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Propofol

Written by: Editorial Staff.

Propofol, marketed as Diprivan by AstraZenica, was originally developed in the UK by Imperial Chemical Industries. Clinical trials commenced in 1977, using a form solubilized in cremephor EL. Due to allergic reactions, to cremophor, this formulation was withdrawn from the market. A combination formula was reintroduced in 1986 by AstraZenica under the brand name Diprivan (diisopropyl intravenous anesthetic).

A currently available preparation is 1% propofol, 10% soy bean oil, and 1.2% purified egg phospholipid (an emulsifier), with 2.25% of glycerol as a tonicity-adjusting agent, and sodium hydroxide to adjust the pH. A water-soluble pro-drug form, fospropofol, has recently been developed and tested with positive results. Marketed as Lusedra, this new form may not produce the pain at injection site that often occurs with the traditional form of the drug. The FDA approved the product in 2008. Currently, Propofol is approved for use in more than 50 countries, and generic versions are available.

Classifications

Propofol is a short-acting, intravenously administered hypnotic sedative agent, general anesthetic, and anesthesia adjunct. Propofol is not considered a pain reliever, so opioids, such as Fentanyl, may be combined with Propofol to alleviate pain.

In October of 2009, fospropofol, the pro-drug form of propofol which is converted into propofol in the liver, was added to the list of controlled substances as a Schedule IV drug in the United States, given that since it is converted to propofol in the blood stream, and because of its potential for abuse and addiction, fospropofol was also a potential drug of abuse and addiction. Propofol, which has been on the market since the late 1980′s, is not a controlled substance.

Uses

Propofol is used for the induction and maintenance of anesthesia, sedation for mechanically ventilated adults, and procedural sedation for endoscopic procedures. It is also used in veterinary medicine. In critically ill patients it has been found to be superior to Lorazepam both in effectiveness cost; therefore, the use of propofol is now encouraged, whereas the use of Lorazepam is discouraged.

Propofol is also used for recreational purposes. Misuse has been reported to be more common among anesthetics on rotations with short rest periods, as recreational users report awakening to a well-rested state. Recreational use of the Propofol is rare due to its potency and the level of supervision required to consume it safely.

Effects

Propofol users show great variability in their response to the drug, sometimes experiencing extreme sedation with small doses. Propofol is used to reduce anxiety and tension, as well as to promote relaxation and sleep. Propofol is also used to promote a loss of consciousness or loss of awareness for short diagnostic tests and surgical procedures. Short-term effects of Propofol include mild euphoria, hallucinations, and disinhibition. Long-term use of the drug has been reported to result in addiction.

Side Effects of Propofol Include:

  • Difficulty breathing
  • Wheezing
  • Swelling of the throat
  • Fast heartbeat
  • Palpitations
  • Lightheadedness or fainting spells
  • Numbness or tingling in the hands or feet
  • Seizure
  • Skin rash
  • Flushing
  • Itching
  • Swelling or extreme pain at the injection site
  • Uncontrollable muscle spasm.

Adverse effects of Propofol include low blood pressure, transient apnea, pain on injection; dystonia, mild myoclonic movements, and malignant hyperpyrexia. Propofol has also triggered priapism in some patients. Another rare, but serious side effect of Propofol is Propofol Infusion Syndrome, a potentially lethal metabolic derangement that has been reported in critically ill patients after a prolonged use of high-doses of Propofol in combination with catecholamines and/or corticosteroids.

Similar Drugs

Other Schedule IV drugs like Propofol include benzodiazepines (Valium, Xanax, Versed) and barbiturates (Sodium Pentathol).

Addiction Information

Long-term use of the Propofol has been reported to result in addiction. Warning signs of addiction to Propofol may include disinhibition, euphoria, sedation; mood changes, habit changes, changes in sleep habits; detachment from family and friends, unreliability and absence from obligations, unpleasant physical and emotional feelings after the drug’s effects wear off; decrease in funds, unkempt physical appearance, and inappropriate sexual behavior.

Propofol Withdrawal

Propofol has been known to cause withdrawal symptoms after abrupt cessation of long time use. It is also possible for withdrawal symptoms to occur when Propofol has only been consumed for one to two weeks. Withdrawal symptoms of Propofol include unpleasant feelings, sweating, nausea; fatigue, insomnia, irritability; stomach cramps, panic attacks, vomiting; tremors and seizures.

Overdose

In order for a Propofol overdose to occur, a dosage in excess of 200mg is required. Considering a state of sedation or anesthesia is achieved after just 40mg, a self-induced overdose is quite unlikely. The high dose-response curve of the drug makes potential misuse very dangerous without proper monitoring, and at least three deaths from self-administration have been recorded. As with any other general anesthetic, Propofol should be administered only where highly trained staff and facilities for monitoring are available, as well as proper airway management (supply of supplemental oxygen, artificial ventilation and cardiovascular resuscitation).

The respiratory effects of Propofol are strengthened by other respiratory depressants, such as benzodiazepines. Attention to the risks of non-medical use of Propofol came into focus in August of 2009, due to the Los Angeles County coroner’s conclusion that pop singer Michael Jackson died from a combination of Propofol and Lorazepam, a benzodiazepine.