Acetylcholinesterase inhibitors (AChEI) bind to acetylcholinesterase (Achase) so it will prevent the enzyme from breaking down ACh. This will cause relatively more ACh to go in the muscarinic receptor.
Very Important Question: If parasympathomimetics mimic the stimulation of the muscarinic receptor, and AChEI’s bind up Achase, allowing more acetylcholine to stimulate the muscarinic receptor, then do AChEI’s have the same pharmacology as parasympathomimetics?
The answer is YES because they both cause the stimulation of the muscarinic receptor. The mechanism of action is just different.
Effects of AChEI’s (aka Anti-cholinesterase)
(hint, they are the same as parasympathomimetics)
So what will the AChEI’s do to the eye? Miosis, tearing, decrease intra-ocular pressure, and accommodate for near-vision.
What about to the GI tract? Increased saliva, stomach acid, and peristalsis (increase GI motility but bad for peptic ulcers).
What else? Decrease heart rate (bad for cardiac insufficiency), constrict bronchioles (bad for asthmatics), sphincter relaxation and bladder contraction (help with urination).
List of Acetylcholinesterase Inhibitors
AChEI’s are also known as anticholinesterase agents. We have many subtypes.
Short acting, reversible agent
It’s reversible meaning the drug binds to the acetylcholinesterase and eventually lets go of the enzyme.
Edrophonium (Tensilon) – Short acting. It binds to the enzyme really quickly. It’s reversible and it releases it for just a matter of minutes. This particular drug is used for diagnostic purposes: To diagnose myasthenia gravis. The theory of this myasthenia gravis is that the body isn’t producing enough ACh and that’s the cause of decrease in endurance. We can’t give a person ACh so what little bit is left is not destroyed. We use this to see if their muscle strength and endurance increases. Within a matter of minutes the effect is gone. If, as a doctor, your diagnosis is wrong and you prescribe a long-acting drug, they are going to feel terrible for 6 hours instead of 20 minutes.
Intermediate acting reversible agents
Neostigmine (Prostigmin) and Pyridostigmine (Mestinon) – These are your treatments for myasthenia gravis after you’ve made the diagnosis using edrophonium.
Physostigmine (Eserine) – Treats glaucoma by lowering the intra-ocular pressure.
The three drugs below are for Alzheimer’s disease. One of the theories of Alzheimer’s disease is the lack of production of ACh (like myasthenia gravis). So we use drugs that block the destruction of ACh. At best they buy us 1-2 years and they progress again.
- Donepezil (Aricept)
- Galantamine (Reminyl)
- Rivastigmine (Exelon)
Long acting IRREVERSIBLE agent:
Echothiophate and isofluorphate: These are not safe drugs. They are very dangerous drugs. These agents never let go of acetylcholinesterase. The only thing the body can do is to produce more of the enzyme. These drugs are intended only for severe cases of glaucoma. They are only used as eye drops and you have to put pressure on the corner of the eye because there is no excuse for this to get into the blood.
They are also called organophosphates. If you know about history and ecology: There was a product called DEET, these were organophosphates used to kill pests. Like all anticholinesterases, it would bind up the AChase so it wouldn’t work and the constant ACh would cause a spastic paralysis of the insect. This is how nerve gas poisons work as well. The problem is that DEET went up the food chain and affected us.