| Indication |
For the relief of moderate to severe pain such as that due to surgery, cancer, trauma/injury, or burns. |
| Pharmacodynamics |
Hydromorphone is a hydrogenated ketone derivative of morphine
that acts as a narcotic analgesic. It has a shorter duration of action
than morphine. Hydromorphone is approximately 8 times more potent on a
milligram basis than morphine. In addition, hydromorphone is better
absorbed orally than is morphine. In clinical settings, Hydromorphone
exerts its principal pharmacological effect on the central nervous
system and gastrointestinal tract. Its primary actions of therapeutic
value are analgesia and sedation. Hydromorphone 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 |
Hydromorphone is a narcotic analgesic; its principal therapeutic
effect is relief of pain. Hydromorphone interacts predominantly with the
opioid mu-receptors. 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,
Hydromorphone exerts its principal pharmacological effect on the central
nervous system and gastrointestinal tract. Hydromorphone also binds
with kappa-receptors which are thought to mediate spinal analgesia,
miosis and sedation. |
| Absorption |
Better absorbed orally than morphine |
| Volume of distribution |
Not Available |
| Protein binding |
20% |
| Metabolism |
Primarily hepatic. After absorption hydromorphone is metabolized
by the liver to the glucuronide conjugate which is then excreted in the
urine. Hydromorphone is metabolized to the major metabolites
hydromorphone-3-glucuronide, hydromorphone-3-glucoside and
dihydroisomorphine-6-glucuronide. |
| Route of elimination |
Only a small amount of the hydromorphone dose is excreted unchanged in the urine.
Most of the dose is excreted as hydromorphone-3-glucuronide along with minor amounts of 6-hydroxy reduction metabolites. |
| Half life |
2.6 hours (oral); 18.6 hours for sustained release Palladone |
| Clearance |
|
| Toxicity |
Hydromorphone is a schedule II narcotic which can lead to physical
dependence or addiction. High doses lead to respiratory depression,
nausea, and vomiting. Overdoses lead to extreme somnolence progressing
to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and
sometimes bradycardia and hypotension. In severe overdosage, apnea,
circulatory collapse, cardiac arrest and death may occur. |
