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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/12/24 05:06:24」(JST)
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Not to be confused with Profadol.
| Systematic (IUPAC) name | |
|---|---|
| 2,6-diisopropylphenol | |
| Clinical data | |
| Pregnancy cat. |
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| Legal status |
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Dependence
liability |
Moderate |
| Routes | Intravenous |
| Pharmacokinetic data | |
| Bioavailability | NA |
| Protein binding | 95 to 99% |
| Metabolism | Hepatic glucuronidation |
| Half-life | 30 to 60 min |
| Excretion | Hepatic |
| Identifiers | |
| CAS number | 2078-54-8 Y |
| ATC code | N01AX10 |
| PubChem | CID 4943 |
| DrugBank | DB00818 |
| ChemSpider | 4774 Y |
| UNII | YI7VU623SF Y |
| KEGG | D00549 Y |
| ChEBI | CHEBI:44915 Y |
| ChEMBL | CHEMBL526 Y |
| Chemical data | |
| Formula | C12H18O |
| Mol. mass | 178.271 g/mol |
|
SMILES
|
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InChI
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| Y (what is this?) (verify) | |
Propofol (INN, marketed as Diprivan by Fresenius Kabi) is a short-acting, intravenously administered hypnotic/amnestic agent. Its uses include the induction and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. Propofol is also commonly used in veterinary medicine. It is approved for use in more than 50 countries, and generic versions are available.
Chemically, propofol is not related to barbiturates and has largely replaced sodium thiopental (Pentothal) for induction of anesthesia because recovery from propofol is more rapid and "clear" when compared with thiopental. Propofol is not considered an analgesic, so opioids such as fentanyl may be combined with propofol to alleviate pain.[1] Propofol has been referred to as milk of amnesia (a play on words of milk of magnesia), because of the milk-like appearance of its intravenous preparation.[2] It is on the WHO Model List of Essential Medicines, the most important medications needed in a health system.[3]
Contents
- 1 Medical uses
- 2 Other uses
- 2.1 Executions
- 2.2 Recreational use
- 3 Adverse effects
- 3.1 Propofol infusion syndrome
- 4 Contraindications and interactions
- 5 Chemistry
- 6 Mechanism of action
- 7 Pharmacokinetics
- 8 Supply issues
- 9 Recent developments
- 10 References
- 11 External links
Medical uses
Propofol is used for induction and maintenance (in some cases) of anesthesia, having largely replaced sodium thiopental for this indication.[1] It can also be administered as part of an anaesthesia maintenance technique called total intravenous anaesthesia using either manually-programmed infusion pumps or computer-controlled infusion pumps in a process called target controlled infusion or TCI. Propofol is also used to sedate individuals who are receiving mechanical ventilation but are not undergoing surgery, such as patients in the intensive care unit. In critically ill patients, propofol has been found to be superior to lorazepam both in effectiveness and overall cost.[4] Propofol is also used for procedural sedation, for example during endoscopic procedures. Its use in these settings results in a faster recovery compared to midazolam.[5] Because of its fast induction and recovery time, propofol is also widely used for sedation of infants and children undergoing MRI.[6]
Other uses
Executions
The Missouri Supreme Court decided to allow the use of propofol to execute prisoners condemned to death. However, the first execution by administration of a lethal dose of propofol was halted on 11 October 2013 by governor Jay Nixon following threats from the European Union to limit the drug's export if it were used for that purpose.[7][8]
Recreational use
Recreational use of the drug via self-administration has been reported[9][10] (including among medical professionals, see below), but is relatively rare due to its potency and the level of monitoring required for safe use.[citation needed] Critically, the steep dose-response curve of the drug makes potential misuse very dangerous without proper monitoring, and deaths from self-administration continue to be reported.[11][12]
The short-term effects sought via recreational use include mild euphoria, hallucinations, and disinhibition.[13][14] The euphoria caused by propofol has been reported to be unlike that caused by other sedation agents; as one anesthetist reported, "I... remember my first experience using [administering] propofol: a young woman... emerging from a MAC anesthesia looked at me as though I were a masked Brad Pitt and told me that she felt simply wonderful."[15]
Recreational use of the drug has been described amongst medical staff, such as anesthetists who have access to the drug,[16] and is reportedly more common among anesthetists on rotations with short rest periods (as rousing is to a well-rested state).[17] Long-term use has been reported to result in addiction.[16][18]
Attention to the risks of off-label use of propofol increased in August 2009 due to the Los Angeles County coroner's conclusion that music icon Michael Jackson died from a mixture of propofol and the benzodiazepine drugs lorazepam and diazepam.[19][20][21][22] According to a 22 July 2009 search warrant affidavit unsealed by the district court of Harris County, Texas, Jackson's personal physician, Conrad Murray, administered 25 milligrams of propofol diluted with lidocaine shortly before Jackson's death.[20][21][23] Even so, as of 2009 propofol was not on a U.S Drug Enforcement Administration schedule.[17][24]
Adverse effects
One of propofol's most frequent side effects is pain on injection, especially in smaller veins. This pain arises from activation of the pain receptor, TRPA1,[25] found on sensory nerves and can be mitigated by pretreatment with lidocaine.[26] Empirically, less pain is experienced when infused at a slower rate in a large vein (antecubital fossa). Patients show great variability in their response to propofol, at times showing profound sedation with small doses.
Additional side effects include low blood pressure related to vasodilation, transient apnea following induction doses, and cerebrovascular effects. Propofol has more pronounced hemodynamic effects relative to many intravenous anesthetic agents.[27] Reports of blood pressure drops of 30% or more are thought to be at least partially due to inhibition of sympathetic nerve activity.[28] This effect is related to dose and rate of propofol administration. It may also be potentiated by opioid analgesics.[29] Propofol can also cause decreased systemic vascular resistance, myocardial blood flow, and oxygen consumption, possibly through direct vasodilation.[30]
As a respiratory depressant, propofol frequently produces apnea. The persistence of apnea can depend on factors such as premedication, dose administered, and rate of administration, and may sometimes persist for longer than 60 seconds.[31] Possibly as the result of depression of the central inspiratory drive, propofol may produce significant decreases in respiratory rate, minute volume, tidal volume, mean inspiratory flow rate, and functional residual capacity.[27]
Diminishing cerebral blood flow, cerebral metabolic oxygen consumption, and intracranial pressure are also characteristic of propofol administration.[32] In addition, propofol may decrease intraocular pressure by as much as 50% in patients with normal intraocular pressure.[33]
A more serious but rare side effect is dystonia.[34] 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.[citation needed]
Finally, propofol is also reported to induce priapism in some individuals,[35][36] and has been observed to suppress REM sleep stage and to worsen the poor sleep quality in some patients.[37]
Propofol infusion syndrome
Main article: Propofol infusion syndrome
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 substance in combination with catecholamines and/or corticosteroids.[38]
Contraindications and interactions
The respiratory effects of propofol are potentiated by other respiratory depressants, including benzodiazepines.[39] As with any other general anesthetic agent, propofol should be administered only where appropriately trained staff and facilities for monitoring are available, as well as proper airway management, a supply of supplemental oxygen, artificial ventilation, and cardiovascular resuscitation.[40]
Chemistry
A 20-ml ampoule of 1% propofol emulsion, as sold in Australia by Sandoz
Propofol was originally developed in the UK by Imperial Chemical Industries as ICI 35868. Clinical trials followed in 1977, using a form solubilised in cremophor EL. However, due to anaphylactic reactions to cremophor, this formulation was withdrawn from the market and subsequently reformulated as an emulsion of a soya oil/propofol mixture in water. The emulsified formulation was relaunched in 1986 by ICI (now AstraZeneca) under the brand name Diprivan. The currently available preparation is 1% propofol, 10% soybean oil, and 1.2% purified egg phospholipid as an emulsifier, with 2.25% glycerol as a tonicity-adjusting agent, and sodium hydroxide to adjust the pH. Diprivan contains EDTA, a common chelation agent, that also acts alone (bacteriostatically against some bacteria) and synergistically with some other antimicrobial agents. Newer generic formulations contain sodium metabisulfite or benzyl alcohol as antimicrobial agents. Propofol emulsion is a highly opaque white fluid due to the scattering of light from the tiny (about 150-nm) oil droplets it contains.
A 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 the pain at injection site that often occurs with the traditional form of the drug. The US Food and Drug Administration approved the product in 2008.[41]
Mechanism of action
Propofol has been proposed to have several mechanisms of action,[42][43][44] both through potentiation of GABAA receptor activity, thereby slowing the channel-closing time,[45][46][47] and also acting as a sodium channel blocker.[48][49] Recent research has also suggested that the endocannabinoid system may contribute significantly to propofol's anesthetic action and to its unique properties.[50] EEG research upon those undergoing general anesthesia with propofol finds that it causes a prominent reduction in the brain's information integration capacity at gamma wave band frequencies.[51]
Researchers have identified the site where propofol binds to GABAA receptors in the brain, on the second transmembrane domain of the beta subunit of the GABA A[52]
Pharmacokinetics
Propofol is highly protein-bound in vivo and is metabolised by conjugation in the liver.[53] The half-life of elimination of propofol has been estimated to be between 2 and 24 hours. However, its duration of clinical effect is much shorter, because propofol is rapidly distributed into peripheral tissues. When used for IV sedation, a single dose of propofol typically wears off within 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[54] have led to its widespread use for sedation and anesthesia.
Supply issues
On 4 June 2010, Teva Pharmaceutical Industries Ltd., an Israel-based pharmaceutical firm and a major supplier of the drug, announced the firm would no longer manufacture it. This aggravates an already existing shortage, caused by manufacturing difficulties at Teva and Hospira. A Teva spokesperson attributed the halt to ongoing process difficulties, and a number of pending lawsuits related to the drug.[55] In Switzerland, various preparations of the drug are supplied by Fresenius-Kabi, a German company.
Recent developments
By incorporation of an azobenzene unit, a photoswitchable version of propofol (AP2) was developed in 2012 that allows for optical control of GABAA receptors with light.[56] In 2013, a propofol binding site on mammalian GABAA receptors has been identified by photolabeling using a Diazirine derivative.[57] Additionally, it was shown that the hyaluronan polymer present in the synovia can be protected from free-radical depolymerization by propofol.[58]
References
- ^ a b Miner JR, Burton JH. Clinical practice advisory: Emergency department procedural sedation with propofol. Annals of Emergency Medicine. 2007 Aug;50(2):182–7, 187.e1. Epub 23 February 2007.
- ^ Euliano TY, Gravenstein JS (2004). "A brief pharmacology related to anesthesia". Essential anesthesia: from science to practice. Cambridge, UK: Cambridge University Press. p. 173. ISBN 0-521-53600-6. Retrieved 2 June 2009.
- ^ "WHO Model List of Essential Medicines" (PDF). World Health Organization. October 2013. p. 6. Retrieved 22 April 2014.
- ^ Cox, CE.; Reed, SD.; Govert, JA.; Rodgers, JE.; Campbell-Bright, S.; Kress, JP.; Carson, SS. (March 2008). "Economic evaluation of propofol and lorazepam for critically ill patients undergoing mechanical ventilation.". Crit Care Med 36 (3): 706–14. doi:10.1097/CCM.0B013E3181544248. PMC 2763279. PMID 18176312.
- ^ McQuaid, KR.; Laine, L. (May 2008). "A systematic review and meta-analysis of randomized, controlled trials of moderate sedation for routine endoscopic procedures.". Gastrointest Endosc 67 (6): 910–23. doi:10.1016/j.gie.2007.12.046. PMID 18440381.
- ^ Machata, AM; Willschke, H; Kabon, B; Kettner, SC; Marhofer, P (August 2008). "Propofol-based sedation regimen for infants and children undergoing ambulatory magnetic resonance imaging.". British journal of anaesthesia 101 (2): 239–43. doi:10.1093/bja/aen153. PMID 18534971.
- ^ Death Row Improvises, Lacking Lethal Mix, By RICK LYMAN, New York Times, 18 August 2013
- ^ After EU threats, Missouri halts execution by Propofol injection Al Jazeera America October 12th 2013
- ^ Riezzo I, Centini F, Neri M, Rossi G, Spanoudaki E, Turillazzi E, Fineschi V (2009). "Brugada-like EKG pattern and myocardial effects in a chronic propofol abuser". Clin Toxicol (Phila) 47 (4): 358–63. doi:10.1080/15563650902887842. PMID 19514884.
- ^ Belluck, Pam (6 August 2009). "With High-Profile Death, Focus on High-Risk Drug". New York Times. Retrieved 7 August 2009.
- ^ Iwersen-Bergmann S, Rösner P, Kühnau HC, Junge M, Schmoldt A (2001). "Death after excessive propofol abuse". International Journal of Legal Medicine 114 (4–5): 248–51. doi:10.1007/s004149900129. PMID 11355404.
- ^ Kranioti EF, Mavroforou A, Mylonakis P, Michalodimitrakis M. (22 March 2007). "Lethal self-administration of propofol (Diprivan): A case report and review of the literature". Forensic Science International 167 (1): 56–8. doi:10.1016/j.forsciint.2005.12.027. PMID 16431058.
- ^ In Sweetman SC (Ed.). Martindale: The Complete Drug Reference 2005. 34th Edn London pp. 1305–7
- ^ Baudoin Z. General anesthetics and anesthetic gases. In Dukes MNG and Aronson JK (Eds.). Meyler's Side Effects of Drugs 2000. 14th Edn Amsterdam pp. 330
- ^ C.F. Ward, 2008, Propofol: Dancing with a "White Rabbit", CSA Bulletin, pp. 61-63, accessed 24 November 2014.
- ^ a b Roussin A, Montastruc JL, Lapeyre-Mestre M (21 October 2007). "Pharmacological and clinical evidences on the potential for abuse and dependence of propofol: a review of the literature". Fundamental and Clinical Pharmacology 21 (5): 459–66. doi:10.1111/j.1472-8206.2007.00497.x. PMID 17868199.
- ^ a b Charatan F (2009). "Concerns mount over recreational use of propofol among US healthcare professionals". BMJ 339: b3673. doi:10.1136/bmj.b3673. PMID 19737827.
- ^ Bonnet U, Harkener J, Scherbaum N (June 2008). "A case report of propofol dependence in a physician". J Psychoactive Drugs 40 (2): 215–7. doi:10.1080/02791072.2008.10400634. PMID 18720673.
- ^ Moore, Solomon (28 August 2009). "Jackson’s Death Ruled a Homicide". New York Times.
- ^ a b Surdin, Ashley (25 August 2009). "Coroner Attributes Michael Jackson's Death to Propofol". The Washington Post. Retrieved 22 May 2010.
- ^ a b Itzkoff, Dave (24 August 2009). "Coroner's Findings in Jackson Death Revealed". The New York Times. Retrieved 22 May 2010.
- ^ "Jackson's Death: How Dangerous Is Propofol?". Time. 25 August 2009. Retrieved 22 May 2010.
- ^ http://www.scribd.com/doc/19058649/Michael-Jackson-search-warrant. Missing or empty
|title=(help) - ^ DEA may limit drug eyed in Jackson case. Associated Press. 15 July 2009.
- ^ "General anesthetics activate a nociceptive ion channel to enhance pain and inflammation". Pnas.org. Retrieved 8 June 2013.
- ^ "Propofol Drug Information, Professional". m drugs.com. Retrieved 2 January 2007.
- ^ a b Sebel PS, Lowden JD (1989). Propofol: a new intravenous anesthetic. Anesthesiology; 71(2):260-77.
- ^ Robinson B, Ebert T, O'Brien T, et al. Mechanisms whereby propofol mediates peripheral vasodilation in humans (1997). Anesthesiology; 86:64-72.
- ^ New awakening in anaesthesia—at a price. Lancet 1987; 8548: 1469-70.
- ^ Larijani G, Gratz I, Afshar M, et al. Clinical pharmacology of propofol: an intravenous anesthetic agent [published erratum appears in DICP 1990 Jan; 24: 102]. DICP 1989; 23: 743-9.
- ^ Langley M, Heel R. Propofol. A review of its pharmacodynamic and pharmacokinetic properties and use as an intravenous anaesthetic. Drugs 1988; 35: 334-72.
- ^ Bailey J, Mora C, Shafer S. Pharmacokinetics of propofol in adult patients undergoing coronary revascularization. Anesthesiology 1996; 84: 1288-97.
- ^ Reilly C, Nimmo W. New intravenous anaesthetics and neuromuscular blocking drugs. A review of their properties and clinical use. Drugs 1987; 34: 115-9.
- ^ Schramm BM, Orser BA (2002). Dystonic reaction to propofol attenuated by benztropine (Cogentin). Anesth Analg, 94, 1237–40.
- ^ Vesta, Kimi; Shaunta' Martina, Ellen Kozlowski (25 April 2009). "Propofol-Induced Priapism, a Case Confirmed with Rechallenge". The Annals of Pharmacotherapy 40 (5): 980–982. doi:10.1345/aph.1G555. PMID 16638914. Cite uses deprecated parameters (help);
|accessdate=requires|url=(help) - ^ Fuentes, Ennio; Silvia Garcia; Manuel Garrido; Cristina Lorenzo; Jose Iglesias; Juan Sola (July 2009). "Successful treatment of propofol-induced priapism with distal glans to corporal cavernosal shunt". Urology 74 (1): 113–115. doi:10.1016/j.urology.2008.12.066. PMID 19371930.
|accessdate=requires|url=(help) - ^ "Effects of propofol on sleep quality in mechanically ventilated critically ill patients: a physiological study - Eumorfia Kondili, Christina Alexopoulou, Nectaria Xirouchaki, Dimitris Georgopoulos". http://icmjournal.esicm.org/. Retrieved 2 October 2012.
- ^ Vasile B, Rasulo F, Candiani A, Latronico N (2003). "The pathophysiology of propofol infusion syndrome: a simple name for a complex syndrome". Intensive Care Medicine 29 (9): 1417–25. doi:10.1007/s00134-003-1905-x. PMID 12904852.
- ^ Doheny, Kathleen; Louise Chang; Hector Vila Jr (24 August 2009). "Propofol Linked to Michael Jackson's Death". WebMD. Retrieved 26 August 2009.
- ^ "AstraZeneca - United States Home Page". .astrazeneca-us.com. Retrieved 8 June 2013.
- ^ "Drugs@FDA: FDA Approved Drug Products". Accessdata.fda.gov. Retrieved 8 June 2013.
- ^ Trapani G, Altomare C, Liso G, Sanna E, Biggio G (February 2000). "Propofol in anesthesia. Mechanism of action, structure-activity relationships, and drug delivery". Curr. Med. Chem. 7 (2): 249–71. doi:10.2174/0929867003375335. PMID 10637364.
- ^ Kotani Y, Shimazawa M, Yoshimura S, Iwama T, Hara H. The experimental and clinical pharmacology of propofol, an anesthetic agent with neuroprotective properties. CNS Neuroscience and Therapeutics. 2008 Summer;14(2):95–106. doi:10.1111/j.1527-3458.2008.00043.x PMID 18482023
- ^ Vanlersberghe C, Camu F. Propofol. Handbook of Experimental Pharmacology. 2008;(182):227-52. doi:10.1007/978-3-540-74806-9_11 PMID 18175094
- ^ Trapani G, Latrofa A, Franco M, Altomare C, Sanna E, Usala M, Biggio G, Liso G. Propofol analogues. Synthesis, relationships between structure and affinity at GABAA receptor in rat brain, and differential electrophysiological profile at recombinant human GABAA receptors. Journal of Medicinal Chemistry. 21 May 1998;41(11):1846–54. doi:10.1021/jm970681h PMID 9599235
- ^ Krasowski MD, Jenkins A, Flood P, Kung AY, Hopfinger AJ, Harrison NL (April 2001). "General anesthetic potencies of a series of propofol analogs correlate with potency for potentiation of gamma-aminobutyric acid (GABA) current at the GABA(A) receptor but not with lipid solubility". J. Pharmacol. Exp. Ther. 297 (1): 338–51. PMID 11259561.
- ^ Krasowski MD, Hong X, Hopfinger AJ, Harrison NL. 4D-QSAR analysis of a set of propofol analogues: mapping binding sites for an anesthetic phenol on the GABA(A) receptor. Journal of Medicinal Chemistry. 18 July 2002;45(15):3210–21. doi:10.1021/jm010461a PMID 12109905
- ^ Haeseler G, Leuwer M (March 2003). "High-affinity block of voltage-operated rat IIA neuronal sodium channels by 2,6 di-tert-butylphenol, a propofol analogue". Eur J Anaesthesiol 20 (3): 220–4. doi:10.1017/s0265021503000371. PMID 12650493.
- ^ Haeseler G, Karst M, Foadi N, Gudehus S, Roeder A, Hecker H, Dengler R, Leuwer M. High-affinity blockade of voltage-operated skeletal muscle and neuronal sodium channels by halogenated propofol analogues. British Journal of Pharmacology. 2008 Sep;155(2):265-75. doi:10.1038/bjp.2008.255 PMID 18574460
- ^ Fowler CJ (February 2004). "Possible involvement of the endocannabinoid system in the actions of three clinically used drugs". Trends Pharmacol. Sci. 25 (2): 59–61. doi:10.1016/j.tips.2003.12.001.
- ^ Lee U, Mashour GA, Kim S, Noh GJ, Choi BM. (2009). Propofol induction reduces the capacity for neural information integration: implications for the mechanism of consciousness and general anesthesia. Conscious Cogn. 18(1):56–64.doi:10.1016/j.concog.2008.10.005 PMID 19054696
- ^ http://phys.org/news/2013-09-propofol-discovery-aid-anesthetics.html
- ^ Favetta P, Degoute C-S Perdrix J-P, Dufresne C, Boulieu R, Guitton J (2002). "Propofol metabolites in man following propofol induction and maintenance". British Journal of Anaesthesia 88 (5): 653–8. doi:10.1093/bja/88.5.653.
- ^ Veselis RA, Reinsel RA, Feshchenko VA, Wroński M (October 1997). "The comparative amnestic effects of midazolam, propofol, thiopental, and fentanyl at equisedative concentrations". Anesthesiology 87 (4): 749–64. doi:10.1097/00000542-199710000-00007. PMID 9357875.
- ^ "Teva won't make more of powerful sedative.".
- ^ Stein M, et al. (September 2012). "Azo-Propofols: Photochromic Potentiators of GABAA Receptors". Angewandte Chemie International Edition 51 (42): 15000–4. doi:10.1002/anie.201205475. PMID 22968919.
- ^ Yip G, Z.-W Chen, Edge C J, Smith E H, Dickinson R, Hohenester, E, Townsend R R, Fuchs K, Sieghart W, Evers A S, Franks N P (September 2013). "A propofol binding site on mammalian GABAAreceptors identified by photolabeling". Nature Chemical Biology 9 (11): 715–720. doi:10.1038/nchembio.1340.
- ^ Kvam C, Granese D, Flaibani A, Pollesello P, Paoletti S. (1993). "Hyaluronan can be protected from free-radical depolymerization by 2, 6-diisopropylphenol, a novel radical scavenger". Biochem. Biophys. Res. Comm. 193 (3): 927–33. doi:10.1006/bbrc.1993.1714. PMID 8391811.
External links
- Diprivan web site run by AstraZeneca
- Detailed pharmaceutical information
- U.S. National Library of Medicine: Drug Information Portal – Propofol
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UpToDate Contents
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- 1. 成人における処置時の鎮静 procedural sedation in adults
- 2. 腹部大動脈瘤ステントグラフト留置術に対する麻酔 anesthesia for endovascular aortic repair
- 3. 重症筋無力症患者に対する麻酔 anesthesia for the patient with myasthenia gravis
- 4. Intravenous anesthetic induction agents for adults
- 5. 小児に対する手術室外での鎮静処置に使用する薬剤 pharmacologic agents for pediatric procedural sedation outside of the operating room
English Journal
- Neonatal exposure to propofol affects BDNF but not CaMKII, GAP-43, synaptophysin and tau in the neonatal brain and causes an altered behavioural response to diazepam in the adult mouse brain.
- Ponten E, Fredriksson A, Gordh T, Eriksson P, Viberg H.SourceDepartment of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, Sweden.
- Behavioural brain research.Behav Brain Res.2011 Sep 30;223(1):75-80. Epub 2011 Apr 21.
- Animal studies have shown that neonatal anaesthesia is associated with acute signs of neurodegeneration and later behavioural changes in adult animals. The anaesthetic effect of propofol is thought to be mediated by γ-amino butyric acid (GABA)(A) receptors. The present study investigated the effect
- PMID 21540061
- [Safety and efficacy of continuous infusion propofol for diagnostic upper gastrointestinal endscopy in spontaneous breathing].
- Alados-Arboledas FJ, Millan-Bueno P, Exposito-Montes JF, de la Cruz-Moreno J, Perez-Parras A, Arevalo-Garrido A.SourceUnidad de Cuidados Intensivos Pediatricos, UGC Pediatria, Hospital Materno-Infantil de Jaen, Jaen, Espana.
- Anales de pediatria (Barcelona, Spain : 2003).An Pediatr (Barc).2011 Aug;75(2):124-8. Epub 2011 Mar 22.
- INTRODUCTION: Invasive procedures (IP) are an important reason for admision to PICU. Paediatric patients need a special anaesthetic approach and deep sedation is frequently required. The objective was to evaluate the safety and efficacy of continuous infusion propofol to achieve sedation for diagnos
- PMID 21429829
Japanese Journal
- 臨床経験 プロポフォールとケタミンによる全静脈麻酔の腎機能に与える影響 : フェンタニルまたはレミフェンタニルを併用した場合の比較
- 吉田 仁,工藤 倫之,澤田 匡宏 [他]
- 麻酔 61(8), 794-799, 2012-08
- NAID 40019402835
- Dexmedetomidine dose dependently decreases oral tissue blood flow during sevoflurane and propofol anesthesia in rabbits
- Sazuka S,Matsuura N,Ichinohe T
- Journal of oral and maxillofacial surgery 70(8), 1808-1814, 2012-08
- NAID 120004725196
Related Links
- Propofol was originally developed in the UK by Imperial Chemical Industries as ICI 35868. Clinical trials followed in 1977, using a form solubilised in cremophor EL. However, due to anaphylactic reactions to cremophor, this formulation ...
- Propofol official prescribing information for healthcare professionals. Includes: indications, dosage, adverse reactions, pharmacology and more. ... Neuroanesthesia Propofol injectable emulsion was studied in patients undergoing ...
Related Pictures
★リンクテーブル★
| リンク元 | 「プロポフォール」「麻酔」 |
| 拡張検索 | 「propofol infusion syndrome」 |
「プロポフォール」
特徴
構造
作用機序
薬理作用
- 鎮痛：× → 麻酔性鎮痛薬などと組み合わせて用いる。
- 意識消失：○
- 筋弛緩：△
- 反射抑制：○
効能又は効果
- 1%ディプリバン注
- 全身麻酔の導入及び維持
- 集中治療における人工呼吸中の鎮静
動態
- 1%ディプリバン注
- 1. 半減期は
- 日本人健康成人男子6例に1.0、2.0及び2.5mg/kgを単回静脈内ボーラス投与したとき、プロポフォールの体内動態は3-コンパートメントモデルに適合し、全血中濃度は3相性に減衰した。各相の半減期は2.6分(t1/2α)、51.0分(t1/2β)及び365分(t1/2γ)であった。中央コンパートメントにおける分布容積及び定常状態時の分布容積はそれぞれ26L及び317Lであった。全身クリアランス(CLTB)値は1.62L/分であった。1～2.5mg/kgの用量範囲で、血漿中薬物濃度－時間曲線下面積(AUC0-∞)が用量に比例して増加することが示された。また、薬物動態パラメータに明らかな性差はみられなかった（外国人の成績）。
- 2. 代謝及び排泄
- 成人患者8例に平均2.6mg/kgを単回静脈内ボーラス投与した場合、投与後24時間までにプロポフォール及び1,4キノール体のグルクロン酸抱合体ならびに1,4キノール体の硫酸抱合体として投与量の68.3%が尿中に排泄された。
- 3. 蛋白結合率6)
- 外国人患者にプロポフォールを2.5mg/kg用量で単回静脈内ボーラス投与したとき、投与後10及び120分後の蛋白結合率は約97～99%であった。
適応
注意
- 妊婦、授乳婦 → 母乳に移行する。ただし、その量は微々たるものらしい。しかし、できるだけ回避。
禁忌
- 1%ディプリバン注
- 1. 本剤又は本剤の成分に対し過敏症の既往歴のある患者
- 2. 妊産婦（「妊婦、産婦、授乳婦等への投与」の項参照）
- 3. 小児（集中治療における人工呼吸中の鎮静）
副作用
- 注射時の痛み、呼吸抑制、無呼吸、低血圧(麻酔導入時に起こる低血圧はバルビツレートに比べて高頻度に起こる)
- 徐脈-アシドーシス(プロポフォール注入症候群)：稀であるが致命的。
参考
- 1%ディプリバン注
「麻酔」
- 英
- anesthesia
- 関
- 麻酔機、術前準備
全身麻酔
1. Semi-rapid induction （成人の場合の基本）
- (a) モニター装着，静脈確保．
- (b) propofol（ 2 mg/kg ）remifentanil（ 0.5 μg/kg/min ）で入眠．
- (c) rocuronium（ 0.6 mg/kg ）で筋弛緩．
- (d) 100%酸素でBag & Mask
- (e) 麻酔が深くなったら気管挿管．
目的別の麻酔方法
- 心臓手術：on-pump CAB, off-pump CAB
- 肺手術：一側肺換気
- 産科麻酔：筋弛緩薬以外は胎盤を通過すると考えて良いと思われる。硬膜外麻酔でオピオイドを投与するのは分娩後。
- 帝王切開術：脊髄くも膜下麻酔
参考
- 1. 研修医用のマニュアル - 神戸大学大学院医学系研究科 外科系講座 麻酔科学分野
- 2. 麻酔科レジデントマニュアル 麻酔応用編 筑波大学附属病院麻酔科 2011 年ver.1.4