Describe the pharmacology of atropine.
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.
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
- ConstipationCNS effects:
- Delirium, hallucinations
- Mydriasis- Antiemetic effect
Single best reference for further information Shutt, 1979
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.