Generic Name

Ultram

Brand Names

for tramadol hydrochloride) is a synthetic opioid analgesic that modulates pain through a dual mechanism of action.

Mechanism

• Partial μ‑opioid receptor agonist – provides analgesia by inhibiting nociceptive signal transmission in the CNS.
• Inhibition of serotonin and norepinephrine reuptake – enhances descending inhibitory pain pathways and augments opioid effect.
• The combination yields moderate analgesic potency with a lower risk of tolerance compared to pure μ‑agonists.

Pharmacokinetics

• Administration: Oral (tablet, capsule, liquid), IV (rare), subcutaneous (rare).
• Absorption: Rapid; peak plasma concentration (Tmax) 1–2 h post‑dose.
• Bioavailability: ~66 % (oral); IV = 100 %.
• Distribution: Extensive; volume of distribution (Vd) ~1 L/kg; highly protein‑bound (~80 %).
• Metabolism: Hepatic via CYP2D6 → O‑desmethyltramadol (active metabolite); secondary CYP3A4 → N‑desmethyltramadol (inactive).
• Poor CYP2D6 metabolizers: ↓ analgesia; ultra‑rapid metabolizers: ↑ risk of adverse effects.
• Elimination: Renal (≈50 % unchanged; 30 % as metabolites).
• T1/2: 3–4 h (tramadol), 7–9 h (O‑desmethyltramadol).

Indications

• Acute pain: Post‑operative, dental, trauma, musculoskeletal injuries.
• Chronic non‑cancer pain: Osteoarthritis, neuropathic pain (when other agents inadequate).
• Relief of breakthrough pain in patients already on chronic opioid therapy.

Contraindications

• Absolute Contraindications:
• Known hypersensitivity to tramadol or any excipients.
• Severe respiratory depression or untreated severe asthma.
• Severe hepatic or renal impairment (dose adjustment required).
• Concurrent use with monoamine oxidase inhibitors (MAOIs).
• Precautions:
• Elderly patients; risk of falls, sedation, respiratory depression.
• Pregnant & lactating women (Category C).
• Concomitant serotonergic agents → risk of serotonin syndrome.
• Drug Interactions:
• SSRIs, SNRIs, MAOIs, fenfluramine, linezolid, carbamazepine, phenytoin → ↑ tramadol levels.
• NSAIDs, SSRIs → ↑ bleeding risk.

Dosing

• Formulations: Tablet, capsule, oral suspension, IV infusion (1.5 mg/kg/h).
• Administration tips: Take after meals to reduce nausea; avoid alcohol.

Adverse Effects

Monitoring

• Vital Signs: Respiratory rate, oxygen saturation, level of consciousness (especially in the first 24 h of therapy or after dose increase).
• Laboratory: Renal function (CrCl), hepatic panels if prolonged use.
• ECG: QT interval if concomitant QT‑prolonging agents.
• Patient‑Reported: Pain score, sedation level, nausea.
• Screen for Serotonin Syndrome: agitation, autonomic instability, neuromuscular abnormalities when combined with serotonergic drugs.

Clinical Pearls

• CYP2D6 Genotyping Matters:
• Poor metabolizers: Provide alternative analgesics (e.g., NSAIDs, scheduled opioids).
• Ultra‑rapid metabolizers: Consider lower dose and monitor for seizures/over‑analgesia.
• Avoid Abrupt Discontinuation:
• Use a gradual taper to prevent withdrawal symptoms; consider bridging agent like gabapentin for neuropathic pain.
• Pregnancy & Lactation:
• Use only if benefits outweigh risks; avoid high doses; prefer paracetamol or ibuprofen for mild pain.
• Serotonin Syndrome Warning:
• Symptoms appear within hours of adding a serotonergic drug to tramadol; discontinue tramadol and treat supportively if suspected.
• Opioid‑Safe Use:
• Encourage non‑opioid adjuncts (acetaminophen, NSAIDs, duloxetine) to reduce total opioid exposure.
• Non‑Pain Indications:
• Tramadol can treat neuropathic pain and osteoarthritis; dose adjustments may be required due to its norepinephrine reuptake inhibition.
• Drug Interaction Alert:
• Carbamazepine and phenytoin can *induce* tramadol metabolism → sub‑therapeutic analgesia.
• SSRIs can *potentiate* tramadol → ↑ respiratory depression risk.
• Clinical Scenario – Elderly:
• Start at the lowest dose (25 mg q6‑8 h) and titrate cautiously; monitor for falls and sedation.
• When to Escalate:
• If pain remains uncontrolled despite maximal doses, consider opioid rotation or multimodal analgesia rather than simply increasing tramadol dose.

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• Ultram (tramadol) remains a versatile analgesic when used judiciously, with careful patient selection, dose titration, and monitoring to mitigate its unique pharmacologic and safety profile.