Tramadol

What is Tramadol? ¹

• Synthetic opioid with analgesic properties indicated for treatment of moderate-severe pain.
• Can be administered orally as immediate release or extended release tablets or as a liquid formulation.

Mechanism of Action & Pharmacokinetics ¹²

• Atypical synthetic opioid with synergistic opioid and non-opioid effects. Activates both the μ-opioid and monoamine receptor systems:
  • Opioid: Selectively binds to opiate receptors in the central nervous system. Tramadol is broken down to active metabolite M1 by liver enzyme CYP2D6. M1 is a more potent analgesic with stronger affinity for opiate receptors.
  • Non-opioid/SNRI + SSRI: The two enantiomers of tramadol each independently inhibit norepinephrine and serotonin reuptake, which activate the inhibitory descending pathway - producing an antinociceptive effect with alteration of pain perception.
• Tramadol and its M1 metabolite reach maximum plasma concentration in 2 and 3 hours with a half-life of and 6 and 8 hours, respectively.
• Metabolized by liver enzymes through conjugation and metabolites are primarily renally excreted.

Dosage ¹³

• Extended release: 100, 200, or 300 mg tablet once daily.
• Immediate release: 50 mg tablet or 5 mg/ml solution.
  • Acute pain: 50-100 mg every 4-6 hours with a daily maximum of 400 mg/d.

Indications ¹²

• Moderate to severe pain. Commonly used postoperatively.
• Extended release: pain lasting longer than a week.
• Immediate release: pain lasting less than a week, and not to be used "as needed" but rather with scheduling dosing.

Adverse effects ^{12 3}

• As with other opiates, risk for development of tolerance, dependence, withdrawal, and abuse.
• Opioid side effects: nausea, pruritus, constipation, headache, opioid-induced hyperalgesia, sedation, respiratory depression, and death.
• Non-opioid effects: risk of seizures and serotonin syndrome especially when used with other drugs that act on the serotonergic system such as monoamine inhibitors.
• Tramadol can cross the placenta and should be minimized in pregnancy to prevent fetal opioid exposure.

References