Propofol , marketed as Diprivan among others, is a short-term drug that results in a decrease in the level of awareness and lack of memory for the event. Its use includes starting and maintenance of general anesthesia, sedation for adults with mechanical ventilation, and procedural sedation. It is also used for epileptic status if other drugs do not work. This is given by injection into a blood vessel. The maximum effect takes about two minutes and usually lasts five to ten minutes.
Common side effects include irregular heartbeat, low blood pressure, burning sensation at the injection site, and stop breathing. Other serious side effects may include seizures, infections with improper use, addiction, and propofol infusion syndrome with prolonged use. It seems safe to use during pregnancy but has not been well studied in this group. However, it is not recommended during cesarean section. Propofol is not a painkiller, so opioids like morphine can also be used. Whether or not they are always needed is not clear. Propofol is believed to work at least partly through receptors for GABA.
Propofol was discovered in 1977 and approved for use in the United States in 1989. It is a List of Essential Medicines of the World Health Organization, the most effective and safe medicines needed in the health system. It is available as a generic drug. Wholesale prices in developing countries are between 0.61 and 8.50 USD per bottle. It has been referred to as milk amnesia (playing on milk magnesia) because of its milk-like appearance from intravenous preparations. Propofol is also used in veterinary medicine.
Video Propofol
Medical use
Anesthesia
Propofol is used for induction and maintenance (in some cases) general anesthesia, after replacing sodium thiopental. It may also be provided as part of an anesthetic maintenance technique called total intravenous anesthesia using manually programmed infusion pumps or computer-controlled infusion pumps in a process called controlled infusion target or TCI. Propofol is also used to calm individuals who receive mechanical ventilation but do not undergo surgery, such as patients in the intensive care unit. In critically ill patients, propofol is found to be superior to lorazepam both in overall effectiveness and cost.
Propofol is often used as a substitute for sodium thiopental to initiate anesthesia because recovery from propofol is faster and "clear."
procedural sedation
Propofol is also used for procedural sedation. Its use in this setting results in a faster recovery compared to midazolam. It can also be combined with opioids or benzodiazepines. Because of its rapid induction and recovery time, propofol is also widely used for the sedation of infants and children undergoing MRI. It is also often used in combination with ketamine as both have lower levels of side effects.
Maps Propofol
Other uses
Execution
The Missouri Supreme Court decided to allow the use of propofol to execute sentenced prisoners. However, the first execution by propofol lethal dosing was discontinued on October 11, 2013 by governor Jay Nixon following threats from the European Union to restrict drug exports if used for that purpose. Britain has banned the export of pharmaceuticals or propofol-containing veterinary drugs to the United States.
Use of recreation
The use of recreational drugs through self-administration has been reported, but is relatively rare because of its potential and the level of monitoring required for safe use. Critically, steep dose-response curves make recreational use of propofol extremely dangerous, and mortality from self-administration continues to be reported. Short-term effects sought through recreational use include mild euphoria, hallucinations, and disinhibition.
The use of recreational drugs has been described among medical staff, such as anesthesiologists who have access to drugs, and is reported to be more common among anesthesiologists on rotations with short rest periods (such as awakening is a considerable resting state). Long-term use has been reported to cause addiction.
Attention to the risks of off-label propofol use increased in August 2009 due to the Los Angeles County coroner's conclusion that the Michael Jackson music icon died from a mixture of propofol and drugs benzodiazepine lorazepam, midazolam and diazepam on June 25, 2009. According to a search warrant 22 In July 2009, which was not sealed by Harris County District Court, Texas, Jackson's private doctor, Conrad Murray, gave 25 milligrams of propofol diluted with lidocaine shortly before Jackson's death. Even so, in 2016 propofol is not on the schedule of the US Drug Abuse Administration.
Side effects
One of the most common side effects of propofol is pain when injected, especially in smaller blood vessels. This pain arises from the activation of pain receptors, TRPA1, found in the sensory nerves and can be reduced by pretreatment with lidocaine. Less pain is experienced when infused at a slower rate in the large vein (antecubital fossa). Patients exhibit great variability in their response to propofol, occasionally indicating deep sedation with small doses.
Additional side effects include low blood pressure associated with vasodilation, temporary apnea after induction dose, and cerebrovascular effects. Propofol has a clearer hemodynamic effect compared to many intravenous anesthetic agents. Reports of 30% or more blood pressure decrease are considered at least in part due to inhibition of sympathetic nerve activity. This effect is related to the dose and level of administration of propofol. This may also be amplified by opioid analgesics. Propofol may also cause decreased systemic vascular resistance, myocardial blood flow, and oxygen consumption, possibly through direct vasodilation. There are also reports that may cause a green change in urine.
As a respiratory depressant, propofol often produces apnea. Persistent apnea can depend on factors such as premedication, dosage, and degree of administration, and can sometimes last for more than 60 seconds. Perhaps as a result of depression from central inspiratory movements, propofol can produce significant reductions in respiratory rate, minute volume, tidal volume, average inspiratory flow rate, and functional residual capacity.
Reduced cerebral blood flow, brain metabolic oxygen consumption, and intracranial pressure are also characteristic of propofol administration. In addition, propofol can reduce intraocular pressure by as much as 50% in patients with normal intraocular pressure.
A more serious but rare side effect is dystonia. Mild myoclonic movements often occur, as do other intravenous hypnotic agents. Propofol appears to be safe for use in porphyria, and is not known to trigger malignant hyperpirexia.
Propofol has also been reported to induce priapism in some individuals, and has been observed to suppress the REM sleep stage and worsen poor sleep quality in some patients.
Like other general anesthesia agents, propofol should be administered only if appropriate staff and trained facilities for monitoring are available, as well as appropriate airway management, supplemental oxygen supply, artificial ventilation, and cardiovascular resuscitation.
Propofol infusion syndrome
Another rare, but serious, side effect is the propofol infusion syndrome. This potentially deadly metabolic disorder has been reported in critically ill patients after prolonged infusion of high-dose substances in combination with catecholamines and/or corticosteroids.
CBS genetic defects
People with this gene have difficulty processing sulfites (one of the potential materials).
Interactions
Respiratory breathing effects increase when administered with other respiratory depressants, including benzodiazepines.
Action mechanism
Propofol has been proposed to have several mechanisms of action, either through the potentiation of GABA receptor activity A and therefore acting as GABA A positive allosteric modulator receptor, thus slowing the duct-time closure, and at high doses, propofol may activate GABA receptor A in the absence of GABA, behave as a GABA receptor agonist A as well.. Propofol analogues have been shown to also act as sodium channel blockers. Some studies also suggest that the endocannabinoid system may contribute significantly to the action of propofol anesthesia and its unique properties. EEG studies in those undergoing general anesthesia with propofol found that it led to a significant reduction in the capacity of brain information integration at the frequency of gamma waves.
Researchers have identified sites in which propofol binds to the GABA receptor A in the brain, at the second transmembrane domain of the beta subunit of the GABA receptor A .
Pharmacokinetics
Propofol is strongly bound to the protein in vivo and is metabolized by conjugation in the liver. The half-life of propofol elimination has been estimated between 2 and 24 hours. However, the duration of its clinical effects is much shorter, as propofol is distributed rapidly to peripheral tissues. When used for IV sedation, a single dose of propofol usually disappears within minutes. Propofol versatile; drugs may 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 drugs. This characteristic of rapid onset and recovery along with its amnestic effects has led to widespread use for sedation and anesthesia.
Chemistry
Propofol was originally developed in England by Imperial Chemical Industries as ICI 35868. Clinical trials followed in 1977, using a soluble form in EL cremophor. However, due to anaphylactic reactions to cremophore, this formulation is withdrawn from the market and then reformulated as an oil/propofol mixture in water. The emulsion formulation was re-launched in 1986 by ICI (now AstraZeneca) under the Diprivan brand name. The currently available preparations are 1% propofol, 10% soybean oil, and egg phospholipid 1.2% purified as emulsifiers, with 2.25% glycerol as the tonisity regulator, and sodium hydroxide to adjust the pH. Diprivan contains EDTA, a common chelation agent, which also acts on its own (bacteriostatic to some bacteria) and synergistically with several other antimicrobial agents. Newer generic formulations contain sodium metabisulfite or benzyl alcohol as an antimicrobial agent. Propofol emulsion is a very opaque white liquid due to light scattering from tiny (about 150-nm) oil droplets it contains.
The water-soluble prodrug form, fospropofol, has recently been developed and tested with positive results. Fospropofol is rapidly broken down by the enzyme alkaline phosphatase to form propofol. Marketed as Lusedra, this new formulation may not produce pain at injection sites that often occur with traditional forms of medicine. The US Food and Drug Administration approved the product in 2008. However, fospropofol is a Schedule IV controlled substance with DEA ​​ACSCN in 2138 in the United States unlike propofol.
Recent developments
With the incorporation of the azobenzene unit, a version of photofol (AP2) version that can be downloaded in 2012 that allows optical control of GABA receptors A by light. In 2013, the propofol binding site at GABA mammal recipes A has been identified by photolabeling using a Diazirine derivative. In addition, it is shown that hyaluronan polymers present in synovia can be protected from free synovia by propofol.
Propofol is one of the chemicals used in the manufacture of avasimibe of the drug under study.
References
External links
- The Diprivan website is run by AstraZeneca
- Detailed pharmacy information
- US. National Medical Library: Drug Information Portal - Propofol
Source of the article : Wikipedia
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