Hydromorphone (Dilaudid®)
| Hydromorphone |  |
|---|---|
| Brand Names | Dilaudid®, Exalgo® |
| Drug Class | Opioid (Full μ-agonist) |
| Primary Indication | Moderate–Severe Pain |
| Relative Potency | 4–7× Morphine |
| Histamine Release | Minimal |
| Respiratory Depression | Yes (dose-dependent) |
| Weight Effect | Neutral |
| Elimination | Hepatic metabolism |
| Controlled Substance | Schedule II |
| FDA Approval | 1926 |
Overview
Hydromorphone is a semi-synthetic, full μ-opioid receptor agonist used for moderate to severe pain.
It is significantly more potent than morphine and causes less histamine release, making it better tolerated in patients prone to hypotension or pruritus.
Hydromorphone is commonly used in inpatient settings and palliative care due to its potency and predictable pharmacokinetics.
Mechanism of Action
Receptor Activity
- Full μ-opioid receptor agonist
- Gi-protein coupled receptor activation
Cellular Effects
- ↓ cAMP production
- ↑ Potassium efflux → neuronal hyperpolarization
- ↓ Calcium influx → ↓ substance P & glutamate release
Net Effect
- Potent analgesia
- CNS and respiratory depression
Indications
- Severe acute pain
- Chronic severe pain
- Cancer-related pain
- Postoperative pain
- Palliative care
Extended-release formulation:
- For opioid-tolerant patients only
Contraindications
Absolute:
- Significant respiratory depression
- Acute severe bronchial asthma
- Paralytic ileus
Relative / Caution:
- Hepatic impairment
- Renal impairment
- Elderly
- Concomitant CNS depressants
- Obstructive sleep apnea
Dosing
Immediate-Release (oral):
- 2–4 mg every 4–6 hours
IV:
- 0.2–1 mg every 2–3 hours as needed
Extended-Release:
- Once daily (opioid-tolerant patients only)
Equianalgesic:
- 1.5 mg IV hydromorphone ≈ 10 mg IV morphine
- 7.5 mg oral hydromorphone ≈ 30 mg oral morphine
See:
Pharmacokinetics
Absorption:
- Oral and IV
Bioavailability:
- ~50%
Metabolism:
- Hepatic glucuronidation
- Hydromorphone-3-glucuronide (inactive but may accumulate)
Half-life:
- ~2–3 hours (IR)
Elimination:
- Renal excretion of metabolites
Less accumulation risk than morphine, but caution in severe renal impairment.
Adverse Effects
Common:
- Sedation
- Constipation
- Nausea / vomiting
- Dizziness
Serious:
- Respiratory depression
- Physical dependence
- Opioid use disorder
Less histamine release than morphine → less pruritus and hypotension.
Drug Interactions
CNS depressants:
- Benzodiazepines
- Alcohol
- Other opioids
Additive respiratory depression risk.
Monitoring
Clinical:
- Pain control
- Sedation level
- Respiratory rate
High-risk patients:
- Renal function
- Hepatic function
Clinical Pearls
- 4–7× more potent than morphine.
- Less histamine release → less hypotension.
- Commonly used in hospital and palliative settings.
- No ceiling effect (full μ agonist).
- Requires careful dose conversion from morphine.
Toxicity
Comparison Within Class
Compared to Morphine:
- More potent
- Less histamine release
- Less hypotension
Compared to Fentanyl:
- Less potent
- Less lipophilic
Compared to Oxycodone:
- More potent
- More commonly used IV