Pain
Other Opiates:
Oxycodone:
- Oxycodone oral bioavailability is higher than morphine so it is about 1.5 times more potent than morphine(3).
- Metabolism is via Cytocrome P450.
- Renal and hepatic elimination and has active metabolites.
Codeine:
- Metabolism is via Cytocrome P450 and its analgesic effect is through bio-transformation to morphine.
- Some researchers have proposed that codeine is a pro-drug with analgesic activity dependent on its conversion to morphine by the cytochrome P-450 2D6 (CYP2D6) enzyme.(9)
- Additionally, up to 10% of the population lack the CYP2D6 enzyme and may not achieve analgesia with codeine-containing products (10) for this reason it is not used in palliative care.
- Elimination route is renal and caution in patients with renal failure should be considered.
Methadone
- Methadone acts as an agonist of mu and delta opioid receptors, has N-methyl-aspartate (NMDA) receptor anatagonist actions.
- The NMDA mechanism is thought to play a role in the prevention of opioid tolerance, potentiation of the opioid analgesic effect and potentially role in neuropathic pain (3).
- The half life can be as long as 190 hours and a steady state may take 2-10 days to achieve. (3)
- Methadone’s longer half-life means that it stays in the body longer than other opioids and thus plasma levels build up quicker than might be realized. (11) Therefore delayed sedation and potentially life threatening respiratory depression can be seen if methadone is not titrated properly.
- Methadone is lipophilic and distributes widely in the body. No clear relationship is seen between plasma concentrations of methadone and its analgesic effect.
- Methadone metabolite is inactive, so does not accumulate in renal failure and is poorly removed by hemodialysis (12).
Table 4. Adapted from Dosing Guideline for Methadone in Children, (H.Siden) (3)
Route |
Younger Child < 50 kg |
Older Child > 50 kg |
Comments |
Response Time |
Duration of action |
PO |
Initial dose 0.2 mg/kg/dose every 4-8 hours if opioid naive |
5-10 mg every 4-8 hrs |
Reported half life ranges from 22-55 hrs variation in metabolism-dosing intervals may vary from 4-12 hrs, 8 hrs is common. |
Initial response is 2 hrs for single dose. Time to peak concentration is 2-4 hrs. |
For single dose duration variable: 2-10 hrs. |
PO conversion from another opioid |
Multiple ratios used 10:1 is common. q3h as needed for first 3 days, then convert to q8hrs dose. Some children require q 6 h, very few q 12h. 1.5 mcg/kg/hr continuous infusion titrate to effect |
Many methods. Often use “Sawe” method of patient -response based titration × 3 days |
1-2 min |
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