Oxycodone

[SH4:p116; PI on MIMS]

Usage

Moderate to severe pain

Structure

• Semisynthetic narcotic analgesic
• Derived from opium alkaloid thebaine
• Chemical name is 14-hydroxydihydrocodeinone

Pharmacodynamics

Potency

1 mg of oxycodone PO
= Morphine 2mg PO, or 1/3 mg IV
= Pethidine 10mg PO, or 2.5mg IV
= Codeine 7mg PO (approx)
* [PI: OxyContin]

Mechanism of action

• Agonist at MOP receptors
• Weak agonist at DOP and KOP receptors

Effects

Similar to other opioid agonists

Side effects

• High abuse potential
• Risk of tempering
  * Crushing and powdering for IV or intranasal use

Overdose

Symptoms and signs

• Respiratory depression
• Somnolence
• Eventually coma and skeletal muscle flaccidity
• Rhabdomyolysis leading to renal failure has been reported
• Pulmonary oedema

 

Pharmacokinetics

Absorption

• High oral bioavailability = up to 87% after PO
  * Morphine PO bioavailability is about 30%
• Absorption of OxyContin is biphasic
  * Initial absorption of about 40% within first hour
  * than more controlled absorption

Metabolism

• Extensively metabolised to noroxycodone
  * By CYP3A isoenzymes
• Also some metabolised to oxymorphone
  * By CYP2D6

Elimination

Both metabolites eventually undergo glucuronidation

Action profile

Endone

• Analgesic effect occurs within 10-15 minutes
• Peak action in 30-60 minutes
• Persists for 3-6 hours
  * May be shorter if tolerance
• Elimination half-life = 2-4 hours

OxyContin

Maximal plasma concentration in about 3 hours

Half-life = 6.5 hours

Pharmaceutics

Formulation

• Active
  * Oxycodone hydrochloride
• Inactive
  * Stearic acid
  * Microcrystalline cellulose
  * Anhydrous lactose

Clinical

Interactions

Can potentiate anticoagulant activity of coumarin derivatives (e.g. warfarin)

Effects of oxycodone is
* Increased by alkalising agents
* Decreased by acidifying agents

Special considerations

• Reduce doses in elderly, hepatic or renal impairments
• Females have 25% higher plasma oxycodone concentration
  * Reasons unknown
• Not recommended for children under 12 y.o.