Pharmacokinetics and pharmacodynamics of intravenous midazolam in patients with severe alcoholic cirrhosis.
TLDR
Significant delay in the elimination of midazolam and decreased psychomotor function in patients with severe alcoholic liver disease is shown and Caution is needed in using this drug for premedication in such patients before endoscopy.Abstract:
Midazolam kinetics and psychomotor function were studied after an intravenous dose of 0.075 mg/kg body weight in seven patients with alcoholic cirrhosis and eight control patients. Four of the seven cirrhotics died of complications of their liver disease within six months of the study. The metabolism of midazolam was significantly impaired in the cirrhotic patients (p less than 0.025). These patients also had evidence of greater sedation than the control group for up to six hours after the dose was administered (p less than 0.05). The clearance of midazolam did not correlate significantly with the serum albumin, or bilirubin, or with the kinetics of antipyrine, or indocyanine green. This study shows significant delay in the elimination of midazolam and decreased psychomotor function in patients with severe alcoholic liver disease. Caution is needed in using this drug for premedication in such patients before endoscopy.read more
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Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult.
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References
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A physiological approach to hepatic drug clearance
TL;DR: The proposed classification of drug metabolism based on the hepatic extraction ratio allows prediction and interpretation of the effects of individual variations in drug‐metabolizing activity, route of administration, pharmacokinetic interactions, and disease states on hepatic drug elimination.
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The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function.
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The effects of age and liver disease on the disposition and elimination of diazepam in adult man.
TL;DR: The constancy of diazepam clearance indicates that drug plasma concentrations will not accumulate any more in the old than the young, and chronic dosage modifications based on pharmacokinetic considerations are unnecessary.
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Clearance concepts in pharmacokinetics
TL;DR: The kinetics of a drug eliminated by first-order processes in a perfusion-limited isolated perfused organ system are examined and the virtue of using clearance, instead of half-life, as a correlative parameter between these systems is stressed.
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Psychomotor Function and Psychoactive Drugs
TL;DR: A cursory review of the literature reveals that the techniques used to assess psychomotor functions are diverse, often complex, frequently insensitive to drug induced changes and sometimes inconvenient to enact or replicate.