Clinical Pharmacokinetics of Morphine

Question: Discuss about the Clinical Pharmacokinetics of Morphine. Answer: Introduction: Morphine is a highly potent, commonly used opioid analgesic commonly used to treat moderate to severe pains. The information needed about it before administering it to Matt includes: Absorption Dosage of morphine can be administered to matt in the form of oral solution, tablets, capsules, pellets, Intravascular and Intravenous injections, Subcutaneous injections, inhalation, spinal injections and epidural. At times morphine is also administered rectally to be absorbed by rectal blood vessels. In terms of absorption, Morphine is variably absorbed, usually with a 30% efficiency when administered orally. It is efficiently absorbed through gastro-intestinal mucosa. Transdermal absorption of Morphine are however not that effective. After epidural administration, Morphines systemic absorption as well as absorption into the intrathecal space of meninges occurs (Mandal, 2013). Distribution Morphine has a large volume of distribution and hence is quickly distributed throughout the body including the brain. Almost one-third of the drug binds to the plasma protein to facilitate this diffusion. It takes around 15-20 min via IV and IM injections while oral administration takes 30-90 mins to reach peak plasma levels. Morphine undergoes extensive Hepatic First-pass effect reducing its bioavailability substantially (Morphine, n.d. a). Metabolism The metabolism of morphine occurs majorly in liver in a process known as first-pass metabolism as a result of which, 40-50% morphine reaches CNS. Due to its hepatic metabolism, the dosage administered to hepatic patients should be proportionately reduced. The main metabolic pathway to breakdown morphine is glucuronidation through which a number of active and inactive metabolites such as morphine-3-glucuronide (M3G) (inactive), Morphine-6-glucuronide (M6G) (active) are formed. Small quantities of Normorphine (neurotoxic), codeine and hydromorphone may also form (Glare Walsh, 1991). Excretion Morphine and its metabolites are excreted through kidneys after metabolism. In case of renal insufficiency, the metabolites especially M6G tends to accumulate in the body though pure form is released which forms around 10% of administered dose. Pharmacodynamics After entering blood stream, morphine quickly crosses blood-brain barrier and binds predominantly to mu-opioid receptors however simultaneous interaction with Kappa- and delta-type opioid receptors too happen though not to the similar extent. This leads to analgesia, sedation and respiratory depression. Analgesia is induced by binding to the opioid receptors and inhibition of GABA inhibitory neurons which normally inhibit the descending pain inhibition pathway. Without the presence of these GABA neurons, pain modulation happens efficiently. Due to its action on CNS, morphine is administered carefully to mental patients, CNS patients and those administered with MAO inhibitors in the last fortnight (Morphine, n.d. b). References Glare, P. A., Walsh, T. D. (1991). Clinical pharmacokinetics of morphine. Therapeutic drug monitoring, 13(1), 1-23. Mandal, A. (2013). Morphine Pharmacokinetics. News Medical Lifesciences. Retrieved from https://www.news-medical.net/health/Morphine-Pharmacokinetics.aspx Morphine (n.d. a). Davids Drug Guide. Nursing Central. Retrieved from https://nursing.unboundmedicine.com/nursingcentral/view/Davis-Drug-Guide/51518/all/morphine#10 Morphine (n.d. b). The Drug Bank. Retrieved from https://www.drugbank.ca/drugs/DB00295