====== Hydromorphone (Dilaudid®) ======

<WRAP right 340px>
<WRAP infobox>
^ Hydromorphone | {{ :neuro:opioids:hydromorphone_skeletal.svg?200 |}} |
| Brand Names | Dilaudid®, Exalgo® |
| Drug Class | [[neuro:opioids:start|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 |
</WRAP>
</WRAP>

===== 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.

<WRAP clear></WRAP>

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===== 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  

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===== Indications =====

  * Severe acute pain  
  * Chronic severe pain  
  * Cancer-related pain  
  * Postoperative pain  
  * Palliative care  

Extended-release formulation:
  * For opioid-tolerant patients only  

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<WRAP contra>
===== Contraindications =====

Absolute:
  * Significant respiratory depression  
  * Acute severe bronchial asthma  
  * Paralytic ileus  

Relative / Caution:
  * Hepatic impairment  
  * Renal impairment  
  * Elderly  
  * Concomitant CNS depressants  
  * Obstructive sleep apnea  

</WRAP>

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<WRAP details>
===== 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:
  * [[neuro:opioids:equianalgesic_dosing|Equianalgesic Dosing Guide]]

</WRAP>

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<WRAP details>
===== 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.

</WRAP>

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<WRAP details>
===== 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.

</WRAP>

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<WRAP details>
===== Drug Interactions =====

CNS depressants:
  * Benzodiazepines  
  * Alcohol  
  * Other opioids  

Additive respiratory depression risk.

</WRAP>

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<WRAP monitoring>
===== Monitoring =====

Clinical:
  * Pain control  
  * Sedation level  
  * Respiratory rate  

High-risk patients:
  * Renal function  
  * Hepatic function  

</WRAP>

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<WRAP pearls>
===== 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.  

</WRAP>

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===== Toxicity =====

Classic opioid toxidrome:
  * CNS depression  
  * Respiratory depression  
  * Miosis  

Treatment:
  * [[neuro:opioids:naloxone|Naloxone]]

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===== Comparison Within Class =====

Compared to [[neuro:opioids:morphine|Morphine]]:
  * More potent  
  * Less histamine release  
  * Less hypotension  

Compared to [[neuro:opioids:fentanyl|Fentanyl]]:
  * Less potent  
  * Less lipophilic  

Compared to [[neuro:opioids:oxycodone|Oxycodone]]:
  * More potent  
  * More commonly used IV  

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===== Related =====

  * [[neuro:opioids:start|Opioids]]
  * [[neuro:opioids:morphine|Morphine]]
  * [[neuro:opioids:fentanyl|Fentanyl]]
  * [[neuro:opioids:oxycodone|Oxycodone]]
  * [[neuro:opioids:naloxone|Naloxone]]