Transcript Propoxyphene

Propoxyphene
Prepared by:
Maha Al-Mazyed
Propoxyphene
Brand names
Darvon® Compound-65
Pulvules®
Darvon-N®
E-Lor®
PC-CAP®
Wygesic®
Propoxyphene
CLASS:
• Propoxyphene is a mild narcotic analgesic
structurally related to methadone.
• The potency of propoxyphene hydrochloride is
from two-thirds to equal that of codeine.
Propoxyphene
DESCRIPTION
• Odorless
• white crystalline powder
• bitter taste
• freely soluble in water
Chemical structure:
(2S,3R)-(+)-4-(Dimethylamino)-3-methyl-1,2-diphenyl-2butanol propionate (ester) hydrochloride.
INDICATIONS
For the relief of mild to moderate pain
SIDE EFFECTS
•dizziness
•drowsiness
•upset stomach
•vomiting
•constipation
•stomach pain
•skin rash
•mood changes
•headache
•difficulty breathing
Symptoms of Overdosage:
• 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.
Treatment of Overdosage:
• 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
Drug Abuse and Dependence
• Propoxyphene, when taken in higher-thanrecommended 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.
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.
Analysis:
High-performance liquid chromatographic (HPLC):
• 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.
Gas-Liquid Chromatography
• 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 Count.
• 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 glassstoppered 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.