Hydromorphone
Hydromorphone
Generic Name
Hydromorphone
Mechanism
- Potent μ‑receptor agonism: 3–4 × stronger than morphine and 10–20 × stronger than codeine.
- Postsynaptic inhibition: ↓ Ca²⁺ influx → ↓ neurotransmitter release and ↓ neuronal excitability.
- Minimal receptor desensitization in short‑term use, but chronic exposure still leads to tolerance.
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Pharmacokinetics
| Parameter | Details |
| Absorption | Oral bioavailability 20–50 % (first‑pass hepatic metabolism). IV/SC bioavailability 100 %. |
| Distribution | Lipophilic; high volume of distribution (~1–2 L/kg). BBB penetration: high; CNS effects prominent. |
| Metabolism | Metabolized by UGT2B7, UGT2B15, UGT2B17 → glucuronides (inactive). <1 % excreted unchanged. |
| Elimination | Half‑life: 2.5–3 h (IV); 2–3 h (oral); prolonged in hepatic impairment. Renal clearance *Key terms:* μ‑opioid receptor, first‑pass metabolism, UGT2B7
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Indications
- Acute pain in postoperative, traumatic or oncologic settings.
- Severe pain in palliative care (short‑acting formulation).
- Counter‑algesic for patients tolerating limited morphine potency.
- For patients with opioid tolerance when dose adjustment of μ‑agonists is required.
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Contraindications
| Category | Specifics |
| Contraindicated | Hypersensitivity to hydromorphone or any excipients; acute respiratory failure; severe CNS depression. |
| Drug Interactions | MAO‑I, CYP3A4 inhibitors/inducers, alcohol, benzodiazepines → ↑ somnolence, respiratory depression. |
| Warnings |
• Respiratory depression; assess SpO₂ and RR <10–12 min⁻¹. • Tolerance & dependence; taper slowly if chronic use. • Naloxone required for overdose; rapid onset of reversal. |
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Dosing
| Formulation | Adult Initial & Maintenance Dose | Notes |
| IV/SC | 0.25 mg (IV) or 0.1–0.3 mg (SC) Q4–6 h; titrate to effect. | First‑dose in morphine‑experienced patients double. Monitor vitals for 30 min. |
| Oral | 0.5–1 mg Q4–6 h; max 10–20 mg/day depending on tolerance. | Oral tablets ≈20 % bioavailability. |
| Exalgo® (ER, oral) | 6–9 mg/day, 1 × daily; adjust every 5–7 days. | Not for acute pain. |
| Renal/hepatic impairment | Reduce dose 50 % (renal) or use IV/SC (hepatic, mild). | For CrCl < 30 ml/min → avoid long‑acting form. |
Oxymorphone is a common alternative due to intermediate potency.
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Adverse Effects
- Common: nausea, vomiting, constipation, dizziness, pruritus, xerostomia, myoclonus.
- Serious: respiratory depression, hypotension, bradycardia, hallucinations, Urgent naloxone administration in severe overdose.
> *Key terms:* respiratory depression, nausea, constipation, naloxone reversal
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Monitoring
- Respiratory: RR, SpO₂; use continuous pulse oximetry in high‑dose or at risk patients.
- Cardiovascular: BP, HR; watch for hypotension and bradycardia.
- Pain: Numeric Rating Scale or Visual Analog Scale every 30–60 min initially.
- Sedation: Ramsay or MOA score.
- Gastrointestinal: Stool frequency, bowel sounds.
- Laboratory: CBC, CMP if chronic use >2 weeks.
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Clinical Pearls
- First‑Dose Doubling: In opioid‑experienced patients, initial IV/SC dose can be doubled once; thereafter titrate every 30–60 min.
- Bridging Opioid Tolerance: Hydromorphone potency ≈10–15 × morphine → safe conversion with no over‑rescue.
- Naloxone Co‑prescription: Consider prescribing naloxone auto‑injectors for patients with high opioid exposure.
- Avoid Oral/ER at Night: Oral hydromorphone’s peak effect can cause “hang‑over” sedation; ER formulations not recommended for postoperative pain.
- Use in Renal Insufficiency: Concomitant kidney disease is primarily a marker for caution; no dedicated dose‑adjustment tables exist but use lowest effective dose.
- Sublingual Administration: Not formalised; may provide quicker onset than oral but is off‑label and can be error‑prone.
- Mental Health Considerations: Hydromorphone is preferred over fentanyl in patients with a history of suicide attempts due to simpler reversal.
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• Key Takeaway: Hydromorphone offers rapid, potent analgesia with a predictable PK profile suitable for acute and short‑term chronic pain, provided its respiratory depressant potential is carefully monitored and patient‑specific titration is practiced.