Drug Index


Ultram, Ultram ER (slow release), Ultracet (tramadol combined with acetaminophen)

none known

Tramadol is a centrally acting synthetic opioid analgesic (pain killer). Although its mode of action is not completely understood, from animal tests, at least two complementary mechanisms appear applicable: binding of parent and M1 metabolite to µ-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin. Opioid activity is due to both low affinity binding of the parent compound (tramadol) and higher affinity binding of the O-demethylated metabolite (called M1) to µ-opioid receptors. The analgesic activity of tramadol is due to both parent drug and the M1 metabolite. In animal models, M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in mu (µ)-opioid receptor binding. The relative contribution of both tramadol and M1 to human analgesia is dependent upon the plasma concentrations of each compound. Tramadol has been shown to inhibit reuptake of norepinephrine and serotonin, as have some other opioid analgesics. These mechanisms may contribute independently to the overall analgesic profile of tramadol. Analgesia in humans begins approximately within one hour after administration and reaches a peak in approximately two to three hours. Tramadol and its metabolites are excreted primarily in the urine with observed plasma half-lives of 6.3 and 7.4 hours for tramadol and M1 respectively. Tramadol is extensively metabolized after oral administration. It is eliminated primarily through metabolism by the liver [ "N " (mediated by CYP3A4 and CYP2B6) and "O" (mediated by CYP2D6) demethylation and glucuronidation or sulfation]. One metabolite (O-desmethyl tramadol -- called M1) and the metabolites are eliminated primarily by the kidneys. Approximately 30% of the dose is excreted in the urine as unchanged drug, whereas 60% of the dose is excreted as metabolites.

Tramadol is indicated for the management of moderate to moderately severe pain.


When Ultram (tramadol) was first introduced in the United States, doctors were told that it had almost no addictive potential. Time has proven that statement to be false. Unfortunately, a lot of physicians still remember how the drug touted as having very low addictive potential and they believe that they are avoiding problems with opiate dependence by prescribing tramadol, in lieu of other opiates such as hydrocodone. The fact is that tramadol is an opioid agonist of the morphine-type. Such drugs are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. A symptom that is easily detected with opiate use is pinpoint pupils (miosis). Psychological dependence may occur early in use of this medication, but physical dependence and tolerance may develop upon repeated administration (requiring larger or more frequent dosages of tramadol to produce relief of pain or achieve a state of euphoria). . When tramadol is abused, the individual is seeking the euphoric effect ("high"). Usually, doses higher than the recommended dosage are used to reach a state of euphoria. Tramadol could also be abused by crushing, chewing, snorting, or injecting the dissolved product, thus predisposing to overdose or death. Mild signs of withdrawal can occur in some individuals after using tramadol for several days consecutively. Addiction to this drug can occur, even if taken as prescribed, when used for several weeks consecutively. When taken for treatment of chronic pain for several weeks or months consecutively, tolerance and dependence often occur. Once an individual has become dependent on tramadol, a primary driving force to continue using it (or substituting other opiate agonists) is to prevent the very unpleasant neurochemical and physical withdrawal syndrome associated with discontinuing this drug. Symptoms usually associated with withdrawal may include:

  • • Abdominal pain
  • • Muscle aches
  • • Joint pain
  • • Sleep problems (insomnia)
  • • Agitation
  • • Restlessness
  • • Diarrhea
  • • Dilated pupils
  • • Goose bumps
  • • Nausea
  • • Runny nose
  • • Sweating
  • • Vomiting
  • • Restlessness
  • • Yawning
  • • Loss of appetite (anorexia)
  • • Rapid heart rate
  • • Elevated blood pressure
  • • Rapid breathing
  • • Eyes or nose watering

(Note: the term "going cold turkey" comes from the gooseflesh that occurs during withdrawal that looks like the skin of a plucked turkey) Withdrawal of tramadol is best handled by a physician that is skilled at assisting patients with opiate detoxification. Medications may be necessary to help control symptoms of withdrawal.

Acute overdosage with tramadol can be manifested by respiratory depression, somnolence( extreme sleepiness) progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, bradycardia (abnormally slow heart rate), hypotension (abnormally low blood pressure), and death. Deaths due to overdose have been reported with abuse and misuse of tramadol by ingesting, inhaling, or injecting the crushed tablets. Review of case reports has indicated that the risk of fatal overdose is further increased when tramadol is abused concurrently with alcohol or other CNS depressants, including other opioids. Fatalities have been reported in post marketing in association with both intentional and unintentional overdose with tramadol. While naloxone will reverse some, but not all, symptoms caused by overdosage with tramadol, the risk of seizures is also increased with naloxone administration. Hemodialysis is not expected to be helpful in an overdose because it removes less than 7% of the administered dose in a 4 hour dialysis period.

Any patient with a history of alcohol or substance dependence has a higher than average risk for developing addiction to tramadol. If use of this medication is considered necessary for the management of pain, the lowest dose of this medication that is sufficient to provide pain relief is warranted. It is also recommended that use of this medication in an addict be discontinued as soon as possible and pain management thereafter managed with non-addictive medications. Respiratory depression can occur with all opioid agonist medications. Caution should be exercised when prescribing this medication to individuals with impaired lung function or low blood pressure. There may be serious problems also with use of this medication an individual with a closed head injury. It can elevate cerebrospinal fluid pressure and mask symptoms of closed head injury that could require immediate medical measures. The administration of tramadol, like all opioid analgesics, may obscure the diagnosis or clinical course in patients with acute abdominal conditions. Individuals with kidney (renal) or liver (hepatic) impairment must be monitored closely because the concentration of tramadol and its metabolites in the bloodstream can be higher than in subjects with normal kidney or liver function. Seizures have been reported in patients receiving tramadol within the recommended dosage range. Spontaneous post-marketing reports indicate that seizure risk is increased with doses of tramadol above the recommended range. Concomitant use of tramadol increases the seizure risk in patients taking: Selective serotonin re-uptake inhibitors (SSRI antidepressants or anorectics), tricyclic antidepressants (TCAs), and other tricyclic compounds (e.g., cyclobenzaprine, promethazine, etc.), MAO inhibitors, neuroleptics, other opiates, or other drugs that reduce the seizure threshold. Because of its added depressant effects, tramadol should be prescribed with caution for those patients whose medical condition requires the concomitant administration of sedatives, tranquilizers, muscle relaxants, antidepressants, or other CNS-depressant drugs. It is extremely important to tell your doctor or pharmacist about every drug you are taking (including “street” drugs) and your alcohol consumption before using tramadol. Risk of convulsions may also increase in patients with epilepsy, those with a history of seizures, or in patients with a recognized risk for seizure (such as head trauma, metabolic disorders, alcohol and drug withdrawal, central nervous system infections). The development of a potentially life-threatening serotonin syndrome may occur with the use of tramadol products, particularly with concomitant use of serotonergic drugs such as SSRIs, SNRIs, TCAs, MAOIs and triptans, with drugs which impair metabolism of serotonin (including MAOIs), and with drugs which impair metabolism of tramadol (CYP2D6 and CYP3A4 inhibitors). This may occur within the recommended dose. It can also be dangerous if tramadol is used with other sedative/hypnotic drugs, other opiates (narcotics), muscle relaxers, sedating "street drugs", or alcohol. The combination of these drugs with tramadol can cause a multiplied effect of the potency of each drug.

Apart from analgesia, tramadol administration may produce a constellation of symptoms (including dizziness, somnolence, nausea, constipation, sweating and pruritus) similar to that of other opioids. In contrast to morphine, tramadol has not been shown to cause histamine release. At therapeutic doses, tramadol has no effect on heart rate, left-ventricular function or cardiac index. Orthostatic hypotension has been observed. Adverse effects may include allergic reaction, confusion, temporary hallucination, dry mouth, nervousness, tremor, rash, blurred vision, mental clouding, lethargy, mood changes, urinary retention, anxiety, fear, respiratory depression, and personality changes.


*This is a condensed description of tramadol. For more details check with your physician, pharmacist, or resources such as The Physicians' Desk Reference (PDR),




Our Partners in Recovery