Interaction of Alcohol With Therapeutic Drugs and Drugs of Abuse

Sands, Brian F.; Knapp, Clifford M.; Ciraulo, Domenic A.

doi:10.1007/978-3-642-78435-4_19

Cited by 3 publications

(2 citation statements)

References 174 publications

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“…34 The significant increase in cocaine volume of distribution due to alcohol coadministration is caused by increased cocaine tissue distribution, which may have resulted from altering the binding of cocaine in plasma and tissues. 35 These results are not contradictory to the decreased brain-toplasma AUC ratio when cocaine was administered with alcohol. Because the microdialysis technique used for the determination of cocaine brain ECF concentration measures only the free (unbound) cocaine concentration in the brain ECF.…”

Section: Discussionmentioning

confidence: 89%

“…Cocaethylene, a pharmacologically active metabolite formed only when both cocaine and alcohol are administered, has been shown to possess cocaine-like effects and can increase dopamine concentration after administration in experimental animals. [34][35][36][37][38] Another contributing factor may be related to alcohol administration because alcohol has been shown to increase dopamine brain concentrations after acute or chronic administrations in experimental animals. 39 It is also possible that the increased tissue distribution of cocaine due to alcohol pretreatment may result in higher (bound + free) brain tissue concentration of cocaine, which can lead to higher dopamine concentrations.…”

Section: Discussionmentioning

confidence: 99%

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Cocaine and alcohol interactions in the rat: Effect on cocaine pharmacokinetics and pharmacodynamics

Pan

Hedaya

1999

Journal of Pharmaceutical Sciences

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The effect of alcohol coadministration on cocaine pharmacokinetics and pharmacodynamics was investigated in awake, freely moving rats. Cocaine plasma and brain extracellular fluid (ECF) concentration-time profiles were characterized after intraperitoneal (ip) administration of 30 mg/kg cocaine to rats that were pretreated with either normal saline or alcohol at 5 g/kg in a balanced crossover experimental design. The neurochemical response to cocaine administration, measured as the change in dopamine concentration in the nucleus accumbens (N ACC) and the change in the mean arterial blood pressure were monitored simultaneously. Intragastric alcohol administration significantly increased cocaine systemic bioavailability after ip administration from 0.550 +/- 0.044 to 0. 754 +/- 0.071. Also, the absorption rate constant increased from 0. 199 +/- 0.045 to 0.276 +/- 0.059 min-1 due to alcohol coadministration; however, this increase was not significant. Alcohol inhibition of cocaine metabolism caused an increase in cocaine elimination half-life from 26.3 +/- 3.6 to 40.0 +/- 8.1 min. Also, cocaine tissue distribution was enhanced by alcohol, resulting in a significant increase in cocaine volume of distribution. Analysis of the brain cocaine concentration-neurochemical effect relationship by the sigmoid-Emax pharmacodynamic model showed that Emax increased from 850 +/- 200 to 1550 +/- 640% of baseline due to alcohol coadministration, whereas EC50 decreased from 3400 +/- 580 to 2000 +/- 650 ng/mL, indicating higher cocaine potency in the presence of alcohol. The estimates of the indirect inhibitory pharmacodynamic model used to examine the plasma cocaine concentration-change in blood pressure relationship were not significantly different after the two treatments. These results indicate that alcohol significantly alters cocaine absorption, distribution, and elimination, resulting in higher and prolonged cocaine plasma concentration. Alcohol coadministration also potentiates the neurochemical response to cocaine administration.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Cocaine and alcohol interactions in the rat: Effect on cocaine pharmacokinetics and pharmacodynamics

Pan

Hedaya

1999

Journal of Pharmaceutical Sciences

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Alcohol and Drug Interactions

Jones¹

2004

Handbook of Drug Interactions

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Acute care for alcohol intoxication

Yost¹

2002

Postgraduate Medicine

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The clinical assessment of an acutely intoxicated patient should be performed with meticulous care and include repetitive examinations to properly determine the patient's condition. Multiple factors, such as trauma and concomitant use of other drugs, can confuse the diagnostic picture and affect the choice of therapy. In this article, Dr Yost reviews the diagnostic considerations, appropriate treatment, and clinic discharge for the intoxicated patient.

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Interaction of Alcohol With Therapeutic Drugs and Drugs of Abuse

Cited by 3 publications

References 174 publications

Cocaine and alcohol interactions in the rat: Effect on cocaine pharmacokinetics and pharmacodynamics

Cocaine and alcohol interactions in the rat: Effect on cocaine pharmacokinetics and pharmacodynamics

Alcohol and Drug Interactions

Acute care for alcohol intoxication

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