Monday, July 27, 2009

The Cause of MJ's Death

Propofol (marketed under the trade name Diprivan) is a short-acting, intravenous, nonbarbiturate sedative agent used for the induction of general anesthesia for adults and children, maintenance of general anesthesia, sedation in medical contexts, such as intensive care unit (ICU) sedation for intubated, mechanically ventilated adults, and in procedures such as colonoscopy and endoscopy, as well as in dental surgery. It has largely replaced sodium thiopental (trade name Pentothal) for induction of anesthesia. Recovery after propofol anaesthesia is more rapid and 'clear' as compared to thiopental.

Typically during surgery, opioids such as fentanyl are also given since propofol is not considered an analgesic drug. Propofol is approved for use in more than 50 countries. It is also commonly used in veterinary medicine.

Propofol is highly protein bound in vivo and is metabolised by conjugation in the liver. Its rate of clearance exceeds hepatic blood flow, suggesting an extrahepatic site of elimination as well. It has several mechanisms of action, both through potentiation of GABA-A receptor activity, thereby slowing the channel closing time, and also acting as a sodium channel blocker. Recent research has also suggested the endocannabinoid system may contribute significantly to propofol's anesthetic action and to its unique properties.

The elimination half-life of propofol has been estimated to be between 2–24 hours. However, its duration of clinical effect is much shorter because propofol is rapidly distributed into peripheral tissues. When used for IV sedation, propofol typically wears off in minutes. Propofol is versatile; the drug can be given for short or prolonged sedation as well as for general anesthesia. Its use is not associated with nausea as is often seen with opioid medications. These characteristics of rapid onset and recovery along with its amnestic effects have led to its widespread use for sedation and anesthesia.

Side Effects
Aside from the hypotension (mainly through vasodilatation) and transient apnea following induction doses, one of propofol's most frequent side effects is pain on injection, especially in smaller veins. This pain can be mitigated by pretreatment with lidocaine. Patients tend to show great variability in their response to propofol, at times showing profound sedation with small doses. A more serious but rare side effect is dystonia. Mild myoclonic movements are common, as with other intravenous hypnotic agents. Propofol appears to be safe for use in porphyria, and has not been known to trigger malignant hyperpyrexia.

Another recently described rare, but serious, side effect is propofol infusion syndrome. This potentially lethal metabolic derangement has been reported in critically-ill patients after a prolonged infusion of high-dose propofol in combination with catecholamines and/or corticosteroids.

Despite a lack of analgesic properties, abuse of propofol has been reported. It can produce mild euphoria, sexual hallucinations, and disinhibition. Such recreational abuse has been described amongst medical staff such as anaesthetists who have access to the drug. However, abuse of the drug is relatively rare due to its potency and the level of monitoring required to take it, and it has not been scheduled by the US Drug Enforcement Administration. The steep dose response curve of the drug makes such abuse very dangerous without proper monitoring, and at least three deaths from self-administration have been recorded. The autopsy of entertainer Michael Jackson found propofol in his system and is believed to be a contributing factor in his death.

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