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Tramadol, the generic version of Ultram, is a centrally acting opioid analgesic. The exact mode of action of tramadol is unknown but it is said to work like morphine. Tramadol has dual mechanism of action. The results of clinical studies suggest that tramadol-induced antinociception is mediated by opioid (µ, mu) and non-opioid (inhibition of re-uptake of norepinephrine and serotonin) mechanisms. There is evidence that, in tramadol, both mechanisms act synergistically with respect to analgesia.

More specifically, tramadol enhances spinal pain inhibitory pathways by inhibiting neuronal re-uptake of serotonin (5-HT) and noradrenaline (NA), and stimulating 5-HT release. This added monoaminergic component possibly allows tramadol’s efficacy to stretch over a wider range of painful pathologies than other opioids.

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. Tramadol half-life is 6.3 h and 7.4 h of the metabolite. It may take from 31 to 38 hours to clear out of the system. The onset of analgesia begins approximately within one hour after administration.

Tramadol may be a useful alternative in patients with osteoarthritis who have not responded to first-line treatment with acetaminophen and in whom nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated, ineffective, or poorly tolerated. It appears to be relatively well tolerated for an opioid compound.

Tramadol appears to be an interesting therapeutic alternative for pain relief in postherpetic neuralgia, particularly in patients who are not depressed. Tramadol may be a choice for patients with obvious cardiovascular disease in whom antidepressants are contraindicated, and similarly in patients in whom an antidepressant effect is not required.

Compared with other treatments for Restless Leg Syndrome or RLS, tramadol seems to be superior in some cases, possibly because of its unique pharmacodynamic profile. In clinical study 12 patients with RLS (some of them treatment resistant or prone to side effects of previous medications) were treated with 50 to 150 mg of tramadol per day. The follow-up lasted from 15 to 24 months. 10 patients reported clear amelioration and 1 reported slight amelioration of their symptoms, while 1 reported no effect. Tramadol was described to be the most effective treatment and free of side effects when compared with several other treatments.

Tramadol is effective in patients with mild to moderately severe pain. It should be titrated to avoid nausea and dizziness associated with high initial doses. A tramadol/acetaminophen (Ultracet) (37.5/325 mg) combination has been shown to be effective for fibromyalgia pain without any serious adverse effects.

18 things you should know about tramadol.

1 - Tramadol is prescribed to treat moderate to moderately severe pain. Tramadol belongs to the class of drugs known as opiate agonists. Primarily, tramadol works by changing the way the body senses pain. Tramadol is not an NSAID (nonsteroidal anti-inflammatory drug).

2 - Tramadol is available in immediate release and extended release formulations. Tramadol may be prescribed as an immediate release tablet (50 mg.) or as Tramadol Extended Release tablet (100, 200, or 300 mg.). The extended release tablets are usually reserved for patients with chronic pain who require continuous, long-term treatment. Your doctor will determine the appropriate dosage schedule for you.

3 - Tramadol Extended Release tablets must be taken whole, not split, chewed or crushed. It is important to take tramadol properly and to follow prescribing instructions. If taken improperly or in a way that is not recommended, serious side effects and even death can result.

4 - Tramadol can be habit-forming for some people. Do not take more tramadol than has been prescribed for you. Taking more tramadol or taking it more often can cause dependency on it. You should also not stop taking tramadol without first consulting your doctor. You may experience withdrawal symptoms if you stopped it suddenly. You doctor will likely decrease your dose of tramadol gradually.

5 - Drug interactions are possible with tramadol. Carbamazepine (Tegretol^®, Tegretol XR^® , Equetro^®, Carbatrol^®) reduces the effect of tramadol by increasing its inactivation in the body. Quinidine (Quinaglute^®, Quinidex^®) reduces the inactivation of tramadol, thereby increasing the concentration of tramadol by 50%-60%. Combining tramadol with monoamine oxidase inhibitors (for example, Parnate^®) or selective serotonin inhibitors ((SSRIs, for example, fluoxetine, Prozac^®]) may result in severe side effects such as seizures or a condition called serotonin syndrome.

Tramadol may increase central nervous system and respiratory depression when combined with alcohol, anesthetics, narcotics, tranquilizers or sedative hypnotics. Be sure to tell your doctor about all medications you are taking.

6 - Tramadol is used to treat the following types of pain: dental pain, osteoarthritis pain, neuropathic pain, posttraumatic pain, postoperative pain, acute musculosketetal pain, labour pain, obstetrical analgesia, renal colic, diabetic neuropathy, postherpetic neuralgia, low back pain, chronic pancreatitis pain, rheumatoid arthritis pain.

7 - The use of tramadol during pregnancy should be avoided. Because the safety of tramadol use during pregnancy has not been established, the medication should not be used during pregnancy. The safe use of tramadol in nursing mothers has also not been established.

8 - 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.

The most common adverse events (incidence of 1.6% to 6.1%) were nausea, dizziness, drowsiness, sweating, vomiting and dry mouth. There have been patients who developed seizures after taking tramadol.

9 - A Cochrane Review of tramadol to treat osteoarthritis revealed some small benefit. The Cochrane Review stated that when tramadol is taken for up to 3 months, there may be decreased pain, improvements in function and stiffness and overall well-being. However, tramadol can cause side effects that are significant enough to require that the patient must stop taking the medication. Risks outweigh benefits for many people who have tried tramadol.

10 - Compared with NSAIDs, Nonsteroidal anti-inflammatory drugs, Tramadol does not aggravate hypertension or congestive heart failure, nor does it have the potential to cause peptic ulcers.

11 - Compared with opioid analgesics, Tramadol does not induce significant respiratory depression, constipation, or have significant abuse potential. The side effects of opioids include sedation, respiratory depression, constipation, and a strong sense of euphoria. In comparative study on postoperative pain after maxillofacial surgery, the potency ratio of tramadol to oxycodone was found to be approximately 8:1. There was no significant difference in the VAS, (Visual Analog Score), for pain. Tramadol was found to provide adequate analgesia after maxillofacial surgery without risk of respiratory depression.

13 - 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.

14 - Tramadol has a dose-dependent efficacy that lies between that of codeine and morphine, with a parenteral potency comparable to that of pethidine, or about 10-20% of that of morphine. Oral bioavailability is high (85-100%) and permits easy conversion from the oral to the parenteral route and visa versa.

15 - 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)

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

17 - Tramadol and morphine were compared for treatment of severe chronic pancreatitis pain and their interaction with gut motor function. Oral tramadol or morphine doses were titrated double-blinded and randomized for five days in 25 patients and pain, side effects, bowel function, orocecal and colonic transit, anal resting pressure, and rectal distension thresholds were measured. It is concluded tramadol and morphine are potent analgesics in severe chronic pancreatitis pain when individually titrated. Tramadol interfered significantly less with gastrointestinal function and was more often rated as an excellent analgesic than morphine.

18 - 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.

Advantages:

• generally well tolerated


• proven efficacy in a broad range of painful conditions


• respiratory depressionis less common and less pronounced than with other opioids


• lesser constipation effect than with other opioids


• withdrawal not considered to be as severe as that produced by other opioids


• low abuse and dependence potential


• more effective than NSAIDs for controlling post operative pain


• antidepressant-like (mood improving) activity


• local anesthetic activity


• low interaction potential


• devoid of immunosuppressive activity


• reasonably priced - available generic formulation

Disadvantages:

• risk of seizures


• risk of abuse, dependence and tolerance


• relatively high incidence of nausea and vomiting


• withdrawal symptoms following abrupt discontinuation


• short half-life necessitates dosing of immediate-release formulation every 4 to 6 hours

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