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anti-muscarinic anticholinergic agents

Summary of anticholinergic effects:

  • 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;

Side effects of anticholinergics:

  • 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;

Anticholinergic toxicity

  • 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”

Alkaloid antimuscarinics:

    • 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

Tertiary amine antimuscarinics:

  • 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;

Tertiary amine antimuscarinics with CNS activity (anti-Parkinsonian):

  • 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;

Quaternary ammonium antimuscarinics (less CNS effects):

  • 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.
    • 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:
  • umeclidinium:

Anti-M3 anti-muscarinics for Mx of over-active bladders:

  • 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
anticholinergics.txt · Last modified: 2019/08/02 03:45 by

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