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Tramadol
Trakem

  • Ultram / Rybix / Tramal / UDT
  • PAR009
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Tramadol, with the chemical formula cis-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)-cyclohexanol hydrochloride, is a 4-phenylpiperidine analog of codeine. It is a usual go-to medication as it has less potential for abuse and respiratory depression. Tramadol can be found as 2 enantiomers with active analgesic properties however, the mechanism of action of each of the enantiomers differs greatly. In the FDA records, the first approved tramadol product was developed by Actavis Elizabeth and FDA approved in 2002.

Tramadol is approved for the management of moderate to severe pain in adults.

As an off-label indication, tramadol has been investigated to be used for the treatment of premature ejaculation.

Tramadol inhibits the descending pain pathways at the spinal level. There are reports supporting the fact that tramadol activity goes beyond the inhibition of opioid receptors. In this reports the administration of Naloxone only reduced the activity of tramadol by 30%. Those reports also indicate that the inhibition of metabolic enzymes, used for the generation of M1 which has a very high affinity for opioids, does not affect tramadol-induced analgesia.

The inhibition of neurotransmitters by both tramadol enantiomers has been shown to enhance the inhibitory descending pathways associated with pain transmission in the CNS. At the same time, it presents local anesthetic properties by blocking potassium channels and its secondary mechanisms of action are thought to increase the activity of endogenous inhibitory control and decrease pain transmission which would explain the central analgesic effects of tramadol.

From the racemic form, the (+)-tramadol seems to be more effective but less tolerated if administered alone. This indicates the importance of having the racemic mix in order to have the most optimal results. The effect of this racemic mix is compared to be of about 20% of the effect of morphine.

Tramadol has a dual action of pain relief by acting as both a central opiate agonist and a central nervous system reuptake inhibitor of norepinephrine and serotonin. (+)-Tramadol and its O-desmethyl metabolite (M1) are selective and weak mu receptor agonist which in order, alter the release of nociceptive neurotransmitters.

From these two molecules, the metabolite M1 metabolite has 300 times more affinity for this receptor while (+)-tramadol also inhibits serotonin reuptake. On the other hand, (-)-tramadol inhibits norepinephrine reuptake.

Other than this major mechanism of action, tramadol is known and fully studied due to its inhibitory activity against alpha2-adrenoreceptors, neurokinin 1 receptors, and muscarinic receptors as well as the inhibition of ion channels via nicotinic acetylcholine receptor and N-methyl-D-aspartate receptor.

Metabolism: Tramadol undergoes extensive first-pass metabolism in the liver by N- and O- demethylation and conjugation. From the extensive metabolism, there have been identified at least 23 metabolites.

Absorption: Oral administration of a dose of 100 mg of racemic tramadol has been shown to present a very rapid absorption and distribution. The reported peak concentration of 0.31 mg/L is reached after only 2 hours of the administration. The bioavailability of tramadol has ranged from 75 to 90% depending on the tested individual and this bioavailability does not change according to any diet.

Route of elimination: Tramadol is eliminated primarily through metabolism by the liver and the metabolites are excreted primarily by the kidneys, accounting for 90% of the excretion while the remaining 10% is excreted through feces. Approximately 30% of the dose is excreted in the urine as unchanged drug, whereas 60% of the dose is excreted as metabolites.

Half life: Tramadol reported a half-life of 5-6 hours while the M1 metabolite presents a half-life of 8 hours.

All medicines may cause side effects, but many people have no, or minor, side effects.Some medical conditions may interact with Tramadol.

Tell your doctor or pharmacist if you have any medical conditions.

Common tramadol side effects may include: headache, dizziness, drowsiness, tired feeling, constipation, diarrhea, nausea, vomiting, stomach pain, feeling nervous or anxious, itching, sweating, flushing, warmth, redness, or tingly feeling, dry mouth.

Overdose can be observed as a coma or stupor driven from somnolence, constricted pupils, seizures, respiratory depression, bradycardia, hypotension, cardiac arrest, and death. In case of overdose, re-establish patient airway and institute assisted or controlled ventilation. In presence of cardiac arrest or arrhythmias, it might be needed the use of cardiac massage or defibrillation.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider.

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