Tramadol (marketed as the hydrochloride salt by Janssen Pharmaceutica as Ultram, and as generics) is used to treat moderate to moderately severe pain. عوارض 200 tramadol hydrochloride tablets It has two different mechanisms. عوارض 200 tramadol hydrochloride tablets First, it binds to the μ-opioid receptor. Second, it inhibits the reuptake of serotonin and norepinephrine.[4]
Tramadol is a centrally acting atypical opioid analgesic with additional serotonin-norepinephrine reuptake-inhibiting effects.[5] It is marketed as a racemic mixture of both R- and S-stereoisomers.[1] This is because the two isomers complement each other's analgesic activity.[1] It is often combined with paracetamol as this is known to improve the efficacy of tramadol in relieving pain.[1] Tramadol is an atypical opioid because it is a serotonin-norepinephrine reuptake inhibitor of and, by itself, a fairly weak μ-opioid receptor agonist.[6][7] Tramadol is metabolised to O-desmethyltramadol, which is a significantly more potent opioid with additional norepinephrine reuptake-inhibiting properties,[1] making it analogous to tapentadol.[8] When taken as an immediate-release oral formulation, the onset of pain relief usually occurs within about an hour.[9]
It was launched and marketed as Tramal by the German pharmaceutical company Grünenthal GmbH in 1977 in West Germany, even though it would take another 20 years for it to be launched in English-speaking countries such as the UK, U.S., and Australia.[5]
Despite the original belief that tramadol was a purely synthetic opioid it has been found in a South African tree.[
Medical uses[edit]
Generic tramadol HCl tablets marketed by Amneal Pharmaceuticals.
Tramadol HCl for injection
Tramadol is used primarily to treat moderate-severe pain, both acute and chronic.[11][12]
Tramadol is recommended for the management of pain in fibromyalgia by the European League Against Rheumatism.[13] 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.[11] 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.[14]
For pain moderate in severity its effectiveness is equivalent to that of morphine; for severe pain it is less effective than morphine.[11] These painkilling effects peak at about 3 hours, post-oral administration and last for approximately 6 hours.[12] 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.[12] 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[1] due to its action on the noradrenergic and serotonergic systems, such as its "atypical" opioid activity.[15] Available dosage forms include capsules, tablets, including extended release formulations and injections.[11]
Investigational uses[edit]
Diabetic neuropathy [16][17]
Antidepressant[18]
postherpetic neuralgia [19][20]
Acute opioid withdrawal management[21][22]
Obsessive-compulsive disorder[23]
Premature ejaculation[24][25]
Post-traumatic stress disorder[26]
Use in special populations[edit]
Pregnancy and lactation[edit]
Its use in pregnancy is generally advised against as it may cause some reversible withdrawal effects in the newborn.[27] Despite this 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.[27] 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 and despite this there was no evidence of this dose having a harmful effect on the newborn.[27]
Labour and delivery[edit]
Its use as an analgesic during labour is generally advised against due to its long-onset of action (one hour).[27] The ratio of the mean concentration of the drug in the foetus compared to that of the mother when it is given intramuscularly for labour pains has been estimated to be 94.[27]
Children[edit]
Its use in children is generally advised against, although it may be done under the supervision of a specialist.[11]
Elderly[edit]
There is an increased risk of opioid-related adverse effects such as respiratory depression, falls, cognitive impairment and sedation.[11]
Liver and kidney failure[edit]
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.[11]
Adverse effects[edit]
Main side effects of tramadol. Red color denotes more serious effects, requiring immediate contact with health provider.[28]
The most common adverse effects of tramadol include nausea, dizziness, dry mouth, indigestion, abdominal pain, vertigo, vomiting, constipation, drowsiness and headache.[29][30] Compared to other opioids respiratory depression and constipation is considered less of a problem with tramadol.[30]
By incidence[edit]
The most common side effects in order of decreasing incidence are:[2][3][31][32][33][34][35]
Note: عوارض 200 tramadol hydrochloride tablets Serious adverse effects are in bold.
Very common (>10% frequency) adverse effects include:
Dizziness
Nausea
Constipation
Vertigo
Headache
Vomiting
Somnolence
Common (1–10% frequency) adverse effects include:
Agitation
Anxiety
Emotional lability
Euphoria
Nervousness
Spasticity
Dyspepsia (indigestion)
Asthenia (weakness)
Pruritus (itchiness)
Dry mouth
Diarrhea
Fatigue
Sweating
Malaise
Vasodilation (dilation (widening) of blood vessels)
Confusion
Coordination disturbance
Miosis
Sleep disorder
Rash
Hypertonia
Abdominal pain
Weight loss
Visual disturbance
Flatulence
Menopausal symptoms
Urinary frequency
Urinary retention (being unable to urinate)
Uncommon (0.1-1% incidence) adverse effects include:
Cardiovascular regulation anomalies (palpitation, tachycardia, postural hypotension or cardiovascular collapse)
Retching
Gastrointestinal irritation (a feeling of pressure in the stomach, bloating)
Urticaria (hives)
Trembling
Flushing
Rare (0.01–0.1% incidence) adverse effects include:
Bradycardia
Hypertension (high blood pressure)
Allergic reactions (e.g. dyspnoea (shortness of breath), bronchospasm, wheezing, angioneurotic oedema)
Anaphylaxis
Changes in appetite
Paraesthesia (pins and needles)
Hallucinations
Tremor
Respiratory depression
Epileptiform convulsions
Involuntary muscle contractions
Abnormal coordination
Syncope (fainting)
Blurred vision
Dyspnoea (shortness of breath)
Tinnitus (ringing in the ears)
Migraine
Stevens-Johnson syndrome/Toxic epidermal necrolysis (potentially fatal skin reactions)
Motorial weakness
Creatinine increase
Elevated liver enzymes
Hepatitis (liver swelling)
Stomatitis (mouth swelling)
Liver failure
Pulmonary oedema (fluid in the lungs)
Gastrointestinal bleeding
Pulmonary embolism
Myocardial ischaemia (lack of blood supply to the heart muscles)
Speech disorders
Haemoglobin decrease
Proteinuria (protein in the urine; usually indicative of kidney damage)
There are suggestions that chronic opioid administration may induce a state of immune tolerance,[36] although tramadol, in contrast to typical opioids may enhance immune function.[37][38][39] Some have also stressed the negative effects of opioids on cognitive functioning and personality.[40]
Interactions[edit]
Tramadol interacts, potentially fatally, 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/subtituited amphetamines, phenethylamines/substituited phenethylamines, phentermine, lithium, methylene blue as well as numerous other therapeutic agents.[3][11] As it is a substrate of CYP3A4 and CYP2D6, hence any agents with the ability to inhibit or induce these enzymes will likely interact with tramadol. A pressor response similar to the cheese effect was noted in combinations of amphetamine and tramadol which appears to cause dysfunction of or toxicity to epinephrine/norepinephrine receptors.[11][30]
Contraindications[edit]
Its use is advised against in people lacking any 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.[11]
Overdosage[edit]
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.[41] Recognised risk factors for tramadol overdose include depression, male gender, addiction and seizures.[41] Naloxone only partially reverses the toxic effects of tramadol overdose and may increase the risk of seizures.[11]
Physical dependence and withdrawal[edit]
Long-term use of high doses of tramadol may be associated with physical dependence and a withdrawal syndrome.[42] The atypical withdrawal symptoms are probably related to tramadol's effect on serotonin and norepinephrine reuptake.[43] Symptoms may include those of SSRI discontinuation syndrome, such as anxiety, depression, anguish, severe mood swings, aggressiveness, brain "zaps", electric-shock-like sensations throughout the body, paresthesias, sweating, palpitations, restless legs syndrome, sneezing, insomnia, vivid dreams or nightmares, micropsia and/or macropsia, tremors, and headache among others.[43] In most cases, tramadol withdrawal will set in 12–20 hours after the last dose, but this can vary.[43] 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.[43] It is recommended that those physically dependent on pain killers take their medication regularly to prevent onset of withdrawal symptoms and this is particularly relevant to tramadol because of its SNRI properties and, when the time comes to discontinue their tramadol, they do so gradually over a period of time that will vary according to the individual, dose and length of time on the drug.[43][44][45][46][47]
Psychological dependence and recreational use[edit]
Because of the possibility of convulsions at high doses for some users, recreational use can be very dangerous.[48] Tramadol can cause a higher incidence of nausea, dizziness, loss of appetite compared with opiates, which could deter abuse.[49] Compared to hydrocodone, fewer persons choose to abuse tramadol.[50]
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.)[51]
Detection in biological fluids[edit]
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 concentrations of O-desmethyltramadol in the blood or plasma of a person who has taken tramadol are generally 10–20% those of the parent drug.[52][53][54]
Chemistry[edit]
Synthesis and stereoisomerism[edit]
(1R,2R)-Tramadol (1S,2S)-Tramadol
(1R,2R)-Tramadol (1S,2S)-Tramadol
(1R,2S)-Tramadol (1S,2R)-Tramadol
(1R,2S)-Tramadol (1S,2R)-Tramadol
The chemical synthesis of tramadol is described in the literature.[55] 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[56] 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[57] of the (1R,2R)- and (1S,2S)-isomers, because the racemate showed higher analgesic activity than either enantiomer in animals[58] and in humans.[59]
Mechanism of action[edit]
Tramadol acts as a μ-opioid receptor agonist,[60][61] serotonin releasing agent,[6][7][62][63] norepinephrine reuptake inhibitor,[61] NMDA receptor antagonist (IC50=16.5 μM),[64] 5-HT2C receptor antagonist (EC50=26 nM),[65] (α7)5 nicotinic acetylcholine receptor antagonist,[66] TRPV1 receptor agonist,[67] and M1 and M3 muscarinic acetylcholine receptor antagonist.[68][69]
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.[65] 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.[64] 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.[70]
Pharmacokinetics[edit]
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.[71][72]
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.[12]
Its volume of distribution is approximately, 306 L after oral administration and 203 L after parenteral administration.[12]
Society and culture[edit]
Legal status[edit]
The U.S. Food and Drug Administration (FDA) approved tramadol in March 1995 and an extended-release (ER) formulation in September 2005.[73] It is covered by U.S. patents nos. 6,254,887[74] and 7,074,430.[75][76] The FDA lists the patents as scheduled for expiration on 10 May 2014.[75] 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.[77]
Effective August 18, 2014, Tramadol has been placed into Schedule 4 of the federal Controlled Substances Act.[78][79] In addition, several states, including Arkansas, Georgia, Kentucky, Illinois, Mississippi, New York, North Dakota, Ohio, Oklahoma, Tennessee, West Virginia, Wyoming and the U.S. military have already classified Tramadol as a schedule IV controlled substance under state law.[80][81][82]
Thus, tramadol is classified as a Schedule 4 in the US, Schedule 4 in Australia rather than as a Schedule 8 Controlled Drug like opioids.[11]
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.[83]
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.[84]
Brand names[edit]
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)
Astadol (combined with paracetamol)(Pakistan)
Boldol (Bosnia, Herzegovina)
Calmador (Argentina)
Campex (Pakistan)
Citra 50 (Mexico)
Contramal (Belgium, France, India, Italy, Turkey, Sudan, Hungary)
Crispin
Cramol (Nepal)
Dolcet (combined with paracetamol)(Philippines)
Dolol (Denmark)
Dolzam (Belgium, Luxembourg)
Dromadol (United Kingdom)
Durela (Canada)
Exopen (South Korea)
Hovid (Malaysia)
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
Mosepan
Matrix (combined with paracetamol) (Honduras, Guatemala)
Mavidol TR (combined with Ketorolac) (México)
Nobligan (Argentina, Denmark, Iceland, Mexico, Norway, Portugal, Sweden)
Nomal (Oman)
Osteodol (India)
Oxxalgan PR (Greece)
Pazital (combined with paracetamol) (Spain)
Palitex (India)
Poltram (Poland)
Pyredol (combined with paracetamol) (Vietnam, Bolivia)
Ralivia (Canada)
Ryzolt (United States)
Sinergix (combined with ketorolac) (Mexico)
Sintradon (Serbia)
Siverol (Philippines)
Tandol (South Korea)
Tiparol (Sweden)
Tonoflex (Pakistan)
Topalgic (France)
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)
Tramacet (combined with paracetamol) (Canada, Mexico, Costa Rica, South Africa)
Tramacip (India)
Tramadex (Israel)
Tramadin (Finland)
Trambulance
Tramadol HEXAL (Denmark, Finland, Germany, Hungary)
Traminol
Tram Proxyvon (INDIA)
Tranophen (combined with paracetamol) (South Korea)
Trexol (Mexico)
TRIMIF (India)
Trumen (Bangladesh)
Tramabol
Tramadol (Australia, Belgium, Canada, Chile, Egypt, Estonia, France, Netherlands, Romania, New Zealand, Norway, Spain, United Kingdom, United States)
Tramadol Stada (Sweden)
Tramadol-Sandoz (Hungary)
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, New Zealand, Germany, Switzerland, Lebanon, Israel, Philippines, Egypt, Thailand, Portugal)
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)
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)
Veldrol (Mexico)
VAMADOL PLUS (India)
Volcidol (Thailand)
Zafin (combined with paracetamol) (Chile)
Zaldiar (combined with paracetamol) (Australia, Belgium, Chile, Croatia, the Czech Republic, France, Mexico, Poland, Portugal, Slovenia, Spain, Switzerland, Russia)
Zaledor (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[edit]
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.[85]
Pharmacokinetics of tramadol across the species[85]
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[edit]
In 2013, researchers discovered that tramadol is also produced naturally in relatively high concentrations (1%+) in the roots of the African pin cushion tree (Nauclea latifolia).[10]
See also[edit]
Bromadol
Ketobemidone
Venlafaxine
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ترامادول (نام ژنریک: Tramadol) کـه به نامـهای تجاری ترامال، عوارض 200 tramadol hydrochloride tablets ترامدو بایومادول نیز شناخته مـیشود. یک داروی مسکن شبه تریـاک هست و یک نوع اپیویید بـه حساب مـیآید. این دارو به منظور تسکین دردهای متوسط که تا شدید تجویز مـیشود. ترامادول یک آگونیست به منظور گیرندههای مو (μ) اوپیویید، و سیستم نورآدرنرژیروتونرژیک بوده و باعث افزایش آزاد سازی سروتونین مـیشود. خاصیت چسبندگی ترامادول بـه گیرندههای "مو" بسیـار ضعیف هست تقریباً ۶۰۰۰\۱ نسبت بـه مرفین، ماده متابولیزه شده O-Desmethyltramadol نسبت بـه عنصرمادر خاصیت چسبندگی بیشتری بـه گیرندههای "مو" دارد (۰،۱ برابر مرفین) و خاصیت مخدری قویتری از خود بـه جا مـیگذارد. خاصیت تسکین درد درون ترامادول حدود ۱۰ برابر ضعیف تر از مرفین است. علاوه بر این ترامادول باعث جلوگیری از بازجذب "نورآدرنالین" و افزایش آزاد سازی "سروتونین" مـیشود و غلظت این دو ماده را درون سیناپس بالا مـیبرد، این امر باعث ایجاد نوعی خاصیت، مانند داروهای ضسردگی و همچنین هوشیـاری مـیشود و برعمرفین فرد مصرف کننده را فعالتر مـیکند، حتی درون برخی از مصرفکنندگان حالات ضعیفی مانند (MDMA (XTC مشاهده شده، احتمال گرفتگی عضلانی نیز کاهش مـیابد. با خوردن ۱۰۰ مـیلی گرم ترامادول سطح خونی دارو درون دو ساعت بـه حداکثر مـیرسد. حدود ۲۰ درصد ترامادول بـه پروتئین خون بسته مـیشود. ۳۰ درصد ترامادول بصورت تغییر نیـافته و ۶۰ درصد آن بصورت متابولیتهای شکسته شده درون کبد از راه ادرار دفع مـیشود. نیمـه عمر دارو ۴ که تا ۶ ساعت مـیباشد. موارد مصرف ترامادول به منظور تسکین درد معمولاً بـه مدت کمتر از ۵ روز و به مقدار ۵۰ که تا ۱۰۰ مـیلی گرم هر ۸ ساعت تجویز مـیشود، همچنین این دارو جهت درمان سندروم پای بیقرار نیز تجویز مـیشود.[۲][۳][۴][۵]
تاریخچه[ویرایش]
این دارو توسط شرکت آلمانی گروننتال (Grünenthal) درون دهه ۱۹۷۰ با نام تجاری ترامال (®Tramal) ساخته شد. گروننتال درون سالهای بعد حق تولید ترامادول را بـه شرکتهای متعددی درون سراسر دنیـا واگذار کرد.
در سال ۲۰۱۳ پژوهشگران فرانسوی، سوئیسی و کامرونی درون پوسته ریشـه یک گیـاه دارویی افریقایی بـه نام N. latifolia ترامادول یـافتند. این کـه یک داروی مصنوعی درون مقادیر قابل توجهی درون طبیعت وجود داشته باشد یک پدیده بسیـار نادر است.[۶]
اشکال مختلف دارو[ویرایش]
ترامادول معمولاً بـه شکل نمک هیدروکلراید تولید شده و به دو شکل خوراکی (بیشتر کپسول و قرص) و آمپول بـه بازار عرضه مـیشود. مقدار جذب و تأثیر فرم تزریقی ترامادول بسیـار بیشتر از فرم خوراکی است. ترکیب ترامادول و استامـینوفن نیز درون بازار موجود هست (که درون ایران عرضه نمـیشود).[۷]
در خارج از ایران بـه صورت قرصهای آهسته رهش Retard، آمپول، کپسول و قطره موجود مـیباشد، مصرف قطره خوراکی آن رایجتر هست و برعاکثر داروهای اپیوئیدی شامل قوانین داروهای مخدر نمـیشود و با نسخه عادی پزشک قابل تهیـهاست.
اعتیـاد[ویرایش]
علائم جسمـی ترک ترامادول احتمالاً بـه علت خواص ضسردگی این دارو (جلوگیری از بازجذب سروتونین و نورآدرنالین) شدیدتر از علائم ترک مخدرهایی مانند تریـاک مـیباشد، حتی بعد از قطع مصرف کوتاه مدت ترامادول علائمـی مانند بی خوابی، سندروم پای بیقرار (RLS) و افسردگی بروز مـیکند. مصرف بدون وقفه آن درون طولانی مدت باعث ایجاد مقاومت بدنی نسبت بـه مواد اپیوییدی شده و دوز مصرف آن حتما افزایش یـابد که تا اثری مشابه مقدار مصرف اولیـه را ایجاد کند، مدتی بعد از قطع مصرف دارو مقاومت بدنی نسبت بـه ترامادول و دیگر مواد اپیوئیدی بـه حالت اولیـه بر مـیگردد.[۸]
با توجه بـه اینکه مکانیسم کنترل درد درون ترامادول مشابه مورفین است. مصرف مداوم آن منجر بـه وابستگی فیزیکی و روانی مشابه اعتیـاد بـه مواد مخدر مـیشود و مصرف طولانی مدت ترامادول منجر بـه اعتیـاد بـه آن شده و درمانی کاملا مشابه با درمان سوء مصرف مواد مخدری چون تریـاک، کراک و هروئین دارد.[۹]
عوارض جانبی[ویرایش]
عوارض مشابه دیگر داروهای شبهتریـاک (تهوع، سرگیجه، خواب آلودگی، خشکی دهان. دیر انزالی. یبوست، افت فشار خون، تعریق، خارش) درون ترامادول هم دیده مـیشود اما احتمال بروز دپرسیون تنفسی کـه کشندهترین عارضه این گروه داروهاست، با ترامادول خوراکی نسبت بـه مرفین کمتر است. مصرف این دارو بـه علت افزایش سطح سروتونین، بیشتر از دیگر مواد اپیوئیدی ایجاد حالت تهوع مـیکند، همچین باعث بی خوابی مـیشود. مصرف بیشتر از ۴۰۰ مـیلی گرم ترامادول به منظور افراد بدون مقاومت بدنی درون مقابل مواد اپیوئیدی خطرناک است.
مصرف همزمان داروهای مـهارکننده بازجذب سروتونین و مـهارکننده منوآمـینواکسیداز موجب تشدید عوارض دارو و گاهی سندرم سروتونین مـیگردند.
یکی از عوارض نادر ولی خطرناک مصرف ترامادول تشنج مـیباشد. تشنج معمولاً درون اثر مصرف زیـاد این دارو یـا مصرف دارو درون بیماران صرعی یـا بیمارانی کـه دچار آسیب مغزی شدهاند با بیمارانی کـه مشکلات کبدی کلیوی (دفع دارو دچار اختلال گشته و افزایش مقدار دارو درون خون) دارند و یـا معتادان بـه الکل ایجاد مـیگردد. همچنین احتمال وابستگی دارویی و بروز علائم ترک مشابه دیگر ترکیبات شبه تریـاک هم وجود دارد.[۱۰][۱۱] یکی دیگر از عوارض نادر ترامادول (چهار که تا پنج ساعت بعد از مصرف) افزایش فشار خون بـه همراه سردرد شدید مـیباشد مریم اخگری، رئیس بخش سمشناسی پزشکی قانونی تهران با اشاره بـه افزایش مصرف داروهای مخدر مانند متادون و ترامادول اعلام کرد درون مطالعهای کـه طی پنج سال اخیر انجام شده مرگهای ناشی از مصرف ترامادول ۴۰ برابر بیشتر شده است. درون این مقاله بـه نوع مرگ و تعداد قربانیـان اشاره نشده است.[۱۲]
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نویسنده و منبع | تاریخ انتشار: Wed, 19 Sep 2018 22:13:00 +0000