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Tramadol is a synthetic opioid narcotic pain killer used for treating moderate to severe pain. Tramadol's mechanisms are complex compared to most other opioids, because they include serotonin and norepinephrine reuptake inhibition in addition to μ-opioid receptor agonism. Tramadol's analgesic efficacy is about 10% of morphine's.
Tramadol (Ultram, Ultracet (also contains acetaminophen/paracetamol)) is a synthetic opioid narcotic pain killer used for treating moderate to severe pain. Tramadol's mechanisms are complex compared to most other opioids, because they include serotonin and norepinephrine reuptake inhibition in addition to μ-opioid receptor agonism; tramadol's analgesic effect is about 10% of that of morphine. 
Since it is an opioid narcotic, tramadol can be habit forming and can create dependance.  Many people who take only their prescribed dose, and for a short period, do not become dependant and often are able to stop taking tramadol without difficulty. Tramadol does appear to produce less dependence and constipation than equa-analgesic doses of strong opioids. However, because of its SNRI effects abrupt discontinuation of tramadol can caused the symptoms of SSRI discontinuation syndrome in many people. It is therefore recommended that tramadol be discontinued by tapering rather than all at once.
Injected tramadol solution has an analgesic potency about 10% of that of morphine. Tramadol's analgesic effects can be increased by combination with a non-opioid analgesic such as APAP (acetaminophen or paracetamol).
In adult patients with moderate to severe chronic pain not needing rapid relief, the recommended tramadol dosing is to start at 25 mg/day, adding another 25 mg dose every 3 days until 100 mg/day is reached. If needed the total daily dose can then be increased as tolerated by 50mg every 3 days to a maximum of 200 mg/day. A patient can then take 50—100mg for pain relief every 4 to 6 hours, but must not exceed 400mg/day.
For quick relief of acute pain, 50 mg to 100 mg of tramadol can be administered as needed every four to six hours, but must never exceed 400mg/day.
In no case should tramadol dosing exceed 400mg/day.
Use of tramadol is not recommended in patients under 18 years of age since the safety and efficacy in this population has not been established.
Tramadol should not be used during pregnancy; it has been shown to cross the placenta into the fetal blood system. Tramadol use during pregnancy has been associated with neonatal seizures, withdrawal syndrome, as well as fetal death and stillbirth.
Tramadol is not approved for use in treatment of addictive disorders. Although tramadol is an opioid agonist it does not adequately treat opioid or opiate withdrawal symptoms and should not be used in opioid-dependent patients. 
Tramadol can be administered orally by drops, capsules and sustained release tablets, by suppository rectally, and by intramuscular, intravenous and subcutaneous injection of tramamdol in solution.
Injection of crushed tramadol tablets is very dangerous. Injecting this form of tramadol whether IV, IM or subcutaneous risks overdose and death, and the fillers and binders in tramadol tablets when injected can cause local tissue necrosis, infection, pulmonary granulomas, and increased risk of endocarditis and valvular heart injury. Because of the weak opioid receptor agonist action of (+)-Tramadol, one must wait for its metabolism into (+)-Odesmethyl-tramadol (M1) in order to feel a opioid high, which with tramadol can happen only over a period of hours, so no rush will be experienced from tramadol injection, even the prepared solution which is intended for injection. See this thread for discussion of injecting tramadol: http://www.drugs-forum.com/forum/sho...light=tramadol
Tramadol is typically described as less euphoric than other opioids. Tramadol eases pain and causes very mild stimulation, having typical opioid effects and (rarely) visual and auditory hallucinations.
Dangerous combinations include tramadol with alcohol, hypnotics, narcotics, centrally acting analgesics, opioids or psychotropic drugs, since these may worsen central nervous system and respiratory depression through additive effects.
Tramadol reduces seizure threshold and thus the risk of seizure is increased if tramadol is taken in combination with: selective serotonin re-uptake inhibitors (SSRI antidepressants or anorectics), tricyclic antidepressants, and other tricyclic compounds (e.g., cyclobenzaprine, promethazine, etc.), other opioids, MAO inhibitors, Neuroleptics, or any other drugs that reduce the seizure threshold.
Combining tramadol with inhibitors of CYP2D6 such as fluoxetine, paroxetine, and amitriptyline could result in some inhibition of the metabolism of tramadol.
Combining tramadol with CYP3A4 inhibitors, such as ketoconazole and erythromycin, or inducers, such as rifampin and St. John’s Wort may affect tramadol's metabolism of tramadol.
A pilot study of the use of tramadol for treating obsessive compulsive disorder was published in 1997 and several cases of very quick remission of OCD symptoms have been reported in the literature, one of a patient with co-morbid Tourette's syndrome. The pilot study produced data showing tramadol may be a good alternative treatment for some patients with treatment-refractory OCD (patients who had not responded to standard treatments for the condition).
Tramadol is a synthetic centrally acting opioid analgesic racemate with two enantiomers, each having a different mode of analgesia activity. Tramadol is rapidly absorbed when taken orally and has a bioavailability of approximately 75%. Sustained-release tablets release tramadol over a period of 12 hours, reach peak concentrations after 4.9 hours and have a bioavailability of 87–95% compared with capsules. The mean elimination half-life of tramadol is about 6 hours. Tramadol and its metabolites are eliminated mainly through renal excretion. (+)-Tramadol and the metabolite (+)-Odesmethyl-tramadol (M1) are μ-opioid receptor agonists, (+)-Odesmethyl-tramadol 200 times more potent in μ-opioid binding than (+)-Tramadol. (+)-Tramadol inhibits serotonin reuptake and (–)-tramadol inhibits norepinephrine reuptake. Both SRI and NRI actions enhance inhibition of pain transmission in the spinal cord. Several animal models have shown that tramadol analgesia is only partially antagonized by naloxone. reference Metabolization of tramadol is by O- and N-demethylation and by conjugation reactions forming glucuronides and sulfates. The O-demethylation of tramadol is catalysed by cytochrome P450 (CYP) 2D6 and produces M1, the main analgesic effective metabolite. Tramadol N-demethylation to M2 is catalysed by CYP2B6 and CYP3A4. Because of CYP polymorphism in human populations, and tramadol having these two different metabolic pathways, the pharmacokinetics of tramadol are quite variable. As the parent molecule is metabolized, (+)-tramadol's SRI and (–)-tramadol NRI actions produce proportionally less of the analgesia effect, and the amount that M1's μ-opioid receptor agonism produces increases, so tramadol has a very complex pattern of pharmacological activity that is both metabolism and time-dependent. Because the main metabolic pathway of tramadol is via cytochrome P450 2D6 (CYP2D6), 5 to 15% of the white population metabolize tramadol poorly and do not get satisfactory analgesia from a standard dose.
LD50 (mg/kg) (as the hydrochloride)  :
Mice : 350 orally, 200 subcutaneously
Rat : 228 orally, 286 subcutaneously
Tramadol shares side-effects with other opioid analgesics. The most common side-effects of opioid analgesics include nausea and vomiting, constipation, dry mouth, and biliary spasm. Larger doses can produce muscle rigidity, hypotension, and respiratory depression. Other common side-effects include changes in heart rate such as tachycardia and bradycardia, palpitation, oedema, postural hypotension, hallucinations, vertigo, euphoria, dysphoria, mood changes, dependence, dizziness, confusion, drowsiness, sleep disturbances, headache, sexual dysfunction, difficulty with micturition, urinary retention, ureteric spasm, constriction of the pupils, visual disturbances, sweating, flushing, rash, and itchiness.
The most common side-effects specific to tramadol as an opioid analgesic include diarrhoea, retching, fatigue, paraesthesia (numbness, burning, or tingling). Stomach inflammation and flatulence are less common.
Rarely reported side-effects specific to tramadol include nightmares and hallucinations.
Seizures have been reported even in patients taking only recommended therapeutic doses of tramadol. Risk of seizure increases with doses above the recommended therapeutic range of 100-300mg/day, and is also increased when tramadol is combined with selective serotonin re-uptake inhibitors (SSRI antidepressants or anorectics), tricyclic antidepressants, other tricyclic compounds (e.g., cyclobenzaprine, promethazine, etc.), other opioids, MAO inhibitors, neuroleptics, or any other seizure threshold reducing drugs. Patients with epilesy, with a history of seizures, or with a recognized risk for seizure (from, for example, head trauma, metabolic disorders, alcohol and drug withdrawal, and/or CNS infections) are also at increased risk of seizure if taking tramadol. Administering naloxone to someone on tramadol also increases seizure risk.
Tramadol has been reported as involved in cases of serotonin syndrome when taken with serotonergic drugs such as fluoxitine, sertraline, paroxitine, citralopam, fluvoxamine, venlafaxine, mirtazapine and tricyclic antidepressants. Serotonin syndrome symptoms may include hallucinations, agitation and coma, tachicardia (heart rate over 100 beats per minute), fluctuating blood pressure, and hyperthermia, as well as hyperreflexia, poor coordination, nausea, vomiting, and diarrhea.
Suddenly stopping tramadol rather than tapering can cause withdrawal symotoms including anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection, and rarely, hallucinations. More rarely withdrawal can cause panic attacks, severe anxiety, and paresthesias. Tapering off tramadol can reduce the ocurrance of withdrawal symptoms.
For experiences of withdrawal see this DF thread: http://www.drugs-forum.com/forum/sho...d.php?t=181177
Tramadol overdose can cause respiratory depression, sleepiness, unconsciousness or coma, skeletal muscle flaccidity, cold, clammy skin, constricted pupils, seizures, very low heart rate, low blood pressure, heart attack, and death.
Naloxone reverses some symptoms caused by tramadol overdose, however it also increases risk of seizure. Studies have shown that naloxone does not change the lethality of an tramadol overdose in mice. Barbiturates and benzodiazepines can suppress seizures caused by tramadol overdose. Hemodialysis is unlikely to help treat tramadol overdose because it removes at most 7% of the dose in a 4 hour period.
Cases of death due to tramadol overdose have been reported, some in combinations with other substances such as alcohol and benozodiazepines, the fatalities having tramadol blood concentrations from 2mg/L - 38 mg/L (therapeutic levels are 0.1-0.3mg/L). The death due to tramadol with only a 2mg/L blood concentration was a 6 month old child. 
Tramadol can impair mental abilities necessary for safe performance of things such such as driving a car or operating machinery.
Blood disorders have also been reported.
Typical opiod side effects have been reported including dizziness, somnolence, nausea, constipation, sweating and pruritus. Serious anaphylactic reactions have been reported in patients, sometimes but rarely fatal, and often following the first dose. Additional reported allergic reactions include pruritus, hives, bronchospasm, angioedema, toxic epidermal necrolysis and Stevens-Johnson syndrome.
Tramadol use has been shown to cause craving, drug-seeking behaviour and the development of tolerance. Tramadol dependence has been reported, and tramadol can re-initiate physical dependence in patients previously dependent or chronically using other opioids.
Merck Index, fifteenth edition (2013)
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