Cholinesterase Inhibitors. Flashcards
What are the functions of cholinesterase inhibitors?
It inhibits acetylcholinesterase.
What happens when acetylcholinesterase is inhibited?
ACH builds up in the synaptic cleft and this increases cholinergic activity.
What are the 2 categories of acetylcholinesterase inhibitors?
Reversible inhibitors.
Irreversible inhibitors.
What are some examples of reversible acetylcholinesterase inhibitors?
Physostigmine.
Pyridostigmine.
Neostigmine.
Edrophonium.
What are some examples of irreversible acetylcholinesterase inhibitors?
Organophosphate.
What are the 2 active sites on ACHE?
An anionic site.
An esteratic site.
What does the anionic site of ACHE bind to?
Positively charge molecules such as the nitrogen on ACH.
What does the esteratic site of ACHE bind to?
The carboxyl group on ACH.
How does ACHE break down ACH?
It combines with water to form acetic acid and choline.
What happens to the choline that is formed via the breakdown of ACH by ACHE?
It is recycled.
Is the ACHE enzyme re-usable?
Yes.
How do reversible cholinesterase inhibitors work?
The bind to the ionic and esteratic sites of ACHE and are then slowly broken down by ACHE.
How do organophosphate compounds inhibit ACHE?
They bind to the ionic and esteratic sites of ACHE and cannot be removed.
Organophosphate compounds are found in what substances?
Pesticides.
What are 4 examples of reversible cholinesterase inhibitors?
Physostigmine.
Neostigmine.
Pyridostigmine.
Edrophonium.
Can physostigmine act in the CNS?
Yes, as it can cross the blood brain barrier.
Is physostigmine a reversible or irreversible cholinesterase inhibitor?
A reversible cholinesterase inhibitor.
What conditions is physostigmine used to treat?
Glaucoma.
It is the antidote for atropine toxicity.
Physostigmine can be used as the antidote for what?
Atropine toxicity.
How is neostigmine absorbed?
Orally.
Does neostigmine affect the CNS?
Yes, but not as much as physostigmine.
What receptors will neostigmine bind to?
Nicotinic receptors at the neuromuscular junction.
What 2 conditions is neostigmine used to treat?
Myasthenia gravis.
Reverse neuromuscular blockade.
Is neostigmine a reversible or irreversible cholinesterase inhibitor?
A reversible cholinesterase inhibitor.
Is edrophonium a reversible or irreversible cholinesterase inhibitor?
A reversible cholinesterase inhibitor.
How does edrophonium interact with ACHE?
It binds to the ionic site and the esteratic site.
Edrophonium will compete with what to bind to ACHE?
ACH.
Does edrophonium have a short or long duration of action?
A short duration of action.
What conditions is edrophonium used for?
For diagnosis of myasthenia gravis.
Anti curare.
What is a significant side effect of edrophonium?
Bradycardia.
What is the preferred drug for treatment of myasthenia gravis?
Pyridostigmine.
What is the pharmacological effect of neostigmine on skeletal muscle?
Stimulation of nicotinic receptors.
Will neostigmine be more likely to affect skeletal muscle at high or low doses?
At low doses.
What are anticurare agents?
Antagonists to non-depolarising neuromuscular blocking agents.
What are common pharmacologic effects of reversible cholinesterase inhibitors?
Ganglionic stimulation.
Hypotension, bradycardia, arrhythmia.
Bronchoconstriction.
Contraction of the urinary bladder.
What are the side effects of large doses of physostigmine?
Stimulation and then depression of the CNS.
What are the side effects of massive doses of physostigmine?
Convulsions.
What are the 6 side effects of neostigmine?
Skeletal muscle weakness.
Nausea.
Vomiting.
Colic.
Diarrhoea.
Bradycardia.
What is the antidote for toxic effects caused by reversible cholinesterase inhibitors?
Atropine.
Will organophosphates penetrate the blood brain barrier?
Yes.
What are 3 compounds that act as irreversible cholinesterase inhibitors?
Pesticides.
Nerve gas.
Dichlorvos.
What is the mode of action of irreversible cholinesterase inhibitors?
It binds to and irreversibly inhibits ACHE.
What are the symptoms of organophosphate poisoning?
Increased salivation.
Vomiting.
Diarrhoea.
Frequent urination.
Bradycardia.
Hypotension.
Muscle twitching/paralysis.
What are the 2 antidotes for organophosphate poisoning?
Atropine as it will bind to ACHE and prevent the toxin from binding.
Pralidoxime will help re-generate ACHE enzymes that are blocked.
How does pralidoxime act as an antidote for organophosphate poisoning?
It removes the organophosphate from the ACHE.
How soon should we give pralidoxime to victims of organophosphate poisoning?
As soon as possible.
