- they're metabolized by hepatic glucuronidase to 6-glucurinides (e.g. morphine 6 glucuronide or M6G)
- these metabolites are renally excreted, increasing the half-life to 6 times that of the parent compound in ESRD
- peak toxicity may not occur for over 6 hours (or at 6 am while you're on call) as M6G occurs in both hydrophilic and lipophilic forms, and it takes time for the latter to cross the blood-brain barrier and acculmulate in the CSF. Opiate toxicity should be your first thought in any hypoventilating dialysis patient.
The worst offenders are codeine and morphine, and to a lesser extent oxycodone and hydromorphone. Not all opiates behave like this though, and the following three are probably safest:
- Fentanyl has no active metabolites and appears to be well tolerated.
- Tramadol is a non-narcotic analgesic with some effects at the mu opioid receptor. It's usual half-life is 5 hours, increasing to ten in ESRD. Max. dose of 50mg bid. Watch out for serotonin syndrome with SSRI's
- Methadone does not appear to accumulate at all in renal failure, as observed in drug addicts with CKD and ESRD, and appears safe to use.