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Palliative care
Published in Peter Hoskin, Peter Ostler, Clinical Oncology, 2020
Morphine is converted in the liver to morphine 3 glucuronide and morphine 6 glucuronide, the latter being a potent analgesic. In renal failure, there is an accumulation of the morphine glucuronides resulting in significant toxicity. Morphine is therefore contraindicated in patients with impaired renal function.
Opioids Analgesics and Antagonists
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
R. Rachana, Tanya Gupta, Saumya Yadav, Manisha Singh
In the process of metabolization of morphine, it undergoes phase-I metabolism and phase-II metabolism. After the morphine has been administered to the patients via nebulizer or is taken orally, subcutaneously or intravenously, under phase-I metabolism, it is majorly metabolized via oxidation or hydrolysis in the liver and leads to the alteration in plasma levels. After this stage only, 40–50% of the morphine spreads to the CNS and within 72 h. 80% morphine dose is excreted via urine (Trescot et al., 2008). Then it undergoes, phase-II metabolism where it is metabolized by glucuronidation that is, the transfer of glucuronic acid component of uridine diphosphate glucuronic acid to a substrate in the presence of UDP-glucuronosyltransferase. The metabolizing process leads to synthesis of morphine-3-glucuronide and morphine-6-glucuronide in a ratio of 6:1 (Lotsch and Geisslinger, 2001), which are the two important metabolic morphine pathways in humans. The principal enzyme for morphine metabolism is UGT2B7 [uridine diphosphoglucuronosyl transferases (UGT)] which is primarily released by liver, but can be released by brain and kidneys, as well (Chau et al., 2014) However, the meaningful clinical effect of hydromorphone metabolite of morphine is still unknown (Fig. 19.2).
Local Anesthetics and Additives
Published in Bernard J. Dalens, Jean-Pierre Monnet, Yves Harmand, Pediatric Regional Anesthesia, 2019
Jean-Pierre Haberer, Bernard Jacques Dalens
Morphine-6-glucuronide is a minor metabolite in man under normal circumstances, but it has been reported to produce prolonged analgesic effects in animals when injected by various routes (including systemic administration).128 Both morphine-3-glucuronide and morphine-6-glucuronide are able to produce narcotic effects when they are injected directly into the central nervous system.128 This must be kept in mind when high blood levels of drug are maintained for long periods, since even the most polar compound can penetrate any membrane barrier, including the blood/brain barrier.
Research progress of p38 as a new therapeutic target against morphine tolerance and the current status of therapy of morphine tolerance
Published in Journal of Drug Targeting, 2023
In 1806, Friedrich Serturner, a German pharmacist, isolated a water-soluble alkaloid from the dry juice of immature seeds of opium poppy and named it morphine [15]. Since then, morphine has been known to be poorly soluble in lipids. After systemic administration, morphine binds to a variety of proteins, including uridine diphosphate glucuronosyltransferase family 2 member B7 (UGT2B7), organic cation transporter isoform 1 (OCT1), histidine triad nucleotide-binding protein 1 (HINT1), opioid receptor mu 1 (OPRM1) and p-glycoprotein (p-gp) [16–19]. About 90% of morphine is converted into metabolites. Morphine is mainly converted to morphine-3-glucuronoside (M3G) (45–55%) and morphine-6-glucuronoside (M6G) (10–15%) in the liver, the brain, and the kidney through the second stage of glucuronidation. Each metabolite plays its pharmacological role within the human body. M3G has a low affinity for opioid receptors and has no analgesic activity. M6G binds to 20]. Some studies have found that morphine metabolites are also related to morphine tolerance and the formation of pain sensitivity. The analgesic effect of morphine increased in a concentration-dependent manner, but the antinociceptive effect decreased with the increase of plasma M3G concentration (1.0–2.521]. The metabolic level of M6G in the body is very low, but its activity is high, which may be one of the reasons for morphine resistance [22].
Comparison of lower-dose versus higher-dose intravenous naloxone on time to recurrence of opioid toxicity in the emergency department
Published in Clinical Toxicology, 2019
Felicia Wong, Christopher J. Edwards, Daniel H. Jarrell, Asad E. Patanwala
In a pharmacokinetic–pharmacodynamic modeling study, 56 health volunteers were administered IV morphine or morphine-6-glucuronide, followed by either placebo or escalating doses of naloxone at 30 minutes [6]. Breathing was measured before and up to 120 minutes after drug administration. The results showed a greater duration of reversal with the higher dose of naloxone as measured by ventilation. The dose of IV morphine administered in this study was 0.15 mg/kg, which induces some respiratory depression. However, it is difficult to extrapolate these findings to the ED setting in patients with profound overdose who have taken large doses of opioids.
The relationship between antemortem and postmortem morphine concentrations
Published in Clinical Toxicology, 2019
Nigel J. Langford, Stephen R. Morley, Robin E. Ferner
Our subjects were generally older patients with multiple comorbidities including renal impairment: the mean eGFR was 47 mL/min/1.73 m2 (range 15–90 mL/min/1.73 m2). They had received different doses of morphine prior to their death via a variety of routes. There is no agreed therapeutic range for morphine, as the unconjugated and glucuronides (M6G) morphine can both have clinical effects, and there is such a large variation in the pharmacokinetics and pharmacodynamics of pain relief. The antemortem total morphine concentrations in the samples we examined ranged from 5 μg/L to 611 μg/L.