2. Prepared by: Maha Al-Mazyed Propoxyphene

3. Darvon® Compound-65 Pulvules® Darvon-N® E-Lor® PC-CAP® Wygesic® Brand names

4. Propoxyphene Propoxyphene is a mild narcotic analgesic structurally related to methadone. The potency of propoxyphene hydrochloride is from two-thirds to equal that of codeine. CLASS:

5. Propoxyphene Odorless white crystalline powder bitter taste freely soluble in water DESCRIPTION

6. (2S,3R)-(+)-4-(Dimethylamino)-3-methyl-1,2-diphenyl-2- butanol propionate (ester) hydrochloride. Chemical structure:

7. For the relief of mild to moderate pain INDICATIONS

8. dizziness drowsiness upset stomach vomiting constipation stomach pain skin rash mood changes headache difficulty breathing SIDE EFFECTS

9. Respiratory depression. cyanosis and hypoxia. Pupils, initially pinpoint, may become dilated as hypoxia increases. blood pressure falls and cardiac performance deteriorates, which results in pulmonary edema and circulatory collaps A combined respiratory-metabolic acidosis occurs, Acidosis may be severe if large amounts of salicylates have also been ingested. Death may occur. Symptoms of Overdosage:

10. Attention should be directed first to establish airway and to restoring ventilation. Mechanically assisted ventilation, with or without oxygen, may be required positive pressure respiration may be desirable if pulmonary edema is present. The narcotic antagonist naloxone will markedly reduce the degree of respiratory depression Treatment of Overdosage:

11. Drug Abuse and Dependence Propoxyphene, when taken in higher-than- recommended doses over long periods of time, can produce drug dependence characterized by psychic dependence Less frequently, physical dependence and tolerance. Partially suppress the withdrawal syndrome in individuals physically dependent on morphine or other narcotics.

12. Drug Abuse and Dependence Count. The abuse liability of propoxyphene is qualitatively similar to that of codeine although quantitatively less. Do not stop taking propoxyphene suddenly if you have been taking it continuously for more than 5 to 7 days. Stopping suddenly could cause withdrawal symptoms and make you very uncomfortable.

13. determination of propoxyphene and norpropoxyphene in plasma and breast milk. The compounds were isolated from the biological specimen by extraction, the organic phase was evaporated to dryness The residue was redissolved in mobile phase [acetonitrile: 0.002 M H2SO4 (1:1)]. The resultant solution was then injected into an HPLC system utilizing a C18 reversed-phase analytical column and a variable-wavelength detector set at 205 nm. Under these conditions the method has a sensitivity of 20 ng/mL using 1 mL of plasma or milk. Analysis: High-performance liquid chromatographic (HPLC):

14. Rapid, accurate, and precise method for measurement of propoxyphene in serum. A sample of 5 ml of serum is required for quantitation in blood after a therapeutic dose of 130-195 mg In cases of overdose of propoxyphene, only 1 ml of serum is required in a “toxic method” variation. Neither serum from healthy controls or from hospitalized patients contains interfering substances. Gas-Liquid Chromatography

15. Place 5 ml of serum in a glass-stoppered centrifuge tube adjust the pH to 4.0 by the dropwise addition of HC1. add 5 ml of chloroform containing 0.25 g of androsterone. The contents of the tube are next mixed and then centrifuged. Aspirate and discard the aqueous (top) layer containing serum and protein. Pipet 4.0 ml of the organic layer into another glass- stoppered tube. Evaporate the chloroform under a filtered stream of dry air. After cooling, dissolve the residue with 20 tl of chloroform. Inject 5.0 tl of the solution into the gas chromatograph for quantitation of propoxyphene. Gas-Liquid Chromatography Count.