WordNet
- a complex consisting of an organic base in association with hydrogen chloride
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/01/05 23:20:19」(JST)
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| Systematic (IUPAC) name | |||
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2-[(Dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol
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| Clinical data | |||
| Trade names | Ryzolt, Tramal, Ultram | ||
| AHFS/Drugs.com | monograph | ||
| MedlinePlus | a695011 | ||
| Licence data | US FDA:link | ||
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| Dependence liability |
Present[1] | ||
| Routes of administration |
Oral, IV, IM, rectal | ||
| Pharmacokinetic data | |||
| Bioavailability | 70–75% (oral), 77% (rectal), 100% (IM)[2] | ||
| Protein binding | 20%[3] | ||
| Metabolism | Liver-mediated demethylation and glucuronidation via CYP2D6 & CYP3A4[2][3] | ||
| Biological half-life | 6.3 ± 1.4 hr[3] | ||
| Excretion | Urine (95%)[4] | ||
| Identifiers | |||
| CAS Number | 27203-92-5 Y | ||
| ATC code | N02AX02 | ||
| PubChem | CID: 33741 | ||
| DrugBank | DB00193 Y | ||
| ChemSpider | 31105 Y | ||
| UNII | 39J1LGJ30J Y | ||
| KEGG | D08623 Y | ||
| ChEBI | CHEBI:9648 N | ||
| ChEMBL | CHEMBL1066 Y | ||
| Chemical data | |||
| Formula | C16H25NO2 | ||
| Molecular mass | 263.4 g/mol | ||
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Tramadol (marketed as Ultram, and as generics) is an opioid pain medication used to treat moderate to moderately severe pain.[1] When taken as an immediate-release oral formulation, the onset of pain relief usually occurs within about an hour.[5] It has two different mechanisms. First, it binds to the μ-opioid receptor. Second, it inhibits the reuptake of serotonin and norepinephrine.[6][7]
Serious side effects may include seizures, increased risk of serotonin syndrome, decreased alertness, and drug addiction.[1] The risk of serotonin syndrome appears to be low.[8] Common side effects include: constipation, itchiness and nausea, among others. A change in dosage may be recommended in those with kidney or liver problems. Its use is not recommended in women who are breastfeeding or those who are at risk of suicide.[1]
Tramadol is marketed as a racemic mixture of both R- and S-stereoisomers.[2] This is because the two isomers complement each other's analgesic activity.[2] It is often combined with paracetamol (acetaminophen) as this is known to improve the efficacy of tramadol in relieving pain.[2] Tramadol is metabolised to O-desmethyltramadol, which is a more potent opioid.[9] It is of the benzenoid class.
Tramadol was launched and marketed as Tramal by the German pharmaceutical company Grünenthal GmbH in 1977 in West Germany, and 20 years later it was launched in countries such as the UK, U.S., and Australia.[7]
Contents
- 1 Medical uses
- 1.1 Pregnancy and lactation
- 1.2 Labour and delivery
- 1.3 Children
- 1.4 Elderly
- 1.5 Liver and kidney failure
- 2 Adverse effects
- 2.1 Interactions
- 2.2 Contraindications
- 2.3 Overdose
- 2.4 Physical dependence and withdrawal
- 2.5 Psychological dependence and recreational use
- 2.6 Detection in biological fluids
- 3 Chemistry
- 3.1 Synthesis and stereoisomerism
- 4 Mechanism of action
- 5 Pharmacokinetics
- 6 Society and culture
- 6.1 Legal status
- 6.2 Brand names
- 7 Veterinary medicine
- 8 Pin cushion tree
- 9 Research
- 9.1 Investigational uses
- 10 See also
- 11 References
- 12 External links
Medical uses
Generic tramadol HCl tablets marketed by Amneal Pharmaceuticals.
Tramadol HCl for injection
Tramadol is used primarily to treat mild-severe pain, both acute and chronic.[10][11]
Tramadol is recommended for the management of pain in fibromyalgia by the European League Against Rheumatism.[12] Its analgesic effects take about one hour to come into effect and 2–4 hours to peak after oral administration with an immediate-release formulation.[10] On a dose-by-dose basis tramadol has about one-tenth the potency of morphine and is approximately equally potent when compared to pethidine and codeine.[13]
For pain moderate in severity its effectiveness is equivalent to that of morphine; for severe pain it is less effective than morphine.[10] These painkilling effects peak at about 3 hours, post-oral administration and last for approximately 6 hours.[11] These analgesic effects are only partially reversed by naloxone, hence indicating that its opioid action is unlikely the sole contributing factor; tramadol's analgesic effects are also partially reversed by α2 adrenergic receptor antagonists like yohimbine and the 5-HT3 receptor antagonist, ondansetron.[11] Pharmacologically, tramadol is similar to levorphanol and tapentadol in that it not only binds to the mu opioid receptor, but also inhibits the reuptake of serotonin and norepinephrine[2] due to its action on the noradrenergic and serotonergic systems, such as its "atypical" opioid activity.[14] Available dosage forms include capsules, tablets, including extended release formulations and injections.[10]
Pregnancy and lactation
Its use in pregnancy is generally advised against as it may cause some reversible withdrawal effects in the newborn.[15] A small prospective study in France found that, while there was an increased risk of miscarriages, there were no major malformations reported in the newborn.[15] Its use during lactation is also generally advised against, but a small trial found that infants breastfed by mothers taking tramadol were exposed to about 2.88% of the dose the mothers were taking. There was no evidence of this dose having a harmful effect on the newborn.[15]
Labour and delivery
Its use as an analgesic during labour is generally advised against due to its long-onset of action (one hour).[15] The ratio of the mean concentration of the drug in the fetus compared to that of the mother when it is given intramuscularly for labour pains has been estimated to be 94.[15]
Children
Its use in children is generally advised against, although it may be done under the supervision of a specialist.[10] On September 21, 2015 the FDA started investigating the safety of tramadol in use in persons under the age of 17. The investigation was initiated because some of these people have experienced slowed or difficult breathing.[16]
Elderly
There is an increased risk of opioid-related adverse effects such as respiratory depression, falls, cognitive impairment and sedation.[10]
Liver and kidney failure
It is advised that the drug be used with caution in those with liver or kidney failure, due to the high dependence of the drug on the liver and kidneys for metabolism to O-desmethyltramadol and elimination, respectively.[10]
Adverse effects
Main article: List of side effects of tramadol
Main side effects of tramadol. Red color denotes more serious effects, requiring immediate contact with health provider.[17]
The most common adverse effects of tramadol include nausea, dizziness, dry mouth, indigestion, abdominal pain, vertigo, vomiting, constipation, drowsiness and headache.[18][19] Compared to other opioids, respiratory depression and constipation are considered less of a problem with tramadol.[19]
There are suggestions that chronic opioid administration may induce a state of immune tolerance,[20] although tramadol, in contrast to typical opioids, may enhance immune function.[21][22][23] Some have also stressed the negative effects of opioids on cognitive functioning and personality.[24]
Interactions
Tramadol interacts with such serotonergics, monoamine oxidase inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, noradrenergic and specific serotonergic antidepressants, serotonin antagonist and reuptake inhibitors, certain analgesics (pethidine (meperidine), tapentadol, oxycodone, dextromethorphan and fentanyl), certain anxiolytics (such as the SSRIs and buspirone), certain antibiotics (namely, linezolid and isoniazid), certain herbs (e.g. St. John's wort, passiflora, etc.), amphetamines/substituted amphetamines, phenethylamines/Substituted phenethylamines, phentermine, lithium, methylene blue as well as numerous other therapeutic agents.[4][10] As it is a substrate of CYP3A4 and CYP2D6, any agents with the ability to inhibit or induce these enzymes will likely interact with tramadol. A pressor response similar to the so-called "cheese effect" was noted in combinations of amphetamine and tramadol, which appears to cause dysfunction of or toxicity to epinephrine/norepinephrine receptors.[10][19]
Contraindications
Its use is not advised for people deficient in CYP2D6 enzymes which accounts for about 6–10% of Caucasians and 1–2% of Asians, as they are crucial to the therapeutic effects of tramadol, by means of enabling tramadol's metabolism to O-desmethyltramadol.[10]
Overdose
Fatalities with tramadol overdose have been reported and are increasing in frequency in Northern Ireland; the majority of these overdoses involve other drugs including alcohol.[25] Recognised risk factors for tramadol overdose include depression, addiction and seizures.[25] Naloxone only partially reverses the toxic effects of tramadol overdose and may increase the risk of seizures.[10]
Physical dependence and withdrawal
Long-term use of high doses of tramadol will cause physical dependence and a withdrawal syndrome.[26] These include both withdrawal symptoms typical of opiate withdrawal and those associated with SSRI withdrawal, including numbness, tingling, paresthesia, and tinnitus.[27] Psychiatric symptoms may include hallucinations, paranoia, extreme anxiety, panic attacks, and confusion.[28] In most cases, tramadol withdrawal will set in 12–20 hours after the last dose, but this can vary.[27] Tramadol withdrawal lasts longer than that of other opioids; seven days or more of acute withdrawal symptoms can occur as opposed to typically three or four days for other codeine analogues.[27]
Psychological dependence and recreational use
Because of the possibility of convulsions at high doses for some users, recreational use can be very dangerous.[29] Tramadol can cause a higher incidence of nausea, dizziness, loss of appetite compared with opiates, which could deter recreational use.[30] Compared to hydrocodone, fewer persons choose to use tramadol recreationally.[31]
It may also have a large effect on sleeping patterns and high doses may cause insomnia, especially for those on methadone, both for maintenance and recreation. Though there is no scientific proof tramadol lessens effects of opiates or is a mixed agonist-antagonist, some people get the impression it is, while someone else might benefit being prescribed both for pain and breakthrough pain.[32]
Detection in biological fluids
Tramadol and O-desmethyltramadol may be quantified in blood, plasma or serum to monitor for abuse, confirm a diagnosis of poisoning or assist in the forensic investigation of a traffic or other criminal violation or a sudden death. Most commercial opiate immunoassay screening tests do not cross-react significantly with tramadol or its major metabolites, so chromatographic techniques must be used to detect and quantitate these substances. The concentration of O-desmethyltramadol in the blood or plasma of a person who has taken tramadol is generally 10–20% those of the parent drug.[33][34][35]
Chemistry
Synthesis and stereoisomerism
(1R,2R)-Tramadol (1S,2S)-Tramadol
(1R,2S)-Tramadol (1S,2R)-Tramadol
The chemical synthesis of tramadol is described in the literature.[36] Tramadol [2-(dimethylaminomethyl)-1-(3-methoxyphenyl)cyclohexanol] has two stereogenic centers at the cyclohexane ring. Thus, 2-(dimethylaminomethyl)-1-(3-methoxyphenyl)cyclohexanol may exist in four different configurational forms:
- (1R,2R)-isomer
- (1S,2S)-isomer
- (1R,2S)-isomer
- (1S,2R)-isomer
The synthetic pathway leads to the racemate (1:1 mixture) of (1R,2R)-isomer and the (1S,2S)-isomer as the main products. Minor amounts of the racemic mixture of the (1R,2S)-isomer and the (1S,2R)-isomer are formed as well. The isolation of the (1R,2R)-isomer and the (1S,2S)-isomer from the diastereomeric minor racemate [(1R,2S)-isomer and (1S,2R)-isomer] is realized by the recrystallization of the hydrochlorides. The drug tramadol is a racemate of the hydrochlorides of the (1R,2R)-(+)- and the (1S,2S)-(–)-enantiomers. The resolution of the racemate [(1R,2R)-(+)-isomer / (1S,2S)-(–)-isomer] was described[37] employing (R)-(–)- or (S)-(+)-mandelic acid. This process does not find industrial application, since tramadol is used as a racemate, despite known different physiological effects[38] of the (1R,2R)- and (1S,2S)-isomers, because the racemate showed higher analgesic activity than either enantiomer in animals[39] and in humans.[40]
Mechanism of action
Tramadol acts as a μ-opioid receptor agonist,[41][42] serotonin reuptake inhibitor and releasing agent,[43][44][45][46] norepinephrine reuptake inhibitor,[42] NMDA receptor antagonist (IC50=16.5 μM),[47] 5-HT2C receptor antagonist (EC50=26 nM),[48] (α7)5 nicotinic acetylcholine receptor antagonist,[49] TRPV1 receptor agonist,[50] and M1 and M3 muscarinic acetylcholine receptor antagonist.[51][52]
Tramadol has inhibitory actions on the 5-HT2C receptor. Antagonism of 5-HT2C could be partially responsible for tramadol's reducing effect on depressive and obsessive-compulsive symptoms in patients with pain and co-morbid neurological illnesses.[48] 5-HT2C blockade may also account for its lowering of the seizure threshold, as 5-HT2C knockout mice display significantly increased vulnerability to epileptic seizures, sometimes resulting in spontaneous death. However, the reduction of seizure threshold could be attributed to tramadol's putative inhibition of GABAA receptors at high doses.[47] In addition, tramadol's major active metabolite, O-desmethyltramadol, is a high-affinity ligand of the δ- and κ-opioid receptors, and activity at the former receptor could be involved in tramadol's ability to provoke seizures in some individuals, as δ-opioid receptor agonists are well known to induce seizures.[53]
Pharmacokinetics
O-desmethyltramadol
Tramadol undergoes hepatic metabolism via the cytochrome P450 isozyme CYP2B6, CYP2D6 and CYP3A4, being O- and N-demethylated to five different metabolites. Of these, O-desmethyltramadol is the most significant since it has 200 times the μ-affinity of (+)-tramadol, and furthermore has an elimination half-life of nine hours, compared with six hours for tramadol itself. As with codeine, in the 6% of the population that have reduced CYP2D6 activity (hence reducing metabolism), there is therefore a reduced analgesic effect. Those with decreased CYP2D6 activity require a dose increase of 30% in order to achieve the same degree of pain relief than those with a normal level of CYP2D6 activity.[54][55]
Phase II hepatic metabolism renders the metabolites water-soluble, which are excreted by the kidneys. Thus, reduced doses may be used in renal and hepatic impairment.[11]
Its volume of distribution is approximately 306 L after oral administration and 203 L after parenteral administration.[11]
Society and culture
Legal status
The U.S. Food and Drug Administration (FDA) approved tramadol in March 1995 and an extended-release (ER) formulation in September 2005.[56] It is covered by U.S. patents nos. 6,254,887[57] and 7,074,430.[58][59] The FDA lists the patents as scheduled for expiration on 10 May 2014.[58] However, in August 2009, U.S. District Court for the District of Delaware ruled the patents invalid, which, if it survives appeal, would permit manufacture and distribution of generic equivalents of Ultram ER in the United States.[60]
Effective August 18, 2014, Tramadol has been placed into Schedule IV of the federal Controlled Substances Act.[61][62] In addition, several states, including Arkansas, Georgia, Kentucky, Illinois, Mississippi, New York, North Dakota, Ohio, Oklahoma, South Carolina, Tennessee, West Virginia, Wyoming and the U.S. military have already classified Tramadol as a schedule IV controlled substance under state law.[63][64][65]
Thus, tramadol is classified as a Schedule IV in the US, Schedule 4 in Australia rather than as a Schedule 8 Controlled Drug like opioids.[10]
Sweden, as of May 2008, has chosen to classify tramadol as a controlled substance in the same way as codeine and dextropropoxyphene. This means that the substance is a scheduled drug. But unlike codeine and dextropropoxyphene, a normal prescription can be used at this time.[66]
The UK government has decided that tramadol will become a Schedule 3 controlled drug (CD) on 10 June 2014, but will have exemption from the safe custody requirement.[67]
Brand names
Grünenthal GmbH, which still owns the patent on tramadol, has cross-licensed the drug to pharmaceutical companies internationally. Thus, tramadol is marketed under many trade names around the world, including:
- Acugesic (Malaysia, Singapore)
- Adolonta (Spain)
- Algifeno (Bolivia)
- Algesia (Philippines)
- Anadol (Bangladesh, Thailand)
- Analgex (Chile)
- Analgex SAP (combined with paracetamol) (Chile)
- Astadol (combined with paracetamol)(Pakistan)
- Boldol (Bosnia, Herzegovina)
- Calmador (Argentina)
- Campex (Pakistan)
- Citra 50 (Mexico)
- Contramal (Belgium, France, India, Italy, Turkey, Sudan, Hungary)
- Conzip (United States)
- Crispin
- Cramol (Nepal)
- Cronus (combined with paracetamol) (Chile)
- Dolcet (combined with paracetamol)(Philippines)
- Dolol (Denmark)
- Doloten (combined with paracetamol) (Chile)
- Dolzam (Belgium, Luxembourg)
- Dromadol (United Kingdom)
- Durela (Canada)
- Exopen (South Korea)
- Ixprim (combined with paracetamol) (France, Ireland)
- Lumidol (Bosnia, Herzegovina, Croatia)
- Mabron (Bahrain, Bangladesh, Bulgaria, Czech Republic, Estonia, Iraq, Jordan, Latvia, Lithuania, Malaysia, Oman, Romania, Singapore, Sri Lanka, Sudan, Yemen)
- Mandolgin (Denmark)
- Mandolgine
- Manol Plus (combined with paracetamol) (Chile)
- Matrix (combined with paracetamol) (Honduras, Guatemala)
- Mavidol TR (combined with Ketorolac) (México)
- Minidol (Chile)
- Minidol Plus (combined with paracetamol) (Chile)
- Mosepan
- Nobligan (Argentina, Denmark, Iceland, Mexico, Norway, Portugal, Sweden)
- Nomal (Oman)
- Onetram (Japan)
- Osteodol (India)
- Oxxalgan PR (Greece)
- Palitex (India)
- Paratramol (combined with paracetamol) (Bulgaria (OTC))
- Pazital (combined with paracetamol) (Spain)
- Pengesic(Malaysia)
- Poltram (Poland)
- Pyredol (combined with paracetamol) (Vietnam, Bolivia)
- Ralivia (Canada)
- Relidol (Philippines)
- Ryzolt (United States)
- Sinergix (combined with ketorolac) (Mexico)
- Sintradon (Serbia, Russia)
- Siverol (Philippines)
- Tandol (South Korea)
- Timarol Par (combined with paracetamol) (Chile)
- Tiparol (Sweden)
- Tonoflex (Pakistan)
- Topalgic (France)
- Trabar (Cameroon)
- Tradol (Bangladesh, Ireland, Mexico, Singapore, Venezuela)
- Tradolan (Austria, Denmark, Finland, Iceland, Romania, Sweden)
- Tradolgesic (Thailand)
- Tradonal (Belgium, Indonesia, Italy, Luxembourg, Netherlands, Philippines, Spain, Switzerland)
- Tralgit (Czech Republic, Georgia, Romania, Slovakia)
- Tralodie (Italy)
- Tral P (combined with paracetamol) (Chile)
- Tramacet (combined with paracetamol) (Canada, Mexico, Costa Rica, South Africa)
- Tramacip (India)
- Tramadex (Israel)
- Tramadin (Finland)
- Trambulance
- Tramadol HEXAL (Denmark, Finland, Germany, Hungary)
- Traminol
- Trampel (Germany)
- Tram Proxyvon (INDIA)
- Tranophen (combined with paracetamol) (South Korea)
- Trexol (Mexico)
- TRIMIF (India)
- Trumen (Bangladesh)
- Tramabol
- Tramacet (South Africa)
- Tramadol (Australia, Belgium, Canada, Chile, Egypt, Estonia, France, Netherlands, Romania, New Zealand, Norway, Spain, United Kingdom, United States)
- Tramadol-Ratiopharm (Hungary, many European countries)
- Tramadolor (Austria, Estonia, Germany, Hungary, Latvia, Lithuania, Luxembourg, Romania)
- Tramadolor ID (Hungary)
- Tramalgic (Hungary, Czech Republic, Slovakia)
- Tramagit (Romania)
- Tramahexal (Australia)
- Tramake (United Kingdom)
- Trama-Klosidol (Argentina)
- Tramal (Slovakia, Costa Rica, Bulgaria, Colombia, Ecuador, Pakistan, Netherlands, Estonia, Finland, Croatia, Morocco, Slovenia, Austria, Poland, Brazil, Chile, Romania, Australia, Russia, New Zealand, Germany, Switzerland, Lebanon, Israel, Japan, Philippines, Egypt, Thailand, Portugal, Panama)
- Tramal Long (Chile)
- Tramalgic (Hungary)
- Tramal Gotas (Ecuador)
- Tramazac (India, Myanmar, Sri Lanka, South Africa)
- Tramazac Co (combined with paracetamol) (South Africa)
- Tramed
- Tramedo (Australia)
- Tramoda (Thailand)
- Trasic (Thailand)
- Tram Sham
- Tramól (Iceland)
- Tramundal (Austria)
- Tridol (South Korea)
- Tridural (Canada)
- Trodon (Serbia)
- Ultracet (combined with paracetamol) (Brazil, United States)
- Ultradol (Bangladesh)
- Ultram and Ultram ER (United States)
- Ultramed (combined with paracetamol) (India)
- Ultratram-P (combined with paracetamol) (India)
- Veldrol (Mexico)
- VAMADOL PLUS (India)
- Volcidol (Thailand)
- Zafin (combined with paracetamol) (Chile)
- Zaldiar (combined with paracetamol) (Australia, Belgium, Chile, Croatia, the Czech Republic, France, Israel, Mexico, Poland, Portugal, Slovenia, Spain, Switzerland, Russia, Panama)
- Zaledor XR
- Zaledor-P (combined with paracetamol) (Chile)
- Zamadol (United Kingdom)
- Zamudol (France)
- Zodol (Chile, Ecuador, Peru)
- Zoftadol (India)
- Zydol (United Kingdom, Ireland, Australia)
- Zytram (Canada, Iceland, New Zealand, Spain)
- Zytrim (Spain)
Veterinary medicine
Tramadol may be used to treat post-operative, injury-related, and chronic (e.g., cancer-related) pain in dogs and cats as well as rabbits, coatis, many small mammals including rats and flying squirrels, guinea pigs, ferrets, and raccoons.[68]
| Species | Half-life (h) for parent drug | Half-life (h) for O-desmethyltramadol | Maximum plasma concentration (ng/mL) for parent drug | Maximum plasma concentration (ng/mL) for O-desmethyltramadol |
|---|---|---|---|---|
| Camel | 3.2 (IM), 1.3 (IV) | – | 0.44 (IV) | – |
| Cat | 3.40 (oral), 2.23 (IV) | 4.82 (oral), 4.35 (IV) | 914 (oral), 1323 (IV) | 655 (oral), 366 (IV) |
| Dog | 1.71 (oral), 1.80 (IV), 2.24 (rectal) | 2.18 (oral), 90-5000 (IV) | 1402.75 (oral), | 449.13 (oral), 90–350 (IV) |
| Donkey | 4.2 (oral), 1.5 (IV) | – | 2817 (oral) | – |
| Goat | 2.67 (oral), 0.94 (IV) | – | 542.9 (oral) | – |
| Horses | 1.29–1.53 (IV), 10.1 (oral) | 4 (oral) | 637 (IV), 256 (oral) | 47 (oral) |
| Llama | 2.54 (IM), 2.12 (IV) | 7.73 (IM), 10.4 (IV) | 4036 (IV), 1360 (IM) | 158 (IV), 158 (IM) |
Pin cushion tree
In 2013, researchers reported that tramadol was found in relatively high concentrations (1%+) in the roots of the African pin cushion tree (Nauclea latifolia).[69] In 2014, however, it was reported that the presence of tramadol in the tree roots was the result of tramadol having been administered to cattle by farmers in the region:[70] tramadol and its metabolites were present in the animals' excreta, which contaminated the soil around the trees. Therefore, tramadol and its mammalian metabolites were found in tree roots in the far North of Cameroon, but not in the South where it is not administered to farm animals.[70]
A 2014 editorial in Lab Times online contested the notion that tramadol in tree roots was the result of anthropogenic contamination, stating that samples were taken from trees which grew in national parks, where livestock were forbidden; it also quoted researcher Michel de Waard, who stated that "thousands and thousands of tramadol-treated cattle sitting around a single tree and urinating there" would be required to produce the concentrations discovered.[71]
Research
Investigational uses
- Diabetic neuropathy [72][73]
- Antidepressant[74]
- postherpetic neuralgia [75][76]
- Premature ejaculation[77][78]
- Obsessive-compulsive disorder[79]
See also
- Indeloxazine
- Venlafaxine
References
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- ^ a b c d e f Brayfield, A, ed. (13 December 2013). "Tramadol Hydrochloride". Martindale: The Complete Drug Reference. Pharmaceutical Press. Retrieved 5 April 2014.
- ^ a b c "Ultram, Ultram ER (tramadol) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 28 November 2013.
- ^ a b "PRODUCT INFORMATION Tramadol SANDOZ 50 mg capsules" (PDF). TGA eBusiness Services. Sandoz Pty Ltd. 4 November 2011. Retrieved 6 April 2014.
- ^ Katz WA (1996). "Pharmacology and clinical experience with tramadol in osteoarthritis". Drugs. 52 Suppl 3: 39–47. doi:10.2165/00003495-199600523-00007. PMID 8911798.
- ^ Now What? DEA Tosses Tramadol in Schedule IV, By Nadia Awad, MedPage Today, Jul 10, 2014
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- ^ a b c d e Grond S, Sablotzki A (2004). "Clinical pharmacology of tramadol". Clinical Pharmacokinetics 43 (13): 879–923. doi:10.2165/00003088-200443130-00004. PMID 15509185.
- ^ Carville SF, Arendt-Nielsen S, Bliddal H, Blotman F, Branco JC, Buskila D, Da Silva JA, Danneskiold-Samsøe B, Dincer F, Henriksson C, Henriksson KG, Kosek E, Longley K, McCarthy GM, Perrot S, Puszczewicz M, Sarzi-Puttini P, Silman A, Späth M, Choy EH (2008). "EULAR evidence-based recommendations for the management of fibromyalgia syndrome". Annals of the Rheumatic Diseases 67 (4): 536–41. doi:10.1136/ard.2007.071522. PMID 17644548.
- ^ Lee CR, McTavish D, Sorkin EM (1993). "Tramadol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in acute and chronic pain states". Drugs 46 (2): 313–40. doi:10.2165/00003495-199346020-00008. PMID 7691519.
- ^ Micó JA, Ardid D, Berrocoso E, Eschalier A (2006). "Antidepressants and pain". Trends in Pharmacological Sciences 27 (7): 348–54. doi:10.1016/j.tips.2006.05.004. PMID 16762426.
- ^ a b c d e Bloor M, Paech MJ, Kaye R (2012). "Tramadol in pregnancy and lactation". International Journal of Obstetric Anesthesia 21 (2): 163–7. doi:10.1016/j.ijoa.2011.10.008. PMID 22317891.
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External links
- Medline Plus – Patient Information Medline Plus (A Service of the U.S. National Library of Medicine)
- U.S. National Library of Medicine: Drug Information Portal – Tramadol
- Tramadol in the treatment of RSD (RSD = Reflex Sympathetic Dystrophy)
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UpToDate Contents
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- 1. 変形性膝関節症のマネージメント management of knee osteoarthritis
- 2. 急性腰痛の治療 treatment of acute low back pain
- 3. 慢性腎臓病における慢性疼痛のマネージメント management of chronic pain in chronic kidney disease
- 4. オピオイド系薬剤を用いた癌疼痛のマネージメント：至適鎮痛作用 cancer pain management with opioids optimizing analgesia
- 5. 小児における疼痛の評価およびマネージメント evaluation and management of pain in children
English Journal
- Quantitation of the enantiomers of tramadol and its three main metabolites in human whole blood using LC-MS/MS.
- Haage P1, Kronstrand R2, Carlsson B3, Kugelberg FC2, Josefsson M4.
- Journal of pharmaceutical and biomedical analysis.J Pharm Biomed Anal.2016 Feb 5;119:1-9. doi: 10.1016/j.jpba.2015.11.012. Epub 2015 Nov 17.
- The analgesic drug tramadol and its metabolites are chiral compounds, with the (+)- and (-)-enantiomers showing different pharmacological and toxicological effects. This novel enantioselective method, based on LC-MS/MS in reversed phase mode, enabled measurement of the parent compound and its three
- PMID 26625281
- A novel composite matrix based on polymeric micelle and hydrogel as a drug carrier for the controlled release of dual drugs.
- Anirudhan TS1, Parvathy J2, Nair AS2.
- Carbohydrate polymers.Carbohydr Polym.2016 Jan 20;136:1118-27. doi: 10.1016/j.carbpol.2015.10.019. Epub 2015 Oct 12.
- In the present work, we present a system of hydrogel/micelle composite as dual-drug release vehicle. The hydrogel is prepared from poly(ethyleneglycol) PEG and poly(vinyl alcohol) PVA. Polymeric micelles are enjoying high resurgence of interest in biomedical field as promising candidates for the sta
- PMID 26572454
- Comment on: Pharmacokinetics of Tramadol and O-Desmethyltramadol Enantiomers Following Administration of Extended-Release Tablets to Elderly and Young Subjects.
- Allegaert K1,2.
- Drugs & aging.Drugs Aging.2016 Jan 8. [Epub ahead of print]
- PMID 26747059
Japanese Journal
- 経験と考察 肩腱板断裂および肩関節拘縮手術例に対するトラマドール塩酸塩/アセトアミノフェン配合錠の使用経験 : 肩の痛みに対する新たな選択肢
- 橋本 卓,原田 洋,諸岡 孝明 [他]
- 整形外科 = Orthopedic surgery 65(10), 1028-1033, 2014-09
- NAID 40020188303
- 経験と考察 人工膝関節全置換術後疼痛におけるトラマドール塩酸塩・アセトアミノフェン配合錠の使用経験
- 望月 猛,廣島 亮,高岡 宏光 [他]
- 整形外科 = Orthopedic surgery 65(4), 309-311, 2014-04
- NAID 40020027561
- 経験と考察 トラマドール塩酸塩・アセトアミノフェン配合錠投与初期の嘔気に対する制吐薬の効果 : 既存対照群との比較
- 阿部 泰之,猪川 輪哉,恒川 博巳 [他]
- 整形外科 = Orthopedic surgery 65(1), 21-25, 2014-01
- NAID 40019922097
Related Links
- UK Edition. Click here for US version. Tramadol hydrochloride 50mg capsules Tramadol Hydrochloride 50mg capsules Read all of this leaflet carefully before you start taking this medicine. Keep this leaflet. You may need ...
- Tramadol is a narcotic-like pain reliever used to treat moderate to severe pain. Fatal side effects can occur if you use this medicine with alcohol, or with other drugs that cause drowsiness or slow your breathing. Includes side effects ...
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★リンクテーブル★
| リンク元 | 「トラマドール」 |
| 関連記事 | 「hydrochloride」 |