Question 21

Describe the pharmacodynamic effects and indications for the use of anticholinesterase drugs.

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College Answer

It was expected the answer would provide a structured approach to describing the 
pharmacodynamics (what the drug does to the body) of this discreet class of drugs. A brief 
acknowledgement of the drugs in this class followed by a catalogue of the various clinical 
uses of this class of drugs would be a good start. If this was followed up with a description of 
the effects of these drugs on the CVS, GIT, Salivary glands, eye, NMJ and the lungs a good 
mark would have been awarded.
A number of candidates described the actions at the receptors in detail which did not attract 
marks. The extensive range of clinical uses for this class of drugs was poorly appreciated.
Few answers demonstrated any understanding of the PD effects of the drug class. There was 
generally a good knowledge of representative drugs within this class. Failing to achieve a 
pass mark reflected scant/brief answers that just did not cover enough of the expected 
material.

Discussion

  • Acetylcholinesterase inhibitors Increase the concentration of acetylcholine in the synapse by inhibiting  its catabolism by acetylcholinesterase
  • This can be reversible or irreversible
  • The effect can include
    • Neuromuscular block (acetylcholinesterase in the neuromuscular junction) 
    • Ganglionic agonist effect (nicotinic receptors at the autonomic ganglia)
    • Muscarinic agonist effect (muscarinic receptors in the CNS and distal sites innervated by the parasympathetic nervous system)
  • 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
    • 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
  • 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

References

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.