1) Receptor-level action → clinical effects
**Primary:**
* **μ-opioid receptor agonist (synthetic phenylpiperidine opioid)**
* **μ₁ activation:** analgesia, euphoria
* **μ₂ activation:** respiratory depression, bradycardia, constipation
* **κ-receptor agonist activity:** mild → spinal analgesia, dysphoria (sometimes undesirable)
**Other receptor / system effects:**
* **Antimuscarinic (anticholinergic) action:** from structural similarity to atropine → **tachycardia**, **dry mouth**, **blurred vision**, **less miosis**.
* **Monoamine reuptake inhibition (serotonin + noradrenaline):** → **serotonin toxicity risk** when combined with MAOIs/SSRIs.
* **No histamine release** → generally haemodynamically stable.
**Clinical effects derived from above:**
* **CNS:** analgesia, euphoria, sedation, but less potent (≈ 0.1× morphine).
* **CVS:** mild **tachycardia** from antimuscarinic effect (unlike morphine/fentanyl).
* **Respiratory:** dose-dependent depression.
* **GI:** constipation, nausea, biliary spasm (but less than morphine).
* **Seizures/tremors:** due to accumulation of **normeperidine** (active metabolite, CNS excitant).
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2) Vial strength, preparation & basic pharmacokinetics (+ disadvantages)
**Vials/amps:** 50 mg/mL (1 mL ampoules most common).
**Onset:** 5–10 min IV / 10–15 min IM **Peak:** ~20 min
**Duration:** 2–4 h (shorter than morphine)
**Distribution:** Lipid-soluble → rapid CNS penetration.
**Metabolism:** hepatic (demethylation) → **normeperidine** (active, long t½ ~15–30 h).
**Excretion:** renal (both parent + metabolite).
**Disadvantages due to PK & receptor profile:**
* **Neurotoxicity risk** from normeperidine (especially in renal failure or prolonged use).
* **Shorter duration** → frequent redosing.
* **Serotonin syndrome risk** (MAOI/SSRI interaction).
* **Antimuscarinic tachycardia** undesirable in cardiac surgery.
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3) Practical dosing
## A. Anaesthesia / Peri-operative
* **Pre-med / analgesia:** 25–100 mg IM 30–60 min pre-op.
* **Intra-op analgesia:** 25–50 mg IV slow bolus (≈ 0.5–1 mg/kg).
* **Post-op analgesia:** 25–50 mg IV/IM q3–4 h as needed (max 400 mg/24 h).
* Rarely used for cardiac surgery due to **tachycardia** and **metabolite accumulation**.
## B. ICU use
**Generally avoided** due to unpredictable kinetics and **normeperidine accumulation** → neurotoxicity, seizures, agitation.
If absolutely necessary (e.g., shivering post-op):
* **Anti-shivering dose:** 25 mg IV slow bolus (useful for post-anaesthetic shivering).
* Avoid repeated dosing or continuous infusions.
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4) Special populations — dosing cautions
### Pregnancy
* Crosses placenta; may cause neonatal respiratory depression and neurobehavioural changes.
* **Short-acting** → sometimes used in early labour, but largely replaced by safer opioids.
### Lactation
* Secreted into breast milk → potential sedation/apnoea in infant.
* Avoid repeated doses in nursing mothers.
### Hepatic impairment
* Reduced metabolism → prolonged effect, increased risk of normeperidine accumulation → **use lower dose or avoid**.
### Renal impairment
* **Major contraindication** — normeperidine accumulation → seizures, tremor, delirium.
* *Never use in chronic kidney disease or ICU renal replacement therapy patients.*
### Obesity
* Lipophilic with large Vd → prolonged half-life and delayed recovery with repeat doses.
* **Dose on Lean/Adjusted Body Weight**.
### Paediatrics
* **Analgesic dose:** 0.5–1 mg/kg IV/IM q4h (max 100 mg per dose).
* Avoid repeated doses or infusions (neurotoxic risk).
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5) Drug interactions (clinically key)
* **MAOIs / SSRIs / SNRIs / TCAs:** may precipitate **serotonin syndrome** → hyperthermia, rigidity, autonomic instability → **absolute contraindication** within 14 days of MAOI use.
* **CNS depressants (benzos, propofol, volatiles):** additive respiratory/CVS depression.
* **Anticholinergics:** enhanced tachycardia, confusion.
* **Rifampicin / enzyme inducers:** ↑ metabolism, ↓ analgesic duration.
* **Seizure-threshold-lowering drugs** (tramadol, antidepressants): ↑ seizure risk.
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6) Significant complications & management
| Complication | Mechanism / Features | Management |
| ------------------------------------------------ | ------------------------------------------------------------------------------- | --------------------------------------------------------------------------------------------------- |
| **Neurotoxicity (seizures, tremors, agitation)** | Normeperidine accumulation (esp. renal/hepatic failure, elderly, prolonged use) | Stop drug; benzodiazepine for seizure; avoid further dosing. |
| **Serotonin syndrome** | Interaction with MAOIs/SSRIs/SNRIs | Stop all serotonergic drugs; supportive care; cooling; benzodiazepine; consider **cyproheptadine**. |
| **Respiratory depression** | μ₂ activation | Airway support; **naloxone** 40–80 mcg IV q2 min; repeat/titrate as needed. |
| **Tachycardia / arrhythmia** | Antimuscarinic effect | β-blocker or reduce dose; avoid in coronary disease. |
| **Hypotension (rare)** | High doses or synergistic depressants | Fluids; vasopressor if required. |
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Pocket viva line
Pethidine (Meperidine) is a μ-opioid agonist with additional antimuscarinic and monoamine reuptake inhibition properties.
It provides short-acting analgesia but can cause tachycardia, seizures (normeperidine accumulation), and serotonin toxicity.
Avoid in renal/hepatic impairment and ICU infusions; occasionally used as 25 mg IV for post-anaesthetic shivering.
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