Knowledge
Collections with the topic tag Tramadol
-
Tramadol is a synthetic opioid agonist and neurotransmitter-modulating analgesic.
A. Physiochemistry
- Synthetic analgesic of 'amino-cyclo-hexanol' group.
- Racemic mixture of two enantiomers + and -:
- (-) Inhibits NAd reuptake
- (+) Enhances 5HT release, inhibits 5HT reuptake, weak mu (& less kapaa/delta) agonist.
- Oral (50 mg capsules, 100 mg tablets) & parenteral (100 mg/2mL) preparations.
- pKa 9.4
B. Pharmacokinetics
- Dose - 5-10x less potent than morphine: 50-100 mg q6h, max 400-600 mg/day.
- 2-3 mg/kg loading, then 1-2 mg/kg q6h.
- PCA IV tramadol: 20 mg/mL then step down to oral (Prof Schug, Perth: 25-50 mg q1h PCA, using up to 1500 mg/24h).
- analgesic efficacy and potency comparable to pethidine
- Caudal: 2 mg/kg
- Absorption - IV, IM, po (80% biov)
- Distribution - 3 L/kg (80% crosses placenta).
- Protein binding - 20%
- Onset 30 min; Offset 6 h
- peak [plasma] after po: 2h
- Metabolism - t½ 6h (12h in renal impairment);
- 85% p450 (CYP-2D6 - also converts codeine → morphine & metabolises ondansetron!)
- Demethylation to 'O-demethyl-tramadol' (M1) t½ 9h - has some activity as it has 6x greater mu affinity than tramadol. Some consider tramadol a prodrug because of this.
- 90% excreted in urine, 10% in faecies.
- metabolism inhibited by quinidine
- Clearance - 9 mL/kg/min
C. Pharmacodynamics
- Mech - weak mu agonists (30% of action) (very weak kappa & delta); inhibits NAd reuptake (through indirect activation of post-synaptic alpha-2 adrenoreceptors) and stimulates 5HT release, so activates desc NAd and 5HT pathways (70%), modulating pain pathways.
- Naloxone antagonises only 30% tramadol analgesic effect. Ondansetron antagonises a further 30% of tramadol analgesic effect.
- CNS - analgesia, good for neuropathic pain, low(er) incidence of tolerance & dependence, lowers seizure threshold, dizziness, sweating.
- stops shivering?
- CVS - few CVS effects. Some tachycardia and flushing.
- Resp - little respiratory depression.
- Renal - caution in renal failure.
- GIT - Nausea & vomiting (30-40%, like morphine), minimal constipation, minimal biliary spasm.
- SEs - interacts with MAOI, SSRIs.
- Quinidine may decrease efficacy of tramadol by inhibiting CYP-2D6, thus decreasing production of M1. Codeine my compete for the same enzyme with a similar result.
- Carbamazepine induces CYP-2D6 decreasing effect by increasing metabolism.