Collections with the topic tag Tapentadol
Tapentadol (Paliex™, Nucynta™) is a synthetic opioid agonist and noradrenaline-reuptake inhibitor. Similar to and based upon tramadol, although with much weaker inhibition (by design) of serotonin reuptake.
- Synthetic analgesic of 'amino-cyclo-hexanol' group.
- Unlike tramadol, prepared as only the (R,R) stereoisomer (weakest opioid activity).
- Oral: 50, 75 & 100 mg immediate release, and 50,100,150 & 200 mg extended release preparations.
- No parenteral preparation is approved for use.
- Dose: 50-200 mg bd/qid for immediate release preparations, 50-200mg bd for extended release.
- approximately double potency of tramadol, similar to oxycodone and between tramadol and morphine.
- Absorption - po (only 32% biov)
- increasing doses have a non-linear effect on increasing peak plasma concentration, thus higher doses result in disproportionately higher Cmax.
- Distribution - ~8 L/kg (higher than tramadol).
- Protein binding - 20% (low!)
- Onset 30 min; Offset 4-6 h
- Metabolism - t½ 4h
- hepatic conjugation with glucuronic acid → glucuronides is main pathway (tapentadol-O-glucuronide); p450 metabolism to N-desmethyl tapentadol and hydroxyl tapentadol.
- No known active metabolites
- 99% excreted in urine, 1% in faecies.
- Clearance - 22 mL/kg/min
- Mech - weak mu agonists (30% of action / 18x less affinity than morphine) ; inhibits NAd reuptake (through indirect activation of post-synaptic alpha-2 adrenoreceptors), activating descending NAd (70%) modulating pain pathways.
- CNS - analgesia, good for neuropathic pain, low(er) incidence of tolerance & dependence, lowers seizure threshold, dizziness, sweating, ⇡ ICP.
- CVS - few CVS effects. Some tachycardia and flushing.
- Resp - little respiratory depression.
- Renal - possible caution in renal failure, although no active metabolites even if 99% renal excreted.
- GIT - Nausea & vomiting (less than tramadol), minimal constipation, more biliary spasm than tramadol.
- SEs - interacts with MAOI (adrenergic storm), SSRIs (serotonin syndrome).
- Although thought to have less abuse potential than other common opioids, it is still classed as a Schedule 2 drug in the US, Schedule 1 in Canada, Class A controlled drug in the UK and S8 in Australia.
- Safety of tapentadol in pregnant, lactating women, and pediatric patients is not yet established.