anti-muscarinic anticholinergic agents

see also:

• pharmacology main index
• parasympathetics - the actions of muscarinic receptors

• mydriasis, cycloplegia, tachycardia, antispasmodic GIT;
• dry mouth, decr. fasting gastric acid secretion; decr. motility;
• dilates pelves, calyces, ureters, bladder;
• delayed emptying of GB after fatty meal;
• dry, hot skin;

• blurred vision; dry mouth; hyperthermia (esp. infants);
• constipation; urine retention; tachycardia (esp. fit young adults);
• precipitate glaucoma;
• NB. low dose may cause initial mild bradycardia;

• Overdoses of anticholinergics such as atropine are remarkably safe in ADULTS but DANGEROUS in CHILDREN!
  • Children much more susceptible to toxic effects esp. hyperthermia (except tachycard.);
  • Although recovery has occurred in children with 400mg, death has occurred with 2mg !!
• tachycardia with weak pulse; iris practically obliterated;
• skin flushed, hot, dry & scarlet; ataxia; restlessness; excitement;
• delirium; toxic psychoses (sometimes even from top.ophth. use!); coma;
• ie. “Dry as a bone, blind as a bat, red as a beet, mad as a hatter”

• atropine
  • belladoona (Atrop spp)
• Scopolamine (l-hyoscine):
  • henbane (Hyoscyamus spp)
  • Used IM (0.008mg/kg) with narcotic → decr. secretions;
  • may → tranquillisation & amnesia but hyperexcit. if pain;
  • Used to prevent motion sickness:
    • top.patches 1.5mg releasing 1mg over 72hrs, steady state @ 5hrs;
      • → apply 5-6 hrs before travel! only age 10-65yrs;
    • after removal, plasma [] falls over a few hours;
    • must wash hands after handling else transfer to eyes
  • may cause idiosync. confusional states/hallucination
• other plants:
  • Datura spp (Angel's trumpet)
  • Duboisia spp (Corkwood) such as D. myoporoides - used by Australian aborigines

• Homatropine hydrobromide:
  • mainly use as mydriatic: 1% → peak 40-60min; return normal 1-3 days;
    • 5% → full mydriasis but still not full cycloplegia;
• Cyclopentolate HCl:
  • mainly as mydriatic: 0.5-1% → peak 30-60min, return normal 1 day;
• Tropicamide:
  • mainly as mydriatic: 0.5-1% → peak 20-40min, return normal 6hrs;
• Dicyclomine:
  • Used in peptic disease & hypermotility states;

• Parkinsonism → decr. dopamine in striatum → inc. excitatory cholinergics there
• Benztropine (Cogentin):
  • synthetic compound result f. combination active portions of both atropine & diphenhydramine → antimusc. & antihistamine actions;
  • Often used to Rx oculogyric crises: 1-2mg IM then 1-2mg bd/tds oral;
  • NB. because it has potent atropine-like actions care in children & note that it is C/I in <3yr olds!!
• Benzhexol (Trihexyphenidyl HCl) (Artane):
  • similar activities to atropine but usually adverse effects less;
  • Most commonly used anticholinergic for Parkinson's;

• These more polar drugs have less CNS effects than atropine but in toxicity may cause significant ganglionic blockade resulting in orthostatic hypotension - this may be reversed by phenylephrine or methoxamine.
• ipratropium:
  • lacks atropine's CNS effects & rel.lack of inhib. of ciliary beating;
  • more potent bronchodilatory, dry mouth & tachycardic effects;
  • M3 receptor half life 3hrs ⇒ duration action 4-6hrs, max. response at 1.5-2hrs ⇒ qid dosing
  • when inhaled, little systemic effect as <1% absorbed from lungs/GIT;
• tiotropium bromide:
  • structural analague of ipratropium
  • M3 receptor half life 36hrs ⇒ once daily dosing
  • increases FEV1 & quality of life in pts with COPD, lengthening time to 1st exacerbation & time to 1st hospital admission
  • number pts needed to Rx for 1 yr to prevent:
    • one exacerbation = 9 pts
    • one admission = 23 pts
• propantheline:
  • Once used in Rx of PU & still in Rx of some diarrhoeal conditions;
• glycopyrrolate:
  • Once used in Rx of PU & still in Rx of some diarrhoeal conditions;
  • sometimes used as premed. for ketamine aneasthesia to reduce secretions
  • now available as long acting muscarinic antagonist inhaler (LAMA) for chronic obstructive pulmonary disease (COPD) as glycopyrronium bromide and marketed as:
    • Seebri breezhaler
    • Ultibro Breezhaler 110/50 (indacaterol + glycopyrronium) - introduced Aust. 2014
• aclidinium:
  • long acting muscarinic antagonist inhaler (LAMA) for chronic obstructive pulmonary disease (COPD) marketed as:
    • Bretais Genuair - introduced Aust. 2014
• umeclidinium:
  • long acting muscarinic antagonist inhaler (LAMA) for chronic obstructive pulmonary disease (COPD) marketed as:
    • Incruse Ellipta - introduced Aust. 2014
    • Anoro Elipta - (vilanterol + umeclidinium)

• these are used to Rx overactive bladders, urgency and urge incontinence
• they may cause urinary retention, blurred vision, dry mouth, constipation, acute glaucoma, tachycardia, prolonged QTc, and heat illness in hot weather due to reduced perspiration
• Tolterodine tartrate:
  • antimuscarinic introduced in 2005 to help Rx urinary incontinence & over-active bladder
  • acts on M2 and M3 receptors but preferentially targets bladder receptors
  • less side effects than oxybutynin (M3 and M1 selective and acts more on the parotids than the bladder)
• Darifenacin hydrobromide:
  • antimuscarinic introduced in 2007 with more affinity for M3 receptors & thus used in Rx of over-active bladder
• Solifenacin succinate:
  • antimuscarinic introduced in 2007 with more affinity for M3 receptors & thus used in Rx of over-active bladder