Pharmacokinetics of haemoperfusion for drug overdose.
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Hemoperfusion↗
Biomedical subjects
N L Benowitz
Publications and source records attributed to N L Benowitz.
Pharmacokinetics of drug overdose.
Pharmacokinetics of drugs taken in overdose may differ from those observed following therapeutic doses. Differences are due both to dose-dependent changes and to effects of drugs or pathophysiological consequences of the overdose on kinetics. Dose-dependent changes in rate and extent of absorption, bioavailability (saturation of first-pass metabolism), distribution (saturation of protein binding sites) and metabolism are discussed. Gastrointestinal motility is affected both by specific drug actions, such as delayed gastric emptying by anticholinergic drugs, and by general nervous system depression caused by many drugs. Drug-induced circulatory insufficiency may retard tissue distribution and reduce clearance. Disturbances in blood and urine pH may alter distribution and clearance of weak acids and bases. Drug-induced renal or hepatic failure can significantly decrease clearance. Hypothermia is a common complication of drug overdose and might retard distribution and also reduce clearance. The data concerning pharmacokinetics during overdose are usually incomplete and difficult to interpret. Doses and times of ingestion are uncertain, duration of blood and urine sampling is often inadequate to distinguish absorption from distribution and elimination phases, active metabolites are not measured, protein binding is not determined and clinical features of patients not adequately described. We have, however, reviewed available data for salicylate, paracetamol (acetaminophen), barbiturates, ethchlorvynol, glutethimide, chloral hydrate, tricyclic antidepressants, lithium, phenytoin, ethanol, theophylline, digoxin, amphetamine and phencyclidine.
Acetaminophen↗
Nicotine and smokeless tobacco.
The following may be concluded about nicotine and smokeless tobacco use: Systemic absorption and levels of nicotine are similar in users of smokeless tobacco and cigarette smokers. Data from the few studies performed to date suggest that smokeless tobacco users develop a dependency similar to that for cigarette smokers. Effective treatment strategies to help smokeless tobacco users quit need to be developed. Smokeless tobacco use in young people also poses a concern for later development of dependence on cigarettes. The health hazards known to be caused by cigarette smoking and suspected to be related to chronic nicotine exposure are expected to be a hazard of habitual use of smokeless tobacco. A major concern in young males is accelerated coronary artery disease. Information about the potential health hazards of nicotine, as well as oral pathology, may be incorporated into educational programs to help discourage the use of smokeless tobacco, with a resultant decrease in the associated cancer risk.
Humans↗
Cardiotoxicity in the workplace.
A number of chemicals have been implicated in the causation of cardiovascular disease, although often in individual patients causality for any specific toxic exposure is difficult to establish. This review discusses toxic cardiovascular disease from specific toxins from the perspective of the types of injury and details epidemiology, mechanisms of toxicity, and clinical features. Discussed are carbon disulfide, carbon monoxide, organic nitrates, halogenated hydrocarbons, lead, cobalt, arsenic/arsine, and cadmium and antimony.
Cardiovascular Diseases↗
Disposition kinetics and metabolism of nicotine-1'-N-oxide in rabbits.
The disposition kinetics and metabolism of nicotine-1'-N-oxide (NNO) are of interest as the reduction of NNO might influence the pharmacokinetics of nicotine in tobacco users. The disposition kinetics of nicotine-1'-N-oxide were characterized in New Zealand rabbits. The clearance of NNO averaged 7.5 ml/min/kg. The half-life averaged 42.6 min and VDss was 0.34 liter/kg. The oral and ip bioavailabilities were 15.1 and 79%, respectively. NNO was reduced to nicotine and cotinine following i.v., oral, and ip injection. The pattern of metabolites after iv dosing suggests that there is systemic reduction of NNO, although the magnitude of that reduction is small, with less than 3% reduced to nicotine. Following oral NNO, 45% was reduced, with a metabolite pattern consistent with presystemic (bacterial or intestinal) metabolism.
Administration, Oral↗