Cholinesterase Inhibitor

Aka: Cholinesterase Inhibitor, Anticholinesterase, Acetylcholinesterase Inhibitor

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II. Indications

  1. Alzheimer's Disease
    1. Increased Cholinergic Activity by Anticholinesterases crossing the blood brain barrier may reduce Dementia related symptoms
    2. Central Cholinesterase Inhibitor examples include Aricept (Donepezil), Rivastigmine (Exelon), Galantamine (Reminyl)
  2. Glaucoma
    1. Increased Cholinergic Activity the iris sphincter Muscle (Miosis)
    2. Pupil Constriction pulls the iris away from canal of schlemm, increasing Aqueous Humor outflow (decreases Intraocular Pressure)
  3. Myasthenia Gravis
    1. Peripheral Anticholinesterases (e.g. neostigmine) prolong Acetylcholine activity at the Neuromuscular Junction
    2. Overcomes the myasthenia autoantibody binding of Neuromuscular JunctionNicotinic Receptors

III. Mechanism

  1. Acetylcholine
    1. Neurotransmitter for autonomic preganglionic Neuron Synapses (CNS to autonomic Ganglion)
      1. Acetylcholine mediates both preganglionic sympathetic and Parasympathetic Systems
    2. Acetylcholine is Neurotransmitter for parasympathetic postganglionic Neurons (autonomic Ganglion to target organ)
      1. Acts at muscarinic and nictonic Acetylcholine receptors
    3. Acetylcholine is the Neurotransmitter at the Neuromuscular Junction
      1. Muscle Contraction is triggered by release of Acetylcholine into the synaptic cleft
  2. Acetylcholinesterase
    1. Acetylcholinesterase cleaves and deactivates Acetylcholine at the synaptic cleft, leading to a short AcetylcholineHalf-Life
  3. Cholinesterase Inhibitor (Anticholinesterase)
    1. Inhibit Acetylcholinesterase activity, thereby resulting in prolonged Acetylcholine activity within the Synapse
  4. Images
    1. parasympatheticNervousSystem.jpg
    2. autonomicSynapse.png

IV. Types

  1. Carbamyl Ester Inhibitors
    1. Inhibition of Acetylcholinesterase via competitively binding the Acetylcholine site
    2. On cleaving the Carbamyl Ester link, Acetylcholinesterase is carbamylated
    3. Acetylcholinesterase is deactivated for minutes to hours until it is reactivated by decarbamylation
    4. Examples include agents used in Dementia, Myasthenia Gravis and Glaucoma
  2. Organophosphorus Inhibitors (Organophosphates)
    1. High affinity binding to the Acetylcholine site renders Acetylcholinesterase permanently inactivated
    2. Acetylcholinesterase must be regenerated over days to weeks to Restore activity at the Synapse
    3. Examples include OrganophosphatePesticides and Nerve Agents

V. Medications: Central Nervous System Agents

  1. Central Cholinesterase Inhibitor for Dementia Management
    1. Aricept (Donepezil)
    2. Rivastigmine (Exelon)
    3. Galantamine (Reminyl)
  2. Physostigmine
    1. Carbamyl Ester Inhibitor administered IM/IV for reversal of AnticholinergicOverdose

VI. Medications: Peripheral Nervous System Agents (Myasthenia Gravis)

  1. Neostigmine (Prostigmine)
  2. Pyridostigmine (Mestinon)
  3. Ambenonium (Mytelase)
    1. Prolonged activity

VII. Medications: Ocular Topical Agents (Glaucoma)

  1. See Intraocular Parasympathomimetic
  2. Demacarium (Humorsol)
  3. Echothiophate (Phosphate Iodide)

VIII. References

  1. Olson (2020) Clinical Pharm, Medmaster, Miami, p. 26-7

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