An intravenous anesthetic agent which has the advantage of a very rapid onset after infusion or bolus injection plus a very short recovery period of a couple of minutes. (From Smith and Reynard, Textbook of Pharmacology, 1992, 1st ed, p206). Propofol has been used as ANTICONVULSANTS and ANTIEMETICS.
Propofol is an intravenous anaesthetic agent used for induction and maintenance of general anaesthesia. IV administration of propfol is used to induce unconsciousness after which anaesthesia may be maintained using a combination of medications. Recovery from propofol-induced anaesthesia is generally rapid and associated with less frequent side effects (e.g. drowsiness, nausea, vomiting) than with thiopental, methohexital, and etomidate. Propofol may be used prior to diagnostic procedures requiring anaesthesia, in the management of refractory status epilepticus, and for induction and/or maintenance of anaesthesia prior to and during surgeries.
Top Gene Interactions
- Metabolism: Propofol is rapidly distributed into peripheral tissues after absorption. It is highly protein bound in vivo and is metabolised by conjugation in the liver. Propofol is metabolized mainly by glucuronidation by uridine diphosphate-glucuronosyltransferases (UGTs) and by hydroxylation by CYP2B6 and CYP2C enzymes. The enzymes SULT1A1 and NQO1 participate in later steps in propofol metabolism. An unidentified route of extrahepatic metabolism may also exist, suggested by the fact that propofol clearance exceeds estimated hepatic blood flow. (L1002, A600, A304). Propofol is hepatically metabolized mainly by glucuronidation at the C1-hydroxyl. Hydroxylation of the benzene ring to 4-hydroxypropofol may also occur via CYP2B6 and 2C9 with subsequent conjugation to sulfuric and/or glucuronic acid. Hydroxypropofol has approximately 1/3 of hypnotic activity of propofol. Route of Elimination: It is chiefly eliminated by hepatic conjugation to inactive metabolites which are excreted by the kidney. Half Life: Initial distribution phase t1/2α=1.8-9.5 minutes. Second redistirubtion phase t1/2β=21-70 minutes. Terminal elimination phase t1/2γ=1.5-31 hours.
- Uses/Sources: Its widespread use as an anesthetic induction agent has largely replaced that of sodium pentothal. It is also commonly used in veterinary medicine. (L1002). Used for induction and/or maintenance of anaesthesia and for management of refractory status epilepticus.
- Health Effects: Mild myoclonic movements are common, as with other intravenous hypnotic agents. 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. Overdose of these agents is likely to cause cardiorespiratory depression. (L1002, L1160) They cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive. May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
- Symptoms: 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. A more serious but rare side effect is dystonia.
- Treatment: If overdosage occurs, Propofol administration should be discontinued immediately. Overdosage is likely to cause cardiorespiratory depression. Respiratory depression should be treated by artificial ventilation with oxygen. Cardiovascular depression may require repositioning of the patient by raising the patient's legs, increasing the flow rate of intravenous fluids, and administering pressor agents and/or anticholinergic agents. (L1712)
- Route of Exposure: Rapid - time to onset of unconsciousness is 15-30 seconds, due to rapid distribution from plasma to the CNS. Distribution is so rapid that peak plasma concentrations cannot be readily measured. Duration of action is 5-10 minutes. Parenteral (intravenous injection) (L1002); inhalation (L1002) ; dermal (L1002)
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: IV LD<sub>50</sub>=53 mg/kg (mice), 42 mg/kg (rats). Oral LD<sub>50</sub> (as a solution in soybean oil)=1230 mg/kg (mice), 600 mg/kg (rats)
Mechanism of Action
|Target Name||Mechanism of Action||References|
Gamma-aminobutyric acid receptor subunit beta-2
Gamma-aminobutyric acid receptor subunit beta-3
Carbonic anhydrase 1
Carbonic anhydrase 2
Sodium channel protein type 2 subunit alpha
Sodium channel protein type 4 subunit alpha
Nuclear receptor subfamily 1 group I member 2
GABA-A receptor (anion channel)
Gamma-aminobutyric acid receptor subunit alpha-1
Fatty-acid amide hydrolase 1
|The action of propofol involves a positive modulation of the inhibitory function of the neurotransmitter gama-aminobutyric acid(GABA) through GABA-A receptors.||
Propofol Interacts with Diseases
|Disease||Inference Score||References/Inference Genes|
|Diabetes Mellitus, Experimental||34.81||
|Diabetes Mellitus, Type 2||24.98|
|Radiation Injuries, Experimental||23.88|
|Cell Transformation, Neoplastic||20.9|
|Myocardial Reperfusion Injury||20.57|
|Infarction, Middle Cerebral Artery||18.25|
|Alcoholic liver cirrhosis||17.69|