Pharmacokinetics of morphine and its glucuronides following intravenous administration of morphine in patients undergoing continuous ambulatory peritoneal dialysis

Abstract

Accumulation of M3G and M6G is due to the substantially lowered clearance by residual renal function and peritoneal dialysis. In view of the accumulation of potential active metabolites, subsequent investigations have to assess the frequency of side-effects in patients on CAPD.

Induction of morphine-6-glucuronide synthesis by heroin self-administration in the rat

“…Morphine-6-glucuronide has been shown, for example, to produce analgesia when administered systemically (Romberg et al 2004, Skarke et al 2003 and is now under development as a therapeutic agent (Binning et al 2011). Furthermore, central nervous system-depressant effects produced by repeated morphine administrations in patients with renal failure have been attributed to increased high blood levels of M6G due to impaired excretion (Pauli-Magnus et al 1999;Peterson et al 1990). M6G may also be implicated in the well-known individual differences in the responsiveness to morphine.…”

A Clinical Study on Administration of Opioid Antagonists in Terminal Cancer Patients: 7 Patients Receiving Opioid Antagonists Following Opioids among 2443 Terminal Cancer Patients Receiving Opioids

“…35) An interesting outcome of this study is the short survival time after opioid antagonist administration, of which the median value was 5 (3-10) d. Based on this study and a study by Kim et al about the survival time of terminal cancer patients with dyspnea, it is suggested that life prognosis with dyspnea is shorter than expected in terminal cancer patients. 36) Patients who received opioid antagonists in this study had PPS of 20 (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) before the onset of respiratory depression. This suggests that they may have been in the near-death period in which pathological conditions have been exacerbated, as compared with the day before the start of opioid administration, and were developing organopathy.…”

“…The characteristics of these patients were as follows: age, 74±5 years; height, 162±11 cm; body weight, 49.3±5.2 kg; BMI, 18.7±0.8 kg/m 2 ; and PPS, 20 (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). These 7 patients consisted of 4 with lung cancer, 1 with stomach cancer, 1 with pancreatic cancer, and 1 with rectal cancer.…”

“…6) Previous studies demonstrated that risk factors for opioid-induced respiratory depression included opioid overdose, advanced age, sleep apnea, chronic obstructive pulmonary disease, congestive heart failure, renal failure, and hemodialysis/peritoneal dialysis. [7][8][9][10][11][12][13][14] However, the patients in these studies were not terminal cancer patients. In general, opioids rarely induce serious respiratory depression, when used properly in the treatment of pain relief.…”

Opioide in der An�sthesie bei Leber- und Niereninsuffizienz

“…M6G hat eine höhere analgetische Potenz als Morphin selbst, sein Metabolit M3G dagegen zeichnet sich durch eine antianalgetische Wirkung aus.Patienten mit einer chronischen Niereninsuffizienz zeigen nach Bolusgabe von Morphin eine reduzierte Plasmaclearance und ein reduziertes Verteilungsvolumen[32],beides wird durch ein funktionierendes Nierentransplantat normalisiert. Die Plasmahalbwertszeit bleibt bei Niereninsuffizienz interessanterweise unverändert,wohingegen es zu einer deutlichen Akkumulation von M3G und M6G[34] kommt. Inwiefern diese Metabolite zu einer verlängerten atemdepressorischen Wirkung führen, ist derzeit nicht geklärt.Morphin kann aufgrund dieser Ergebnisse bei Patienten mit schwer eingeschränk-ter Leber-und Nierenfunktion nicht empfohlen werden.Piritramid ist ein reiner µ-Agonist, der in der Anästhesie und in der postoperativen Schmerztherapie häufig angewendet wird.Die analgetische Potenz ist vergleichbar mit der von Morphin.Piritramid besitzt das größte Verteilungsvolumen aller gebräuchlichen Opioide[26].…”