Oxycodone

Oxycodone (ox-i-koe’done) is a semi-synthetic opioid medication used for treating moderate to severe pain. Oxycodone has the potential to be highly addictive and is a common drug of abuse. It was first synthesized in 1917. Oxycodone is on the WHO’s List of Essential Medicines.

Prescribers need to be cognizant of local laws regarding prescribing restrictions on opioids.

Oxycodone is available by mouth or under the tongue and in slow and immediate release forms and as an injection formulation – availability of the different forms varies by country. It is also available as combinations with paracetamol/acetaminophen, ibuprofen, naloxone, naltrexone and aspirin.

Mechanism of Action:
agonistic properties on mu, kappa, and delta-type opioid receptors, with the strongest affinity being for mu-type receptors.[4] Upon binding to these G-protein coupled receptors, oxycodone stimulates the exchange of GDP on the G-alpha subunit for GTP, resulting in the inhibition of adenylate cyclase and a decrease in intracellular cAMP. This signal cascade leads to a consequent inhibition of the nociceptive neurotransmitters acetylcholine, dopamine, GABA, noradrenaline, and substance P and the hormones glucagon, insulin, somatostatin, and vasopressin. As with other opioids, oxycodone causes hyperpolarization and reduced excitability of neurons in the central nervous system (CNS). This generalized CNS depression results from the agonistic effect on kappa-type receptors, leading to N-type voltage-gated calcium channels closure. In contrast, stimulation of the mu and delta-type receptors opens calcium-dependent inward-rectifying potassium channels.[5]

Pharmacokinetics:
Pharmacokinetic data
Bioavailability By mouth: 60–87%[5][6]
Protein binding 45%[5]
Metabolism Liver: mainly CYP3A, and, to a much lesser extent, CYP2D6 (~5%);[5] 95% metabolized (i.e., 5% excreted unchanged)[8]
Metabolites • Noroxycodone (25%) [7][8]
• Noroxymorphone (15%, free and conjugated)[7][8]
• Oxymorphone (11%, conjugated)[7][8]
• Others (e.g., minor metabolites)[8]
Oxycodone is metabolized by the hepatic enzymes CYP3A4 and CYP2D6, producing the metabolites noroxycodone and oxymorphone, respectively. These metabolites get excreted from the body via the kidneys
Elimination half-life By mouth (IR): 2–3 hrs (same t1/2 for all ROAs)[8][6]
By mouth (CR): 4.5 hrs[10]
Duration of action By mouth (IR): 3–6 hrs[8]
By mouth (CR): 10–12 hrs[11]
Excretion Urine (83%)[5]

Dosage:
For acute pain: 5 to 15 mg range, every 4 to 6 hours
For chronic pain, start at 2.5 to 10 mg every 4 to 6 hours
The minimum effective plasma concentration for a clinical response can vary widely and may increase with repeated dosing due to the development of tolerance.

Contraindications:
Hypersensitivity, opiate addiction, asthma (risk of respiratory suppression), ileus

Pregnancy:
Opioids can cross the placental barrier
In Australia, Category C and Category B in the USA.
Withdrawal symptoms have been reported in newborns if the mother took Oxycodone during the pregnancy

Side effects
Common: euphoria, constipation, nausea, vomiting, loss of appetite, drowsiness, dizziness, headache, itching, dry mouth, sweating.
Severe: addiction and substance abuse, irritability, depression or mania, delirium, hallucinations, hypoventilation, gastroparesis, bradycardia, hypotension.
Withdrawal symptoms are common.

Overdose:
An overdose of oxycodone causes a shallow breathing, slowed heart rate, cold/clammy skin, pauses in breathing, hypotension and constricted pupils.
This can progress to a circulatory collapse, respiratory arrest and be fatal.
Treatment of overdose is with IV naloxone, IV fluid and vasopressors.

Interactions:
Alcohol; cimetidine (increased toxicity); CYP3A4 inhibitors (increases oxycodone levels; eg clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil and grapefruit); MAOI’s (increases toxicity)

Brand names: Endone (Aspen Pharma), Roxicodone (Xanodyne Pharmaceuticals), Oxaydo (Egalet), OxyContin (Purdue Pharma) and others
Chemical Formula: C₁₈H₂₁NO₄
Not to be confused with: hydrocodone

Advice to Patients:
Avoid grapefruit.
Dizziness and drowsiness are common. Tips to avoid postural hypotension.
There might be an impaired mental and physical ability needed for carrying out potentially hazardous tasks such as driving and operating heavy machinery.
Addiction risk and withdrawl symptoms.

In Australia, oxycodone is on the National Podiatry Scheduled Medicines List for use by authorised Podiatrists. It is only permitted to be used in the short-acting/immediate release form.

Other Opioid analgesics:

Opioid Analgesics and Antagonists:
μ-opioid receptor agonists:
Natural opium alkaloids:	Morphine	Codeine
Semisynthetic opioids:	Oxycodone	Diacetylmorphine (Heroin)	Pholcodine	Ethylmorphine
Synthetic opioids:	Pethidine	Methadone	Fentanyl	Tramadol
Complex action opioids:
Agonist-antagonists (κ-opioid receptor):	Nalorphine	Pentazocine	Butorphanol
Partial μ agonist and κ antagonist:	Buprenorphine
Pure opioid antagonists:
Naloxone	Naltrexone	Nalmefene

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