• Metabolism: Primarily hepatic (90%), converted to dihydromorphinone and normorphine. Also converted to morphine-3-glucuronide (M3G) and morphine-6-glucuronide. Virtually all morphine is converted to glucuronide metabolites; only a small fraction (less than 5%) of absorbed morphine is demethylated. Route of Elimination: A small amount of glucuronide conjugates are excreted in bile, with minor enterohepatic recycling. Seven to 10% of administered morphine sulfate is excreted in the feces. Half Life: 2-4 hours
• Uses/Sources: For the relief and treatment of severe pain.
• Health Effects: Medical problems can include congested lungs, liver disease, tetanus, infection of the heart valves, skin abscesses, anemia and pneumonia. Death can occur from overdose.
• Symptoms: Symptoms of overdose include cold, clammy skin, flaccid muscles, fluid in the lungs, lowered blood pressure, "pinpoint" or dilated pupils, sleepiness leading to stupor and coma, slowed breathing, and slow pulse rate.
• Treatment: In the treatment of morphine overdosage, primary attention should be given to the re- establishment of a patent airway and institution of assisted or controlled ventilation. Supportive measures (including oxygen, vasopressors) should be employed in the management of circulatory shock and pulmonary edema accompanying overdose as indicated. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation. The pure opioid antagonists, such as naloxone, are specific antidotes against respiratory depression which results from opioid overdose. Naloxone should be administered intravenously; however, because its duration of action is relatively short, the patient must be carefully monitored until spontaneous respiration is reliably re-established. If the response to naloxone is suboptimal or not sustained, additional naloxone may be administered, as needed, or given by continuous infusion to maintain alertness and respiratory function; however, there is no information available about the cumulative dose of naloxone that may be safely administered. (L1712)
• Route of Exposure: Intravenous, Topical, Oral, Intramuscular, Epidural, Rectal. Bioavailability is approximately 30%.

• Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
• Toxicity: LD50: 461 mg/kg (oral, rat) LD50: 600 mg/kg (oral, mouse)
• Lethal Dose: Human lethal dose by ingestion is 120-250 mg of morphine sulfate.

The precise mechanism of the analgesic action of morphine is unknown. However, specific CNS opiate receptors have been identified and likely play a role in the expression of analgesic effects. Morphine first acts on the mu-opioid receptors. The mechanism of respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to increases in carbon dioxide tension and to electrical stimulation. It has been shown that morphine binds to and inhibits GABA inhibitory interneurons. These interneurons normally inhibit the descending pain inhibition pathway. So, without the inhibitory signals, pain modulation can proceed downstream.