Tramadol

Chemical

Centrally acting, aminocyclohexidine derivative OPIOID ANALGESIC

With low affinity for µOR, acting primarily by facilitating descending inhibitory monoaminergic pathways

  • Structurally related to M
  • Racemic mixture:
  • Dextro (+) = inhibits 5HT uptake µOR agonist
  • Levo (-) = inhibits NA uptake

Use

  1. Post op analgesia
  2. Chronic pain

Presentation

Tablets 50mg

Ampoule, clear colourless

50mg/mL

Dose

50 – 100mg QID

Route

PO/IV/IM

Onset

30 mins → peaks in 2hrs

SR → onset 60 mins, peaks 5hrs

MoA

Acts differently to traditional opioids

  • 1/3 = µOP agonism
  • 2/3 = facilitates descending inhibitory monoaminergic pathways from Br → Dorsal Horn
  • At Dorsal Horn NA produces analgesia by α2 postsynaptic agonism
    • Inhibits NA & 5HT reuptake
    • More NA for α2 agonism
    • Pain perception involves NA & 5HT descending pathways

PD

CNS – analgesia (equivalent to pethidine)

  • Minimal CVS/Resp effects

GI – N&V high incidence, low incidence constipation

PK

A

100% OBA

D

VD 5L/kg

PPB 20% (low cf. opioids)

Crosses placenta

M

Demethylation in liver

1° active metabolite is MONO-O-DESMETHYLTRAMADOL

This metabolite has greater µOP affinity cf. tramadol itself

E

Renal metabolite excretion

<1% bile

20% unchanged

Demethylation by P450 enzymes

  • P450 2D6 → the enzyme also responsible for converting codeine → morphine
  • P450 3A4 → but main enzyme is 2D6

Drug Interactions

SSRI/MAOI/NSRI

*** Can precipitate Serotonin Syndrome

Adverse Effects

  • Dizziness, uncoordination, headache
  • N&V biggest problem (5HT released → activates CTZ vomiting centre)
  • Low abuse potential