| Indication |
For the relief of mild to moderate pain |
| Pharmacodynamics |
Propoxyphene, a synthetic opiate agonist, is structurally
similar to methadone. Its general pharmacologic properties are those of
the opiates as a group. The analgesic effect of propoxyphene is due to
the d-isomer, dextropropoxyphene. It binds to the opiate receptors and
leads to a decrease of the perception of pain stimuli. Propoxyphene
possesses little to no antitussive activity and no antipyretic action. |
| Mechanism of action |
Propoxyphene acts as a weak agonist at OP1, OP2, and OP3 opiate
receptors within the central nervous system (CNS). Propoxyphene
primarily affects OP3 receptors, which are coupled with G-protein
receptors and function as modulators, both positive and negative, of
synaptic transmission via G-proteins that activate effector proteins.
Binding of the opiate stimulates the exchange of GTP for GDP on the
G-protein complex. As the effector system is adenylate cyclase and cAMP
located at the inner surface of the plasma membrane, opioids decrease
intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the
release of nociceptive neurotransmitters such as substance P, GABA,
dopamine, acetylcholine, and noradrenaline is inhibited. Opioids such as
propoxyphene also inhibit the release of vasopressin, somatostatin,
insulin, and glucagon. Opioids close N-type voltage-operated calcium
channels (OP2-receptor agonist) and open calcium-dependent inwardly
rectifying potassium channels (OP3 and OP1 receptor agonist). This
results in hyperpolarization and reduced neuronal excitability. |
| Absorption |
Not Available |
| Volume of distribution |
|
| Protein binding |
Not Available |
| Metabolism |
Hepatic |
| Route of elimination |
The major route of metabolism is cytochrome CYP3A4 mediated
N-demethylation to norpropoxyphene, which is excreted by the kidneys.
In 48 hours, approximately 20% to 25% of the administered dose of
propoxyphene is excreted via the urine, most of which is free or
conjugated norpropoxyphene. |
| Half life |
6-12 hours |
| Clearance |
|
| Toxicity |
Coma, respiratory depression, circulatory collapse, and pulmonary
edema. Seizures occur more frequently in patients with propoxyphene
intoxication than in those with opiate intoxication. LD50=230mg/kg (orally in rat, Emerson) |
