Morphine - How It Works
Clinical pharmacology details from the US FDA-approved label: how Morphine works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
12.1 Mechanism of Action Morphine is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of morphine is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with morphine. Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression. The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Morphine is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses.
The principal therapeutic action of morphine is analgesia.
Like all full opioid agonists, there is no ceiling effect for analgesia with morphine.
Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression.
The precise mechanism of the analgesic action is unknown.
However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.
12.2 Pharmacodynamics CNS Depressant/Alcohol Interaction Additive pharmacodynamic effects may be expected when morphine sulfate extended-release tablets are used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression.
Effects on the Central Nervous System Morphine produces respiratory depression by direct action on brainstem respiratory centers.
The respiratory depression involves a reduction in the responsiveness of the brainstem respiratory centers to both increases in carbon dioxide tension and electrical stimulation.
Morphine causes miosis, even in total darkness.
Pinpoint pupils are a sign of narcotic overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings).
Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.
Effects on the Gastrointestinal Tract and Other Smooth Muscle Morphine causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and in the duodenum.
Digestion of food in the small intestine is delayed and propulsive contractions are decreased.
Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm, resulting in constipation.
Other opioid-induced effects may include reduction in biliary and pancreatic secretions, spasm of the sphincter of Oddi, transient elevations in serum amylase, and opioid-induced esophageal dysfunction (OIED).
Effects on the Cardiovascular System Morphine produces peripheral vasodilation which may result in orthostatic hypotension or syncope.
Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension.
Effects on the Endocrine System Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see Adverse Reaction ] .
They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon.
Pharmacokinetics
12.3 Pharmacokinetics Absorption Morphine sulfate extended-release tablets are an extended-release tablet containing morphine sulfate. Morphine is released from morphine sulfate extended-release tablets somewhat more slowly than from immediate-release oral preparations. Following oral administration of a given dose of morphine, the amount ultimately absorbed is essentially the same whether the source is morphine sulfate extended-release tablets or an immediate-release formulation. Because of pre-systemic elimination (i.e., metabolism in the gut wall and liver) only about 40% of the administered dose reaches the central compartment. The oral bioavailability of morphine is approximately 20 to 40%. When morphine sulfate extended-release tablets are given on a fixed dosing regimen, steady-state is achieved in about a day. Food Effect The effect of food upon the systemic bioavailability of morphine sulfate extended-release tablets has not been systematically evaluated for all strengths. One study, conducted with the 30 mg morphine sulfate extended-release tablets, showed no significant differences in C max and AUC (0-24h) values, whether the tablet was taken while fasting or with a high-fat breakfast. Distribution Once absorbed, morphine is distributed to skeletal muscle, kidneys, liver, intestinal tract, lungs, spleen, and brain. Morphine also crosses placental membranes and has been found in breast milk. The volume of distribution (Vd) for morphine is approximately 3 to 4 liters