====== 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 =====
==== 0.1 Cholinergic Toxidrome in Organophosphate Toxicity ====

  * Also see: [[wikitox:cholinergictoxicity|Cholinergic Toxicity]], [[wiki:2.2.7.4.5_organophosphates|organophosphate toxicity]].
  * A rapid loading protocol and infusion is used.
  * **Adult:**
      * 💊 **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.
  * **Child:**
      * 💊👶 **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 (e.g. in adults HR > 80bpm, systolic BP >80 mmHg)
  * Observe for signs of over-atropinization:
      * Confusion
      * Pyrexia
      * Absent bowel sounds


==== - Cholinergic Toxidrome Excluding Organophosphate Toxicity ====
  * Also see: [[wikitox:cholinergictoxicity|cholinergic toxidrome]].
  * **Adult:** 💊 **Atropine 0.6 mg IV**, double the dose q5min until target end points for atropinization reached; max cumulative dose 3 mg.
  * **Child:** 💊👶 **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 (e.g. in adults HR > 80bpm, systolic BP >80 mmHg)
  * Observe for signs of over-atropinization:
      * Confusion
      * Pyrexia
      * Absent bowel sounds

==== - Bradycardia ====
  * Also see: [[:beta_blocker_toxicity|Beta Blocker Toxicity]].
  * **Adult:** 💊 **Atropine 0.6 mg IV**, q15min; max cumulative dose 3 mg.
  * **Child:** 💊👶 **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:**
  * Tablets: 0.4 mg.
  * Ampoules of 0.5-0.6 mg/mL or 3 mg/10mL.
  * Eye drops: atropine sulfate 1%.
  * IM autoinjector: 2mg/0.7mL.
===== - References =====

Further Reading:

~~REFNOTES~~