• These are also known as anti-cholinergic drugs. Ipratropium has been included here because it is a quaternary amine.
  1. The prototypical drug is atropine, a tertiary amine alkaloid ester of tropic acid.
  2. Hyoscine (scopolamine) is the l-isomer of atropine.
  3. Glycopyrrolate, ipratropium and tiotropium are quaternary amines
  4. Benztropine is a tertiary amine.
  1. These drugs work by blockade of cholinergic action at the muscarinic receptors
    • Atropine in particular does not distinguish between the M1, M2 and M3 receptors.
    • Atropine does not have nicotinic blocking actions at clinical doses.
    •  Note that salivary, bronchial and sweat glands are more susceptible to atropine than the GI glands.
  2. Organ system effects
    • CNS
      1. Scopolamine has marked central effects due to its ability to cross the BBB. It causes amnesia and drowsiness.
      2. Anti-cholinergic drugs may reduce the tremor associated with Parkinson’s disease (this is thought to be due to the fact that a reduction in dopamine will cause a relative excess of cholinergic activity)
      3. Note that motion sickness is mainly due to cholinergic transmission, and that scopolamine therefore may be helpful.
    • CVS
      1. Atropine causes tachycardia by overcoming vagal blockade
      2. However, note that a low dose of atropine may result in an initial bradycardia as well.
    • Eye
      1. Mydriasis, cycloplegia and reduced secretions
    • Other effects
      1. Blind as a bat, mad as a hatter…
    • Respiratory * (important)
      1. Overall causes bronchodilation and a reduction in bronchial secretions (however, these effects are not as significant as the effect of β-agonists)
      2. Ipratropium and tiotropium are quaternary amines used for this specific purpose. Ipratropium is a short acting drug, with onset of action 1-3 minutes after administration, peak effect of 1-2 hours and duration of action 4-6 hours. PK and PD of ipratropium is listed in the table below:
  • Inhaled/nebulized. Because ipratropium is a charged molecule, very little is absorbed systemically.
  • >90% is swallowed, only ~10% reaches the lower airways
  • >90% excreted unchanged in faeces
  • Bronchospasm/asthma/COPD
  • Hypersensitivity to atropine
Special precautions
  • Acute closed angle glaucoma
  • Urinary retention/BPH
  • Additive effect with salbutamol
  • Additive effect with other anti-cholinergics
Adverse effects
  • Very rare, due to poor absorption from the lungs. However, CNS effects include nervousness and dizziness
  • Anti-cholinergic effects (again, rare).
  1. Depending on drug, may be PO, IV or inhaled
  1. Benztropine and scopolamine will cross the BBB and have CNS effects. Atropine will cross the BBB as well, but tends to have less central effects.
  2. Glycopyrrolate, ipratropium and tiotropium are minimally absorbed.
  1. Anti-cholinergic drugs tend to have short half-lives. They are metabolized in the liver.
    • T ½ of atropine is ~ 4 hours.
    • Importantly, note that atropine should never be used for eye examination because while its effects on other organs may last only several hours, its T ½ in the eye is very long – cycloplegia and mydriasis may last for 7 days.
  1. Urine
    • Note that atropine in particular is mostly excreted unchanged in the urine (60%) and not particularly metabolized in the liver.
  1. CNS
    • Anti-Parkinson drug
    • Benztropine may be used to reverse the extra-pyramidal symptoms caused by dopaminergic blockade (e.g. metoclopramide)
  2. CVS
    • Used to reverse symptomatic bradycardia/high degree heart block
  3. Pre-anaesthesia
    • Causes bronchodilation
    • Reduces bronchial secretions and laryngospasm
  4. Toxicology
    • Used in cholinergic toxicity (organophosphates/carbamates/mushroom toxicity)
  1. Eye – acute narrow angle glaucoma
  2. GIT – ileus, known toxic megacolon or severe colitis
  3. Genitourinary (GUT) – urinary retention/BPH
  4. Myasthenia gravis
Special precautions
  1. Additive effects with TCA/anti-psychotics/anti-histaminergic/anti-Parkinsonian drugs.
Adverse events
  1. Remember the anti-cholinergic mnemonic (blind as a bad, mad as a hatter, hot as a hare, red as a beet, dry as a bone, the bladder and bowel lost its tone and the heart runs alone).
  1. 0.6mg atropine every 5 minutes.
Withdrawal syndrome
Special notes