====== Atropine (treatment) ======

===== - Overview =====

Atropine is an anticholinergic agent which acts as a competitive antagonist at autonomic postganglionic muscarinic receptors. It is used to treat organophosphate and carbamate toxicity, symptomatic bradycardia (e.g. in β-blocker toxicity), and chemical weapons nerve agent toxicity.

===== - Toxicologic indications & dosing =====

==== - Adult ====

** [[Cholinergic toxidrome]] in [[organophosphate toxicity]] **
  * A rapid loading protocol and infusion is used.
  * 💊 **Atropine 1.2 mg IV**, double the dose q5min until target end points for atropinization reached, then start infusion; very high doses (up to 100 mg) may be required.
  * 💊 **Atropine 10-20% of total loading dose per hour IV infusion**, usually 0.5-5 mg/hr.
  * Titrate to atropinization target end points:
    * Clear chest, no auscultatory wheeze
    * HR > 80 bpm
    * Systolic BP > 80 mmHg
  * Observe for signs of over-atropinization:
    * Confusion
    * Pyrexia
    * Absent bowel sounds


** [[Cholinergic toxidrome]] __excluding__ organophosphate toxicity **
  * 💊 **Atropine 0.6 mg IV**, double the dose q5min until target end points for atropinization reached; max cumulative dose 3 mg.
  * Titrate to atropinization target end points:
    * Clear chest, no auscultatory wheeze
    * HR > 80 bpm
    * Systolic BP > 80 mmHg
  * Observe for signs of over-atropinization:
    * Confusion
    * Pyrexia
    * Absent bowel sounds


** Bradycardia ** (e.g. [[beta_blocker_toxicity|Beta Blocker Toxicity]])

  * 💊 **Atropine 0.6 mg IV**, q15min; max cumulative dose 3 mg.


==== - Pediatric ====

** [[Cholinergic toxidrome]] in [[organophosphate toxicity]] **
  * A rapid loading protocol and infusion is used.
  * 💊👶 **Atropine 0.05 mg/kg (up to 1.2 mg) IV**, double the dose q5min until target end points for atropinization reached, then start infusion; very high doses may be required.
  * 💊👶 **Atropine 10-20% of total loading dose per hour IV infusion**.
  * Titrate to atropinization target end points:
    * Clear chest, no auscultatory wheeze
    * Resolution of symptomatic bradycardia
  * Observe for signs of over-atropinization:
    * Confusion
    * Pyrexia
    * Absent bowel sounds


** [[Cholinergic toxidrome]] __excluding__ organophosphate toxicity **
  * 💊👶 **Atropine 0.02 mg/kg (up to 0.6 mg) IV**, double the dose q5min until target end points for atropinization reached; max cumulative dose 3 mg.
  * Titrate to atropinization target end points:
    * Clear chest, no auscultatory wheeze
    * Resolution of symptomatic bradycardia
  * Observe for signs of over-atropinization:
    * Confusion
    * Pyrexia
    * Absent bowel sounds


** Bradycardia ** (e.g. [[beta_blocker_toxicity|Beta Blocker Toxicity]])
  * 💊👶 **Atropine 0.02 mg/kg (up to 0.6 mg) IV**; max cumulative dose 3 mg.


===== - Cautions & contraindications =====

===== - Special populations =====

**Pregnancy rating:** A (AU/NZ)

**Lactation:** Small amounts excreted in breast milk
===== - Adverse effects =====

  * **CV:** Paradoxical bradycardia (with low doses or given slowly), tachyarrhythmia
  * **CNS:** Delirium, coma, blurred vision
  * **Skin:** Flushing
  * **GI:** Nausea, vomiting, constipation, xerostomia
  * **GU:** Urinary retention
===== - Pharmacology =====

==== - Pharmacodynamics ====

**Mechanism of action:**
Atropine is a competitive antagonist at autonomic postganglionic muscarinic receptors. Its clinical effects manifest primarily with ↑ heart rate, ↓ secretions, bronchodilation, and mydriasis.

==== - Pharmacokinetics ====

**Absorption:**

  * Oral bioavailability: variably reported between 50-95%
  * GI tract absorption: From small intestine
  * IM bioavailability: 50%
  * Tmax:
    * IV: Almost immediate
    * Oral: 60 mins
    * IM: 11-30 mins
    * SC: 34 ± 23 mins
    * Inhaled: 15-114 mins


**Distribution:**

  * Vd: 2-4 L/kg (large Vd; widely distributed in the body)
  * Distribution t½ after IV: 1 min; rapid decline in serum concentration within first 10 mins
  * Lipid solubility:
    * Crosses blood brain barrier
    * Crosses placenta
    * Excreted in breast milk in small amounts
  * Protein binding: 14-22%

**Metabolism:** Hepatic metabolism - hepatic enzyme hydrolysis.
  * Stereoselective metabolism: biologically active L-enantiomer metabolized, biologically inactive D-enantiomer excreted unchanged in urine.
  * Metabolites: Tropine, noratropine, atropine-N-oxide, tropic acid.

**Excretion:** 

  * Elimination occurs in two phases: rapid phase t½ = 4 hrs; slow phase t½ = 13 hrs
  * Hepatic clearance: 519 ± 147 mL/min
  * Renal clearance: 90% excreted in urine over 24 hours. 30-50% as unchanged drug.

==== - Pharmaceutics ====

**Formulation:**

===== - References =====

Useful general references:

~~REFNOTES~~