A. Morphine is primarily conjugated to morphine-3-glucuronide (which has neuroexcitatory properties). Approximately 10% is metabolised to morphine-6-glucuronide (an active metabolite with a much greater analgesic potency than morphine, especially when the blood brain barrier is bypassed -eg. for intrathecal of intraventricular administration in animal models there is 100 times greater potency for M6G).
Katzung, Basic & Clinical Pharmacology, 2002, p400
Goodman & Gilman, Pharmacologic Basis of Therapeutics, 1996, p535
B. Half Life of Various opioids:
Opioid Plasma Half Life
Heroin 0.5 hours
Morphine 2 hours
Hydromorphone 2-3 hours
Oxymorphone 2-3 hours
Codeine 2-4 hours
Fentanyl 3-4 hours
Pethidine 3-4 hours
Methadone 15-40 hours
Goodman & Gilman, Pharmacological Basis of Therapeutics, 1996, p535
The question refers to the half-lives of the metabolites, which are longer than morphine. Stoelting appears to suggest that M-6-G, and M-3-G hang around for days
C. Morphine-6-glucuronide is renally excreted (therefore can accumulate in renal impairment). Elimination by glomerular filtration primarily as morphine-3-glucuronide. Enterohepatic circulation of morphine and it's glucuronides occurs, therefore small amounts can be found in faeces and urine for several days after the last dose.
Goodman & Gilman, Pharmacological Basis of Therapeutics, 1996, p535
Hepatic oxidative metabolism is primary route of degredation for fentanyl/ alfentanil/ sufentanil and eventually leaves only small quantities for excretion. Codeine, oxycodone, hydrocodone all undergo metabolism in the liver.
Katzung, Basic and Clinical Pharmacology, 2004, p499
"Stoelting says that morphine is metabolised principally by conjugation to glucuronic acid, in hepatic and extrahepatic sites, primarily the kidney"
also says "renal metabolism makes a significant contribution"
D. Morphine-3 + Morphine-6 glucuronide both have limited ability to cross the blood brain barrier.
Katzung, Basic and Clinical Pharmacology, 2004, p499
E. Morphine-6 accounts for a significant proportion of morphine's analgesic actions due to higher potency and higher concentrations. Goodman & Gilman, Pharmacological Basis of Therapeutics, 1996, p535
M-3-G has no analgesic properties however
F. "Sulfation is an important pathway for the elimination of acetaminophen and of morphine in neonates." Evers and Maze 2004 p.69
G. See A above.
H Is correct.
Comment: re option E, Evers and Maze (2004) have this to say about morphine 6 glucuronide "It is not clear from clinical studies whether M6G contributes significantly to the opioid effect of a single dose of morphine." but it probably "...accumulates over time." (p465)
