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
- Post op analgesia
- 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