Morphine vs Oxycodone

## Overview

Morphine and oxycodone are both full mu-opioid receptor agonists used for moderate-to-severe pain. Morphine is the reference opioid analgesic; oxycodone offers slightly higher oral bioavailability and is often perceived as more reliably absorbed.

## Mechanism of Action

Both activate mu-opioid receptors (MOR), coupling to Gi/Go proteins to inhibit adenylyl cyclase, increase K+ conductance (hyperpolarization), and decrease Ca2+ conductance (reduced neurotransmitter release). Net effect: spinal and supraspinal analgesia, respiratory depression, euphoria, and GI motility inhibition.

## Pharmacokinetics

Morphine: oral bioavailability ~30–40% (significant first-pass glucuronidation), half-life ~2–4 h. Key metabolites: morphine-6-glucuronide (M6G, active, potent, accumulates in CKD), morphine-3-glucuronide (M3G, inactive, may cause neuroexcitation). Active M6G requires dose adjustment in renal impairment.

Oxycodone: oral bioavailability ~60–87%, half-life ~4–6 h, CYP3A4 → noroxycodone (less active), CYP2D6 → oxymorphone (active, but minor). Less M6G-equivalent accumulation risk in renal impairment.

## Clinical Equivalence

Standard equianalgesic conversion: oral oxycodone 10 mg ≈ oral morphine 15–20 mg. Both available in immediate-release (q4h dosing) and controlled-release formulations.

## Renal Considerations

Morphine should be avoided in severe CKD/ESRD due to M6G accumulation causing prolonged sedation and respiratory depression. Oxycodone is somewhat safer in moderate renal impairment though caution is still warranted.

## Key Takeaways

- Oxycodone: higher bioavailability, safer in CKD (less M6G equivalent)
- Morphine: reference opioid, active M6G accumulates in renal failure
- Both subject to abuse potential; equianalgesic dosing conversion needed