Acetylcholinesterase inhibitors pharmacology (Used in MG)

Question 1

What are the 3 classes of acetylcholinesterase inhibitors?

Answer 1

• Short-acting: Endrophonium
• Medium-acting: Neostigmine, Pyridostigmine, donepezil
• Irreversible- Malathion (organophosphates), Chemical weapons (Dyflos, Sarin, Novichok)

Question 2

What happens if there is too much acetylcholine?

Answer 2

If acetylcholinesterase is inhibited too much and the levels of acetylcholine become too high, it can cause a ‘Depolarisation block’ of the neuromuscular junction

Question 3

What are the effects at the post-ganglionic prasympsthetic synapses of acetylcholinesterase inhibitors?

Answer 3

• Pyridostigmine and organophosphates have selectivity for the post-synaptic neurones of the PNS
• The cholinesterase inhibitors are known as ‘Parasympathomimetic’, meaning they mimic what the PNS normally does- rest and digest:
  These effects:
• Cardiovascular- decrease in heart rate (bradycardia), decrease cardiac output, vasodilation = decreased blood pressure
• Smooth muscle- contraction, increase peristalsis (gut motility), bladder contraction (bladder emptying), bronchoconstricion
• eye- pupil and ciliary muscle contraction= decrease in intraocular pressure, hence have been used to treat glaucoma
• Glands- increase secretions e.g. saliva, milk, tears, digestive enzymes

Question 4

What are the advantages and disadvantages of acetylcholinesterase inhibitors crossing the blood brain barrier?

Answer 4

+ Causes increased cognition- therapeutic in Alzheimers treatment
- But- can be toxic and lead to convulsions, unconsciousness, respiratory failure