TeacherOfMedicine: Acetylcholinesterase inhibitors

Acetylcholine is an important central nervous system (CNS) neurotransmitter, which is essential to many brain functions including learning and memory.
Once an action potential reaches the terminal axon of a motor neuron, acetylcholine is released from the presynapse and binds to the post-synpatic membrane to transmit signals across the synapse.
The breakdown of acetylcholine is therefore essential to end acetylcholine signalling.
A decrease in activity of the brain’s cholinergic system is seen in Alzheimer’s disease and in the dementia associated with Parkinson’s disease.
Acetylcholinesterase is an enzyme which degrades acetylcholine (ACh).
It is thought that by increasing the availability of acetylcholine for neurotransmission, they improve cognitive function and reduce the rate of cognitive decline. However, recovery of function in patients with these conditions on starting treatment is modest and not universal.

Nausea, diarrhoea and vomiting are the most common adverse effects, arising from increased cholinergic activity in the peripheral nervous system. These adverse effects may resolve over time.
Patients with asthma or chronic obstructive pulmonary disease (COPD) may experience an exacerbation of symptoms.
Less common, but serious, peripheral effects include peptic ulcers and bleeding, bradycardia and heart block.
Central cholinergic effects may induce hallucinations and altered/aggressive behaviour. These resolve with reduction of dose or discontinuation of therapy.
There is a small risk of extrapyramidal symptoms and neuroleptic malignant syndrome. These are discussed more fully in first-generation antipsychotics.

Acetylcholinesterase inhibitors should be used with caution in patients with asthma and COPD and those at risk of developing peptic ulcers.
They should be avoided in patients with heart block or sick sinus syndrome.
Rivastigmine may worsen tremor in those with Parkinson’s disease.

Concomitant therapy with non-steroidal antiinflammatory drugs (NSAIDs) and corticosteroids may increase the risk of peptic ulceration.
Use alongside antipsychotics may increase the risk of neuroleptic malignant syndrome.
Bradycardia and/or heart block may occur when prescribed alongside other rate-limiting medications (e.g. β-blockers).

Edrophonium : diagnosis of MG
Pyridostigmine : treatment of MG, reversal of NMB
Neostigmine : treatment of MG
Physostigmine (eye drops) : glaucoma treatment
Rivastigmine: palliative treatment of dementia in Alzheimer disease or Parkinson disease

TeacherOfMedicine