Question 14

College Answer

Many candidates who scored poorly confused anticholinesterase drugs with anticholinergic drugs. Some described pharmacokinetics when it was not asked. Similarly, treatment of organophosphate poisoning and/or cholinergic crisis was not asked for in the question.

Discussion

Those who were unaffected by the marking of this exam will probably agree that society would expect CICM to delay the progression of any trainee who routinely confuses acetylcholinesterase inhibitors with anticholinergic agents, but on the other hand this is a fair mistake to make in a high-stakes exam.

How would you classify these drugs? For 30% of the mark, this would have to have been something more than just the old "reversible/irreversible" distinction. What follows is a homecooked classification system which may not be consistent with the marking criteria:

• Reversible 
  • CNS pentrating:
    • ​​​​​​​Physostigmine
    • Rivastigmine
    • Donepezil
  • Peripherally acting: 
    • ​​​​​​​Neostigmine
    • Pyridostigmine
    • Edrophonium
• Irreversible 
  • ​​​​​​​Organophosphates: chlorpyrifos, malathion, tabun, sarin
  • Carbamates: oxamyl, methomyl, pirimicarb, propoxur, and trimethacarb.

Pharmacodynamics, for 70%, would also have to be more than just "increase the concentration of acetycholine in the synapse by inhibiting acetylcholinesterase". But how much more? Fortunately, this question is a repeat of Question 21 from the first paper of 2015, and the examiners back in 2015 had written a more extensive note. We know that they wanted "a catalogue of the various clinical 
uses of this class of drugs" and "a description of  the effects of these drugs on the CVS, GIT, Salivary glands, eye, NMJ and the lungs".  Thus:

• Indications for acetylcholinesterase inhibitors:
  • ​​​​​​​CNS
    • ​​​​​​​Reversal of anticholinergic agent toxicity (eg. delirium)
    • Management of dementia
    • Management of Parkinson disease
  • Peripheral
    • ​​​​​​​Reversal of nondepolarising NMJ blockade
    • Myasthenia gravis (diagnosis, eg. with edrophonium, as well as management long term)
    • Severe refractory ileus, as a prokinetic
• Clinical effects of acetylcholinesterase inhibitors:
  • Nicotinic ganglionic effects, which mostly manifest as sympathetic:
    • Hypertension
    • Mydriasis
    • Sweating
    • Tachycardia
  • CNS effects
    • Agitation or depression
    • Decreased level of consciousness
    • Coma
    • Seizures
  • Neuromuscular effects
    • Depolarising blockade; muscle paralysis
  • Other autonomic effects
    • ​​​​​​​Diarrhoea
    • Urination (i.e. increased bladder tone, reduced bladder sphincter tone)
    • Miosis
    • Bradycardia (if no ganglionic effect)
    • Bronchospasm
    • Bronchorroea
    • Emesis
    • Lacrimation
    • Lethargy
    • Salivation

Wehrwein, Erica A., Hakan S. Orer, and Susan M. Barman. "Overview of the anatomy, physiology, and pharmacology of the autonomic nervous system." regulation 37.69 (2016): 125.

Patel, Neesirg M., and Nakeya Dewaswala. "Parasympathomimetic medications." (2020).

Pappano, Achilles J. "SPECTRUM OF ACTION OF CHOLINOMIMETIC DRUGS." Basic & Clinical Pharmacology (2004): 94.

Blount, Philip J., Conner D. Nguyen, and James T. McDeavitt. "Clinical use of cholinomimetic agents: a review." The Journal of head trauma rehabilitation 17.4 (2002): 314-321.

Ebert, Thomas J. "Autonomic nervous system pharmacology." Pharmacology and Physiology for Anesthesia, Saunders, Philadelphia (2013): 218-234.