Amiodarone is a **multi-class anti-arrhythmic** (mainly **Class III**) blocking K⁺, Na⁺, β, and Ca²⁺ channels.
It **prolongs repolarisation**, slows AV conduction, and treats both **atrial and ventricular arrhythmias** with low torsades risk.
IV: **150 mg over 10 min**, then **1 mg/min × 6 h**, then **0.5 mg/min**; oral maintenance **100–200 mg/day**.
Toxicities: thyroid, pulmonary, hepatic, ocular, neurologic.
Monitor LFTs, TFTs, ECG, CXR periodically.
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# 1) Receptor-level action → clinical effects
**Class:** *Class III anti-arrhythmic (broad-spectrum)*
**Receptor / channel effects (multi-class):**
| Mechanism | Target | Effect | Vaughan-Williams class |
| ------------------------- | --------------------------------------- | -------------------------------------------------------------- | ---------------------- |
| **K⁺-channel blockade** | Delayed rectifier K⁺ current | ↑ repolarisation time, ↑ refractory period → prevents re-entry | **III** |
| **Na⁺-channel blockade** | Fast inward Na⁺ current (use-dependent) | ↓ conduction velocity | **I** |
| **β-blockade** | β₁, β₂ antagonism | ↓ HR, ↓ AV nodal conduction | **II** |
| **Ca²⁺-channel blockade** | L-type channels | ↓ AV nodal conduction, negative inotropy | **IV** |
**Net electrophysiologic effects**
* **Prolonged action potential duration** (QT↑ but *low torsades risk*).
* **Slows SA and AV node conduction**, suppresses ectopic foci.
* **Stabilises re-entry and automatic tachyarrhythmias** in atrial and ventricular tissue.
**Clinical outcomes**
* Broad anti-arrhythmic: effective for **AF**, **atrial flutter**, **SVT**, **VT**, **VF** (esp. refractory or post-CPB).
* **Haemodynamic profile:** mild vasodilation, negative inotropy minimal (better tolerated in LV dysfunction).
* **Heart-rate control** + rhythm conversion capabilities.
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# 2) Vial strength, preparation & basic pharmacokinetics (+ disadvantages)
**IV formulation:** 150 mg/3 mL (50 mg/mL) in polysorbate solvent (non-PVC set required).
**Oral tablets:** 100 mg, 200 mg.
**Pharmacokinetics**
* **Onset (IV):** 2–5 min for rate control; 1–2 h for rhythm conversion.
* **Half-life:** biphasic — early 3–10 h; terminal **weeks (20–100 days)** → extensive tissue accumulation.
* **Metabolism:** hepatic via **CYP3A4 → desethyl-amiodarone (active)**.
* **Excretion:** biliary; negligible renal elimination.
* **Highly lipophilic** → large Vd; slow clearance.
**Disadvantages**
* **Very long half-life** → delayed toxicity reversal.
* **Multiple organ toxicities** with chronic use.
* **Hypotension and bradycardia** with rapid IV loading (solvent & vasodilation).
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# 3) Practical dosing
## A. Anaesthesia / Cardiac theatre
**Indications:** peri-operative **AF**, **VT**, **VF**, **post-CPB arrhythmia prophylaxis**.
* **IV loading:** 150 mg over **10 min** (dilute in 100 mL 5% Dextrose).
* **Then infusion:**
* **1 mg/min (60 mg/h)** for 6 h → then **0.5 mg/min (30 mg/h)** for 18 h or until rhythm stabilises (total 900–1200 mg/24 h).
* **Refractory VT/VF (ACLS):**
* **300 mg IV push** (undiluted) → may repeat **150 mg** once after 3–5 min if VF/pulseless VT persists.
* **Post-bypass prophylaxis:** 150 mg slow bolus at re-perfusion ± infusion 0.5–1 mg/min for 6–12 h.
## B. ICU / Ward maintenance
* **Oral loading:** 200 mg TDS for 1 week → 200 mg BD for 1 week → 100–200 mg daily maintenance.
* **Transition from IV to PO** once stable rhythm achieved.
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# 4) Special populations — dosing cautions
### Pregnancy
* Crosses placenta → risk of **fetal hypothyroidism, bradycardia**. Use only if life-threatening arrhythmia.
### Lactation
* Excreted in milk → avoid breastfeeding while on therapy.
### Hepatic impairment
* **Reduce dose / monitor LFTs**; hepatotoxicity possible with accumulation.
### Renal impairment
* *No dose adjustment* — not renally cleared.
### Obesity
* Highly lipophilic → large Vd, prolonged accumulation; avoid excessive long-term loading.
### Paediatrics
* **Loading:** 5 mg/kg over 20–60 min (max 300 mg), repeat q8 h PRN (max 15 mg/kg/day).
* **Infusion:** 10–15 mcg/kg/min for maintenance.
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# 5) Drug interactions (clinically key)
* **Warfarin:** inhibits metabolism → ↑ INR → halve warfarin dose, monitor closely.
* **Digoxin:** doubles serum digoxin → halve digoxin dose, monitor ECG/K⁺.
* **Statins (simvastatin, atorvastatin):** ↑ myopathy risk → use lower dose/rosuvastatin preferred.
* **β-blockers / CCBs:** additive bradycardia, AV block, hypotension.
* **QT-prolonging drugs** (fluoroquinolones, macrolides, azoles, antipsychotics): additive torsades risk (though amiodarone’s torsades risk is low).
* **CYP3A4 inhibitors (azoles, macrolides, protease inhibitors, grapefruit):** ↑ toxicity.
* **CYP inducers (phenytoin, rifampicin):** ↓ efficacy.
* **Anaesthetic volatile agents:** additive bradycardia, hypotension.
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# 6) Significant complications & management
| System | Complication / mechanism | Monitoring / Management |
| ---------------- | ----------------------------------------------------------------------------------------------- | ---------------------------------------------------------------------------------- |
| **Cardiac** | Bradycardia, AV block, hypotension (IV solvent) | Slow/stop infusion; **atropine**, **isoprenaline**, temporary pacing if needed. |
| **Pulmonary** | Interstitial pneumonitis / fibrosis (dose-related, chronic) | Baseline + periodic CXR & PFTs; stop drug; corticosteroids if severe. |
| **Thyroid** | Contains iodine → **hypothyroidism** (inhibition of T₄→T₃) or **hyperthyroidism** (Jod-Basedow) | Monitor **TFTs q6 months**; treat accordingly (thyroxine / carbimazole ± steroid). |
| **Hepatic** | Hepatitis, ↑ LFTs | Baseline + periodic **LFTs**; stop if >3× ULN. |
| **Ocular** | Corneal microdeposits (benign) / optic neuritis (rare) | Annual eye exam; discontinue if visual loss. |
| **Dermatologic** | Blue-grey skin discolouration, photosensitivity | Sun protection; usually cosmetic. |
| **Neurologic** | Tremor, ataxia, peripheral neuropathy | Dose reduction or cessation. |
| **Electrolyte** | Hypo-/hyper-thyroid effects alter cardiac response | Monitor K⁺, Mg²⁺, TFTs. |
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