressure. The order of intensity of the interaction with regard to ethanol dose was 0.5 greater than 0.25 greater than 0.125 k gm/kg. The subjects were aware of a CC-ethanol interaction only for 0.25 and 0.5 gm/kg of ethanol, for which heart rate was elevated above 100 bpm. With the criterion of heart rate above 100 as indicative of the CC-ethanol interaction, the onset was 0.25 and 0.38 hr for the 0.5 and 0.25 gm/kg ethanol doses and the duration of the interaction was 1.0 and 0.38 hr, respectively. There were positive linear correlations between blood acetaldehyde level and both heart rate and pulse pressure. There was appreciable individual variability in the intensity and duration of the interaction. Pretreatment with CC reduced the rate of ethanol metabolism at the 0.5 gm/kg ethanol dose.

Acetaldehyde↗
PubMed1978

A study of the calcium carbimide-ethanol interaction in man.

In six male alcoholic volunteers, oral administration of calcium carbimide (0.7 mg/kg) before ingestion of ethanol (0.5 g/kg) produced an interaction consisting of increased blood acetaldehyde level, tachycardia and increased pulse pressure, which was due mainly to decreased diastolic blood pressure. For these experimental conditions, calcium carbimide had a duration of action of at least 24 h to produce an interaction with ethanol. The order of intensity of the interaction with regard to the calcium carbimide pretreatment time interval was 4 greater than 8 approximately 12 greater than 24 h. Using the criterion of heart rate above 100 as indicative of the calcium carbimide-ethanol interaction, the onset was 0.13, 0.25, 0.25 and 0.38 h for the 4-, 8-, 12- and 24-h pretreatment experiments and the duration of the interaction was 1.6, 1.0, 1.0 and 0.12 h, respectively. There were positive linear correlations between acetaldehyde level and heart rate and between acetaldehyde level and pulse pressure. There was appreciable interindividual variability in the heart rate and blood pressure responses. Increased blood acetaldehyde level seemed to be required for the physiological changes to occur. Calcium carbimide pretreatment at the 4-h interval produced increased blood ethanol level for the last hour of the interaction and reduced the rate of ethanol metabolism.

Acetaldehyde↗