| Indication |
For the relief and treatment of severe pain. |
| Pharmacodynamics |
Morphine is a narcotic pain management agent indicated for the
relief of pain in patients who require opioid analgesics for more than a
few days. Morphine interacts predominantly with the opioid mu-receptor.
These mu-binding sites are discretely distributed in the human brain,
with high densities in the posterior amygdala, hypothalamus, thalamus,
nucleus caudatus, putamen, and certain cortical areas. They are also
found on the terminal axons of primary afferents within laminae I and II
(substantia gelatinosa) of the spinal cord and in the spinal nucleus of
the trigeminal nerve. In clinical settings, morphine exerts its
principal pharmacological effect on the central nervous system and
gastrointestinal tract. Its primary actions of therapeutic value are
analgesia and sedation. Morphine appears to increase the patient's
tolerance for pain and to decrease discomfort, although the presence of
the pain itself may still be recognized. In addition to analgesia,
alterations in mood, euphoria and dysphoria, and drowsiness commonly
occur. Opioids also produce respiratory depression by direct action on
brain stem respiratory centers. |
| Mechanism of action |
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. |
| Absorption |
Bioavailability is approximately 30%. |
| Volume of distribution |
|
| Protein binding |
30-40% |
| 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 |
| Clearance |
- 20 – 30 mL/min/kg [Adult]
- 1852 +/- 116 mL/min [Chinese]
- 1495 +/- 80 mL/min [Caucasian]
|
| Toxicity |
LD50 = 461 mg/kg (rat, oral), 600 mg/kg (mouse, oral).
Human lethal dose by ingestion is 120-250 mg of morphine sulfate.
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. |
