# 1) Receptor-level action → clinical effects
**Primary:** **μ-opioid receptor agonist** (full agonist)
* Acts on **μ₁** → analgesia, euphoria, respiratory depression
* **μ₂** → respiratory depression, constipation, bradycardia, physical dependence
* **κ-receptor:** weak agonism → some spinal analgesia, dysphoria
* **δ-receptor:** minor contribution to analgesia, tolerance
**Other sites of action:**
* **Brainstem respiratory centre:** ↓ CO₂ responsiveness → respiratory depression
* **Medullary cough centre:** suppression → antitussive
* **GI μ-receptors:** ↓ peristalsis + ↑ sphincter tone → constipation, biliary colic
* **Vagal nuclei / histamine release:** bradycardia + hypotension
* **Pupil:** parasympathetic stimulation → miosis (“pin-point pupils”)
**Clinical effects from above**
* Profound **analgesia & sedation**, **euphoria**, **respiratory depression**, **miosis**, **constipation**, **urinary retention**, **pruritus**, **nausea/vomiting** (via CTZ stimulation), **histamine-induced hypotension**, **tolerance & dependence** with chronic exposure.
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# 2) Vial strength, preparation & basic pharmacokinetics (+ disadvantages)
**Vials/amps:** 10 mg/mL (1 mL amp), occasionally 15 mg/mL or 30 mg/mL; dilute to convenient concentration for infusion (e.g. 50 mg in 50 mL = 1 mg/mL).
**PK**
* **Onset:** 2–5 min IV (peak ≈ 20 min) **Duration:** 3–4 h (analgesia)
* **Distribution:** large Vd, crosses BBB slowly (slower onset vs fentanyl)
* **Metabolism:** hepatic glucuronidation → **M3G** (inactive + neuro-excitant) & **M6G** (active, potent analgesic)
* **Elimination:** renal (major), biliary (minor) t½ ≈ 2 – 4 h (prolonged in renal failure)
**Disadvantages**
* **Slow onset/offset**, **histamine-mediated hypotension**, **accumulation** in renal failure (M6G) → delayed respiratory depression, **nausea/pruritus**, **constipation**.
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# 3) Practical dosing
## A. Anaesthesia / Peri-operative
* **Premed / analgesic supplement:** 2–5 mg IV slowly (0.05–0.1 mg/kg).
* **Induction adjunct:** 0.1–0.2 mg/kg IV (rare now; use fentanyl/remifentanil instead for cardiac cases).
* **Epidural/Intrathecal:** preservative-free morphine (0.1–0.2 mg intrathecal or 2–5 mg epidural).
## B. ICU (analgesia ± sedation)
**Indications:** long-acting analgesia in intubated or post-cardiac-surgery patients when renal function normal and haemodynamics stable.
* **Bolus:** 1–4 mg IV q5–10 min to effect.
* **Infusion:** **0.5–2 mg/h** (≈ 7–30 mcg/kg/h), titrate to comfort/vent synchrony.
* Convert to enteral/PRN once stable.
* Avoid or greatly reduce if **eGFR < 30 mL/min/1.73 m²**.
**Neuraxial post-op infusions:** 0.1–0.2 mg morphine with local anaesthetic per mL in epidural at 2–6 mL/h (per local protocol).
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# 4) Special populations — dosing cautions
### Pregnancy
* Crosses placenta → fetal/neonatal respiratory depression & withdrawal with chronic use.
* **Short-term use in labour or cardiac emergencies** acceptable under obstetric guidance.
* Avoid prolonged high-dose use before delivery.
### Lactation
* Appears in milk; after a **single low dose**, generally safe.
* **Chronic or high-dose maternal use** may sedate infant → monitor or pause breastfeeding for 24 h if multiple doses given.
### Hepatic impairment
* Metabolism slowed → longer effect; dose ↓ and interval ↑.
* In severe hepatic failure, avoid repeated high boluses.
### Renal impairment
* **Major caution.** M6G & M3G accumulate → delayed, prolonged respiratory depression or agitation/myoclonus.
* Prefer **fentanyl or remifentanil** if eGFR < 30.
* If unavoidable: halve bolus & extend interval; avoid infusion.
### Obesity
* Hydrophilic → distributes mainly in lean tissue.
* **Dose on Lean/Adjusted BW** to prevent accumulation; monitor sedation closely.
### Paediatrics
* **IV bolus:** 0.05–0.1 mg/kg q2–4 h prn.
* **IM:** 0.1–0.2 mg/kg q2–4 h prn.
* **Neonates:** start 0.025–0.05 mg/kg; immature clearance → titrate slowly.
* Avoid infusions in neonates unless strictly monitored.
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# 5) Drug interactions (clinically key)
* **CNS depressants** (opioids, benzos, propofol, volatile agents, alcohol): synergistic → respiratory depression → use lower doses & monitor capnography.
* **MAOIs / SSRIs / TCAs:** risk of serotonin toxicity (rare) → avoid concurrent MAOIs within 14 days.
* **Antihypertensives / nitrates:** additive hypotension.
* **Anticholinergics:** enhanced constipation & urinary retention.
* **Partial agonist-antagonists** (buprenorphine, nalbuphine): may antagonise morphine analgesia.
* **Cimetidine:** ↓ hepatic clearance → ↑ levels.
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# 6) Significant complications & management
| Complication | Mechanism / Notes | Management |
| ----------------------------- | --------------------------------------------------------------------------- | -------------------------------------------------------------------------------------------------------------------------------- |
| **Respiratory depression** | ↓ brainstem CO₂ sensitivity; may appear > 2 h post-dose (esp renal failure) | Airway support, naloxone (40–80 mcg IV q2 min to effect, then infusion ~ 60% of effective bolus per h); monitor for re-sedation. |
| **Hypotension / bradycardia** | Histamine release + vagal tone | Fluids, antihistamines, vasopressor if needed. |
| **Nausea / vomiting** | CTZ stimulation | Ondansetron / metoclopramide. |
| **Pruritus** | Histamine ± central effect | Antihistamines / low-dose naloxone infusion (0.25 mcg/kg/h). |
| **Constipation** | μ gut inhibition | Stool softeners / laxatives from day 1. |
| **Urinary retention** | Sphincter ↑ tone | Bladder scan + catheter if symptomatic. |
| **Dependence & withdrawal** | Chronic exposure | Taper slowly if > 5–7 days use. |
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## Pocket viva line
*Morphine is a **μ-opioid receptor agonist** providing potent analgesia and sedation but causes **respiratory depression, histamine-mediated hypotension, constipation, and metabolite accumulation** in renal failure.
IV 2–5 mg slowly or infusion 0.5–2 mg/h in ICU; avoid continuous use if eGFR < 30. Monitor for delayed respiratory depression and manage with naloxone if required.*
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