Question 19

Describe the pharmacology of atropine.

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College Answer

Most candidates used a good structure to compose their answer. Better candidates understood that CNS effects occur as atropine is a tertiary amine that crosses the blood brain barrier. The mechanism of action was required. Indications for use should have included bradycardia, organophosphate poisoning, drying of secretions etc. Reasonably extensive details regarding pharmacodynamics was expected, including potential toxic effects. There was limited knowledge regarding pharmacokinetics.

Discussion

Name Atropine
Class Anticholinergic
Chemistry Tropane alkaloid
Routes of administration Oral, IV, subcutaneous, inhaled, intraocular, and topical on the mucosa
Absorption Well absorbed - 90% bioavailability
Solubility pKa 9.7; the sulfate salt is reasonably water-soluble, 1g in 455ml of water
Distribution VOD=1-6L/kg; 50% protein bound
Target receptor Both agents have similar affinities for muscarinic receptors (M1-M5), which are mainly Gq-coupled receptors. Glycopyrrolate does not have a chance to bind the M1 receptors because these are mainly found in the CNS.
Metabolism 50% metabolised, mainly by hepatic enzymatic hydrolysis, into a variety of metabolities, including tropane, tropic acid, and noratropine
Elimination 50% is eliminated unchanged
Time course of action Half life is 2-5 hours, but the duration of tissue-specific efects could be longer, eg. mydriasis could last as long as 96 hours
Mechanism of action By compettively blocking the effets of acetylcholine on Gq-coupled muscrinic receptors, both agents decrease the intracellular concentration of ioniased calcium and cAMP. This results in numerous downstream clinical effects.
Clinical effects

- Decreased airway secretions
- Bronchodilation
- Tachycardia
- Urinary retention
- Decreased gastric acid secretion
- Decreased intestinal motility
- Constipation

CNS effects:

- Delirium, hallucinations
- Mydriasis

- Antiemetic effect

Single best reference for further information Shutt, 1979


 

References

Lounasmaa, Mauri, and Tarja Tamminen. "The tropane alkaloids." The alkaloids: chemistry and pharmacology 44 (1993): 1-114.

Mirakhur, R. K. "Comparative study of the effects of oral and im atropine and hyoscine in volunteers." British journal of anaesthesia 50.6 (1978): 591-598.