indication

For the treatment of diarrhoea, pulmonary oedema and for the relief of moderate to moderately severe pain.

pharmacology

Oxycodone, a semisynthetic opiate agonist derived from the opioid alkaloid, thebaine, is similar to other phenanthrene derivatives such as hydrocodone and morphine. Oxycodone is available in combination with aspirin or acetaminophen to control pain and restless leg and Tourette syndromes.

mechanism of action

Oxycodone acts as a weak agonist at mu, kappa, and delta opioid receptors within the central nervous system (CNS). Oxycodone primarily affects mu-type opioid 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 oxycodone also inhibit the release of vasopressin, somatostatin, insulin, and glucagon. Opioids close N-type voltage-operated calcium channels (kappa-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (mu and delta receptor agonist). This results in hyperpolarization and reduced neuronal excitability.

toxicity

Symptoms of overdose include respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, bradycardia, hypotension, and death.

biotransformation

Hepatic

absorption

Well absorbed with an oral bioavailability of 60% to 87%

half life

4.5 hours

route of elimination

Oxycodone and its metabolites are excreted primarily via the kidney.

drug interactions

Cimetidine: Cimetidine, a moderate CYP3A4 inhibitor, may decrease the metabolism of oxycodone. Monitor for changes in the therapeutic and adverse effects of oxycodone if cimetidine is initiated, discontinued or dose changed.

Citalopram: Increased risk of serotonin syndrome

Escitalopram: Increased risk of serotonin syndrome

Fluoxetine: Increased risk of serotonin syndrome

Fluvoxamine: Increased risk of serotonin syndrome

Paroxetine: Increased risk of serotonin syndrome

Sertraline: Increased risk of serotonin syndrome

Triprolidine: The CNS depressants, Triprolidine and Oxycodone, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.