Anticholinesterases Flashcards
MOA of anticholinesterases
Blocks hydrolytic inactivation of ACh in synapse to enhance and prolong stimulation of cholinergic receptors
Anticholinesterase sites of action
ANS- muscarinic, nicotinic, and NMJ nicotinic receptors
CNS- cholinergic neurons (especially for cognition)
Anticholinesterases cause _____ paralysis
Flaccid
Reversible (non-covalent) anticholinesterase
Donepezil
Donepezil can/can’t cross BBB
Can
Donepezil clinical use
Treatment of Alzheimer’s
Donepezil Alzheimer’s MOA
Deficiency of cerebral ACh counteracted by central inhibition of ACh degradation
Doesn’t affect disease progression
Donepezil adverse effects
Diarrhea
N/V
Bradycardia
Prototype reversible covalent anticholinesterase
Neostigmine
Low (therapeutic) doses of neostigmine increase/decrease contractile force
Increase
High (toxic) doses of neostigmine increase/decrease contractile force
Decrease (N receptor desensitization)
Neostigmine MOA
Direct agonist at Nm receptors; induce muscle contraction without ACh release
Duration of neostigmine action
2 hours
Circulating neostigmine is cleared by ____
Butylcholinesterase
Neostigmine does/doesn’t cross the BBB
Doesn’t
Clinical uses of neostigmine
Reverses effect of competitive neuromuscular blockers (paralyzing drugs) after surgery
Myasthenia gravis
How does neostigmine help with myasthenia gravis?
Increases response of myasthenic muscle to repetitive somatic nerve impulses (auto-antibodies destroy Nm receptors)
Adverse effects of neostigmine
Excess muscarinic stimulation
Paralysis of diaphragm at toxic doses
What drug fixes excessive muscarinic stimulation?
Atropine
Physostigmine is the antidote for _____ poisoning
Atropine
Difference between physostigmine and neostigmine
Physostigmine can cross the BBB
Malathion is commonly used as an _____
Insecticide
Malathion has a very long/short duration of action
Long (>50 hours)
Malathion is a _____ that is converted to its highly toxic metabolite
Prodrug
Clinical use of malathion
Topical lotion for head lice
Diagnostic test for anticholinesterase poisoning
Decreased plasma cholinesterase (butylcholinesterase) activity
Symptoms of anticholinesterase poisoning (cholinergic crisis)
Muscarinic: sweating, salivation, mitosis, bronchospasm, involuntary urination and defecation
Nicotinic: muscle weakness
CNS: confusion, ataxia, coma, respiratory depression
Antidotes of anticholinesterase poisoning
Atropine
Pralidoxime
Proalidoxime reactivates AChE only at the ___
NMJ
