Active ingredient: Propoxyphene - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Narcotics
• Antitussives
• Analgesics

Dosage Forms

• Tablet

Brands / Synonyms

Algafan; Antalvic; D-Propoxyphene; Darvocet; Darvocet-N; Darvon; Darvon-N; Deprancol; Depromic; Dextropropoxyphene; Dextropropoxyphene-M; Dextroproxifeno; Dolene; Dolocap; Doloxen; Doloxene; Erantin; Femadol; Harmar; Kesso-Gesic; Propacet; Prophene 65; Propoxychel; Propoxyphene and Acetaminophen; Propoxyphene HCl; Propoxyphene HCl 65; Propoxyphene Napsylate and Acetaminophen; Proxagesic

Indications

For the relief of mild to moderate pain

Pharmacology

Propoxyphene, a synthetic opiate agonist, is structurally similar to methadone. 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.

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

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)

Biotrnasformation / Drug Metabolism

Hepatic

Contraindications

Hypersensitivity to propoxyphene.

Drug Interactions

The CNS-depressant effect of propoxyphene is additive with that of other CNS depressants, including alcohol.

As is the case with many medicinal agents, propoxyphene may slow the metabolism of a concomitantly administered drug. Should this occur, the higher serum concentrations of that drug may result in increased pharmacologic or adverse effects of that drug. Such occurrences have been reported when propoxyphene was administered to patients on antidepressants, anticonvulsants, or warfarin-like drugs. Sever neurologic signs, including coma, have occurred with concurrent use of carbamazepine.