Morphine vs Hydromorphone

## Overview

Hydromorphone (Dilaudid) is a semi-synthetic opioid 5–7× more potent than morphine on a milligram basis. It offers higher water solubility (enabling smaller injection volumes) and is often chosen for subcutaneous infusion or in patients with morphine intolerance.

## Mechanism of Action

Both are full mu-opioid receptor agonists. Hydromorphone may have slightly higher intrinsic mu-receptor affinity than morphine, contributing to its greater potency.

## Pharmacokinetics

Hydromorphone: oral bioavailability ~24%, IV half-life ~2–3 h, conjugated to hydromorphone-3-glucuronide (H3G, active, may cause neuroexcitatory effects like morphine-3-glucuronide). Morphine: bioavailability 30–40%, active M6G metabolite accumulates in CKD.

## Equianalgesic Dosing

IV hydromorphone 1.5 mg ≈ IV morphine 10 mg. Oral hydromorphone 7.5 mg ≈ oral morphine 30 mg. Dosing errors with hydromorphone are clinically significant given its higher potency.

## Clinical Considerations

Hydromorphone is preferred when high-volume SC or IV morphine is needed (higher water solubility allows concentrated SC infusions). Some patients who experience morphine side effects (pruritus, nausea) tolerate hydromorphone better due to receptor selectivity differences.

## Key Takeaways

- Hydromorphone: 5–7× more potent per mg; smaller volumes for infusion
- Both accumulate toxic glucuronides in CKD; hydromorphone somewhat less so
- Dose conversion errors are common given the potency difference