eMedExpert Home > Compare Drugs > Tramadol

• Tramadol hydrochloride
• Mechanism of action
• Side effects
• Tramadol vs. Codeine
• Tramadol vs. Meperidine
• Tramadol vs. Morphine
• Tramadol vs. Codeine combinations
• Comparison with NSAIDs
• Drug abuse and dependence

Tramadol hydrochloride is an orally active, centrally acting analgesic with a dual mechanism of action introduced in July 1994. It has been used in post-surgical pain, obstetric pain, and chronic pain of mechanical and neurogenic origin. Analgesic tolerance is not a significant problem, and psychological dependence and euphoric effects are minimal.

There are a significant number of patients in the chronic group who develop side-effects, but many of those who tolerate the drug get useful benefit in pain reduction. The most common adverse events (incidence of 1.6 to 6.1%) were nausea, dizziness, drowsiness, sweating, vomiting and dry mouth.

Unlike other opioids, tramadol has no clinically relevant effects on respiratory or cardiovascular parameters. Tramadol may prove particularly useful in patients with poor cardiopulmonary function, including the elderly, the obese and smokers, in patients with impaired hepatic or renal function, and in patients in whom nonsteroidal anti-inflammatory drugs are not recommended or need to be used with caution.

Several different studies on tramadol have shown the following:

• Tramadol has a dose-dependent efficacy that lies between that of codeine and morphine, with a parenteral potency comparable to that of pethidine, i.e. about 10-20% of the gold standard morphine. Oral bioavailability is high (85-100%) and permits easy conversion from the oral to the parenteral route and visa versa.
• Tramadol has been demonstrated to provide superior analgesia to combined acetaminophen-propoxyphene (i.e. Darvocet) in patients experiencing severe postoperative pain, and similar analgesia.
• Four-week study of 390 elderly patients with chronic pain secondary to a variety of conditions, tramadol was found to provide comparable analgesia to acetaminophen with codeine without a significant difference in associated adverse effects.
• A meta-analysis of RCTs in patients with acute pain found that single doses of tramadol 75mg to 150mg had analgesic efficacy similar to combinations of paracetamol 650mg plus propoxyphene 100mg and aspirin 650mg plus codeine 60mg. Short-term studies in chronic pain have shown tramadol 100mg three times a day to be as effective as dextropropoxyphene 100mg three times a day, and tramadol 50mg to be as effective as paracetamol 300mg plus codeine 30mg (both up to 8 capsules a day)

Tramadol shows a selective interaction with mu receptors, which are responsible for nociception, and has weak pharmacodynamic activity on other opioid receptors. At the same time, it acts synergistically on neuroamine transmission by inhibiting synaptic noradrenaline (norepinephrine) reuptake and inducing intrasynaptic serotonin (5-hydroxytryptamine; 5-HT) release.

Respiratory depression with tramadol is less pronounced, and occurs less often, in comparison to equianalgesic doses of morphine. In large clinical and post-marketing studies including over 21,000 patients, no clinically relevant respiratory depression was reported. However, respiratory depression can occur, in particular with overdose or with impaired renal function.

Another opioid side effect, which is reduced with tramadol use, is constipation. Clinically this has proven to be a significant advantage with long-term therapy, but could also be beneficial in the prevention of ileus postoperatively.

Sweating is a side effect specific to tramadol, due to its monoaminergic effects.

Tramadol appears to carry the same risk of urinary disorders (difficulty in micturition, urinary retention) as other opiates.

Relative to codeine, tramadol has similar analgesic properties but may have fewer constipating, euphoric, and respiratory depressant effects.

Metanalysis by Moore and McQuay indicates an appropriate dose response curve for tramadol, and suggests a reduced number needed to treat to show therapeutic efficacy as compared with codeine, in doses of 75 to 150 mg. Nausea, vomiting and dizziness are greater than with codeine, somnolence about the same and constipation much less. In the chronic pain situation nausea and vomiting are attenuated with usage, as is somnolence for both drugs, but constipation remains a particular problem with codeine and dihydrocodeine, and less of a problem with tramadol.

In the study was evaluated the efficacy and side effects of tramadol comparing with meperidine in the treatment of shivering during spinal anesthesia in cesarean section. Tramadol has advantages over meperidine in that it is not a controlled drug and it causes less respiratory depression and dizziness than other opioids at equivalent dosages

Tramadol is more effective in controlling post-spinal shivering but results in more frequent nausea, vomiting and somnolence in comparison with meperidine.

• Efficacy of tramadol versus meperidine for pain relief and safe recovery after adenotonsillectomy

Tramadol administration may produce a set of symptoms (including dizziness, somnolence, nausea, constipation, sweating and pruritus) similar to that of an opioid. However, tramadol causes significantly less respiratory depression than morphine. 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 changes in blood pressure have been observed.

Different studies have shown:

• Tramadol may represent a superior choice over morphine for children undergoing adenotonsillectomy, with a potential to cause less postoperative sedation and respiratory depression.
• Tramadol is as effective as morphine for moderate postoperative pain but it does appear to be less effective for severe acute pain.
• Tramadol has been compared with morphine in patients with post-traumatic musculoskeletal pain in the pre-hospital setting. Intravenous tramadol 100mg was equivalent to 5-10mg morphine, with similar incidence of side effects and similar degree of patient satisfaction
• A comparison of the postoperative analgesic efficacy of single-dose epidural tramadol versus morphine in children
• Effect of tramadol and morphine on pain

Tramadol maximum analgesic efficacy for relieving acute pain after oral surgery appears to be similar to that of 60 milligrams of codeine alone but less than that of a full therapeutic dose of a nonsteroidal anti-inflammatory drug or a codeine combination, such as aspirin/codeine or acetaminophen/codeine.

Tramadol has limited indication for management of acute pain in dentistry, possibly as an alternative analgesic when gastrointestinal side effects contraindicate the use of nonsteroidal anti-inflammatory drugs and when codeine/acetaminophen combination analgesics are not well-tolerated or are contraindicated.

• Pain management in dental practice: Tramadol vs. codeine combinations - The Journal of the American Dental Association

Oral tramadol can deliver the same analgesic efficacy as oral diclofenac for posttonsillectomy pain relief, which might be beneficial for avoiding the adverse effects of nonsteroidal anti-inflammatory drug therapy.

• Tramadol vs Diclofenac for Posttonsillectomy Analgesia

In comparative studies of tramadol and ketorolac in nasal surgery and orthopaedic surgery, improvements in postoperative analgesia and quality of sleep were similar with intramuscular tramadol or ketorolac.

Comparative study showed that tramadol is a better analgesic compared to ketorolac for patients undergoing day care gynaecological laparoscopic procedure. This study suggests that analgesic efficacy of ketorolac is not adequate for diagnostic laparoscopic procedures. Tramadol on the other hand provided better analgesia and was well tolerated, but incidence of postoperative nausea and vomiting was higher with tramadol and recovery time was prolonged. However, with ketorolac group the incidence of nausea and vomiting were lower and recovery time shorter, but there was a high requirements of opioid analgesia in the postoperative period.

Unlike other opioids, tramadol is not usually associated with the development of tolerance, physical dependence or psychological addiction.

Although tramadol can produce drug dependence of the mu-opioid type (like codeine or dextropropoxyphene) and potentially may be abused, there has been little evidence of abuse in foreign clinical experience. In clinical trials, tramadol produced effects similar to an opioid, and at supratherapeutic doses was recognized as an opioid in subjective/behavioral studies. Tolerance development has been reported to be relatively mild and withdrawal when present, is not considered to be as severe as that produced by other opioids. Part of tramadol's activity and some extension of the duration of mu-opioid activity. Delayed mu-opioid activity is believed to reduce a drug's abuse liability.

• 1. The Merck Manual of Medical Information. Mark H. Beers et al., eds. 2nd Home Edition. Whitehouse Station, NJ: Merck; 2003.

Published: May 05, 2007
Last updated: January 07, 2010