Cholinesterase Inhibitors Flashcards
Cholinesterase inhibitors (CI) effects
skeletal muscles, brain, and autonomic system
CI enhance acton of Ach at
muscarinic and nicotinic receptors
What are the two binding sites of Cholinesterase
anionic (binding) and esteratic (hydrolysis)
Anionic site of acetylcholine esterase
formed by ring system of Trp and Phe, which bind Ach
Esteratic site of acetylcholine esterase
formed by Ser, His, and Glu, which hydrolyses
Affects of neostigmine on esterase
neostigmine is hydrolyzed by esterase but the carabamate portion remains on the Ser to block further hydrolysis for a few hours
Edrophonium
simple quaternary alcohol
binds to anionic site and prevents interaction with Ach
duration: few minutes
How do organophosphates effect Achase
Bind to esteratic site of Achase, which results in increase of cholinesterase synthesis
medical use of cholinesterase inhibitors
Alzheimers
Increase GI activity post op
Myasthenia gravis
What is Alzheimer’s
most common cause of dementia old age
improper processing beta amyloid protein
loss of cholinergic neurons in brain
Tx: Donepezil
What do you use to increase GI activity post op
neostigmine
What is myasthenia gravis
disease characterized by skeletal muscle weakness
autoimmune loss of receptors (loss of 2/3 receptors results in symptoms)
Neostigmine is effective
More common in women (3:2)
Drugs used in Myasthenia gravis
edrophonium for diagnosis
pyridostigmine orally for treatment
myasthenia crisis (low Ach) gets better with edrophonium cholinergic crisis (high Ach) gets worse with edrophonium
Catatonic (act on anionic site) Cholinesterase inhibitors
edrophonium
donepezil
Carbamate esters cholinesterase inhibitors
rivastigmine
physostigmine
neostigmine
pyridostigmine
Irreversible cholinesterase inhibitors
insecticides (organophosphates)
Non-medical cholinesterase inhibitors
Insecticides: chlorpyrifos and malathion
Nerve gases: soman
Toxicology of cholinesterase inhibitors
death due to asphyxia: bronchoconstriction, increased secretions, skeletal muscle paralysis, CNS depression
What does DUMBELS stand for
Diarrhea Urination Muscle weakness, miosis Bronchoconstriction Excitation Lacrimation Seizures, sweat, salivation
Treatment for intoxication by Achesterase inhibitors
atropine (no effect on skeletal muscle paralysis)
pralidoxime (no effect on CNS depression)
Initiate therapy quickly
Malathion is specific for
insects and head lice (pediculosis capitis)
