Tramadol
Tramadol
Generic Name
Tramadol
Mechanism
- Tramadol achieves analgesia primarily through two mechanisms:
* weak μ‑opioid receptor agonism (≈ 5 % affinity)
* inhibition of norepinephrine and serotonin reuptake, boosting descending inhibitory pathways.
• Its active metabolite, O‑desmethyl‑tramadol, accounts for 50–70 % of the drug’s effect and is ~3× more potent at μ‑agonism.
• The SNRI component also augments pain control, making tramadol useful for certain neuropathic pain states.
Pharmacokinetics
- Absorption: Oral bioavailability 60–70 %; Tmax 1–3 h.
- Metabolism: CYP2D6 and CYP3A4 convert tramadol to the active O‑desmethyl metabolite; hepatic clearance ~30–40 %.
- Elimination: 30–45 % unchanged renal excretion; 40–50 % of the metabolite renal.
- Half‑life: 6–7 h (free drug); 8–9 h (metabolite). Short‑half‑life is extended in severe hepatic disease.
- Protein binding: ~80 %; highly lipophilic and crosses the blood–brain barrier efficiently.
Indications
- Moderate‑to‑severe acute pain (post‑operative, traumatic).
- Short‑term management of chronic non‑cancer pain when opioid therapy is required.
- Adjunctive treatment for neuropathic pain in selected patients.
- Not first‑line for cancer pain; reserved for limited or bridging uses.
Contraindications
- Contraindications
* Known hypersensitivity to tramadol or its excipients.
* Severe respiratory depression or significant central nervous system depression.
* Uncontrolled seizure disorders (tramadol lowers the seizure threshold).
• Warnings
* Caution in hepatic or renal impairment—dose adaptation required.
* Serious risk of serotonin syndrome when combined with SSRIs, SNRIs, MAOIs, or linezolid.
* Potential for abuse, tolerance, and physical dependence; monitor for signs of misuse.
* Not recommended for patients with a confirmed CYP2D6 poor‑metabolizer status unless monitored closely.
Dosing
| Patient group | Typical oral dose | Frequency | Max daily dose |
| Adults | 50–100 mg PO q6–8 h PRN | 6–8 h | 400 mg |
| Opioid‑naïve | 25 mg PO q6–8 h | 6–8 h | 200 mg |
| Elderly / hepatic impairment | 25 mg PO q8–12 h | 8–12 h | 150 mg |
| Renal impairment (CrCl <30 mL/min) | 25 mg PO q12–24 h (slow‑release) | 12–24 h | 100 mg |
| IV | 1–2 mg/kg q6–8 h or 10 mg single dose for acute pain | 6–8 h | 30 mg/kg/day |
• No loading dose is necessary.
• Begin at the lowest effective dose; titrate every 12–24 h.
Adverse Effects
- Common: nausea, vomiting, dizziness, constipation, somnolence, headache, dry mouth.
- Serious: respiratory depression (especially in combination with alcohol or other CNS depressants), seizures (especially in poor CYP2D6 metabolizers or when combined with serotonergic drugs), serotonin syndrome (confusion, autonomic instability), hypotension, anaphylaxis.
Monitoring
- Pain scores (numeric rating or VAS).
- Vital signs: BP, HR, RR, SpO₂.
- Sedation/alertness (Riker Sedation‑Agitation Scale).
- Seizure activity, particularly if on serotonergic agents.
- Renal and hepatic panels for dose‑adjustment needs.
- Signs of misuse or withdrawal (tolerance, escalation of dose).
Clinical Pearls
- Assess CYP2D6 phenotype: Poor metabolizers may experience sub‑analgesia and higher seizure risk; consider dose reduction or alternative agents.
- Never combine with serotonergic drugs: A single SSRI or MAOI can precipitate serotonin syndrome; advise discontinuation or substitution.
- Use the lowest effective dose for ≤ 7 days: Minimizes tolerance and dependence.
- Elderly vigilance: Polypharmacy and reduced clearance heighten risk of oversedation and respiratory depression.
- Address constipation proactively: Start a bowel regimen and ensure adequate hydration to prevent tramadol‑associated constipation.
- Cross‑tolerance awareness: Switching directly from a strong opioid to tramadol may under‑address pain; a taper or dose check may be required.
Key take‑away: Tramadol’s dual μ‑agonist and SNRI activity offers versatile pain control for moderate‑to‑severe acute pain, but its pharmacodynamic profile demands careful patient selection, dose titration, and monitoring—particularly in populations at risk for respiratory depression and serotonin syndrome.