Summary of Common Opioids

Opioid Morphine Oxycodone Fentanyl Alfentanil Remifentanil Pethidine

Chemistry Phenanthrene Phenanthrene Phenylpiperidine Phenylpiperidine Phenylpiperidine Phenylpiperidine
Dose equivalent (i.v.) 10 mg 15 mg 100 microg 1 mg 100 microg 100 mg
Absorption
Routes IV/IM/SC IV IV IV IV IV/IM
IT/ED,PO,PR,TOP PO IT/ED,PO,IN,TOP PO
Bioavailability (oral) 20 ~ 30% 60 ~ 80% 30% - - 50%
Distribution
Vd (steady state) ‡ 3.5 L/kg 2.5 L/kg 4 L/kg 0.4 L/kg 0.2 L/kg 4 L/kg
pKa‡ 8.0 8.5 8.4 6.5 7.1 8.5
%unionised (pH=7.4) 23% 7% 10% 90% 67% 5%
§
Relative lipid sol. 1 ~1 600 90 20 30
Protein binding§ 35% 45% 83% 90% 70% 60%
t(iv peak effect) 19 min 5 ~ 10 min (?) 4 min 2 min 1 ~ 2 min 6 min
Metabolism
Site hepatic + extra- CYP3A4 (major) CYP 3A4 CYP 3A4 plasma and tissue hepatic CYP
hepatic (renal) CYP2D6 (minor) esterases
Opioid Morphine Oxycodone Fentanyl Alfentanil Remifentanil Pethidine
Metabolites glucuronidation: demethylation: demethylation: N-dealkylation: remifentanil acid demethylation:
M3G (70%) - inactive noroxycodone (3A4) norfentanyl (inactive) noralfentanil (essentially inactive) norpethidine (90%,
M6G (10%) - active oxymorphone (2D6) (inactive) active)
demethylation: N-phenyl- ! norpethidinic acid
nomorphine (5%) propionamide hydrolysis:
codeine pethidinic acid
Elimination
Renal 1 ~ 2% parent 15% parent minimal < 0.5% parent∆ – pH dependent (acidic
urine ! more parent)
25% parent (@ pH 5)
Clearance 16 mL/kg/min 7 mL/kg/min 13 mL/kg/min 6 mL/kg/min 40 mL/kg/min 12 mL/kg/min
∆
t1/2 2 ~ 4 hrs 3 ~ 4 hrs 2 ~ 4 hrs 1.5 hrs 6 min 3 ~ 5 hrs
CSHT (4 hr infusion) – – 4 hrs 60 min§ 4 min∆ –
Pharmacodynamics
Special properties histamine release muscle rigidity muscle rigidity muscle rigidity anticholinergic
sphincter of Oddi LA effects
spasm w/d start 2~6 hrs addictive +++
w/d start 6~12 hrs w/d duration 4~5 d norpethidine !
w/d duration 7~10 d induces seizures
w/d same as fentanyl

‡ = Miller § = Peck and Hill ∆ = Stoelting 5th