Metabolic Profiles of Propofol and Fospropofol: Clinical and Forensic Interpretative Aspects.

Ricardo Jorge Dinis-Oliveira

doi:10.1155/2018/6852857

Abstract

Propofol is an intravenous short-acting anesthetic widely used to induce and maintain general anesthesia and to provide procedural sedation. The potential for propofol dependency and abuse has been recognized, and several cases of accidental overdose and suicide have emerged, mostly among the health professionals. Different studies have demonstrated an unpredictable interindividual variability of propofol pharmacokinetics and pharmacodynamics with forensic and clinical adverse relevant outcomes (e.g., pronounced respiratory and cardiac depression), namely, due to polymorphisms in the UDP-glucuronosyltransferase and cytochrome P450 isoforms and drugs administered concurrently. In this work the pharmacokinetics of propofol and fospropofol with particular focus on metabolic pathways is fully reviewed. It is concluded that knowing the metabolism of propofol may lead to the development of new clues to help further toxicological and clinical interpretations and to reduce serious adverse reactions such as respiratory failure, metabolic acidosis, rhabdomyolysis, cardiac bradyarrhythmias, hypotension and myocardial failure, anaphylaxis, hypertriglyceridemia, renal failure, hepatomegaly, hepatic steatosis, acute pancreatitis, abuse, and death. Particularly, further studies aiming to characterize polymorphic enzymes involved in the metabolic pathway, the development of additional routine forensic toxicological analysis, and the relatively new field of ‘‘omics” technology, namely, metabolomics, can offer more in explaining the unpredictable interindividual variability.

Highlights

A general anesthetic is an unrecognizable chemical drug class that depresses all excitable tissues and produces a reversible state of unconsciousness, with absence of pain sensation over the entire body [1]
This study found no significant relationship between clinical differences and CYP2B6, GABRE, or other variants of the UGT1A9 gene [81]
Drugs with actions on the central nervous system are of particular importance in pharmacology, and major groups include anxiolytics, sedatives and hypnotics, antiepileptic, antipsychotics, antidepressant, antiparkinson, stimulants, general anesthetics, opioids, drugs for preventing or treating migraine, and miscellaneous drugs, including anticholinesterases, appetite suppressants, and centrally acting muscle relaxants

Summary

Introduction

A general anesthetic is an unrecognizable chemical drug class that depresses all excitable tissues and produces a reversible state of unconsciousness, with absence of pain sensation over the entire body [1]. Before the development of effective anesthetics and analgesics, as well as blood transfusions and antibiotics, successful major surgery was virtually impossible owing to the severe pain, hemorrhage, and infection; the patient was usually tied, held down, or rendered unconscious by hypoxia, concussion, or high doses of natural central nervous system depressants such as ethanol or opioids [2]. For a drug to be useful as a general anesthetic, its actions must be of rapid onset, effective during the duration of the surgical procedure, rapidly reversible. Only those that have short halflives and that can be continually administered are useful, which is not the case of ethanol, benzodiazepines, and the majority of barbiturates [2]. General anesthesia is usually induced by intravenous injection of anesthetic agent

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