Indirect-Acting Cholinergic Agnoists

  • React with acetylcholinesterase preventing Ach from breaking down – results in ↑ Ach 
  • May bind reversibly or irreversibly 
  • Irreversible:
     - Not used therapeutically
     - Being developed to as nerve gas to be used as weapons
     - War setting – antidote readily available 

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Indications:
  • Myasthenia gravis (autoimmune disease of progressive muscle weakness / lack of muscle control)
  • Alzheimer's (there is a progressive loss of ACh-producing neurons & their target neurons)

Contraindications:
  • Allergy 
  • Bradycardia 
  • Intestinal or urinary tract obstruction 
  • Lactation

Caution:
  • Any condition that could be exacerbated by cholinergic stimulation 
  • Asthma, CAD, PUD, arrhythmias, epilepsy, or parkinsonism

Adverse Reactions:
  • Bradycardia, Hypotension
  • Bronchoconstriction  
  • ↑ bladder tone 
  • ↑ GI secretions & activity 
  • Relaxation of GI & GU sphincters 
  • Pupil constriction (miosis)

Interactions:
  • ↑ risk GI bleed if used w/ NSAIDs 
  • ↓ anticholinesterase effects if taken w/ any cholinergic drugs because these work in opposition to each other
  • ↑ theophylline levels w/ tacrine

Kinetics:
  • Well absorbed and distributed throughout the body 
  • Metabolized in the liver and excreted in the urine

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Drugs to Treat Myesthenia gravis:

1. Neostigmine (Prostigmine) - works at neuromuscular junction


2. Pyridostigmine (Regonol, Mestinon) - longer duration than neostigmine


3. Ambenonium (Mytelase) - only PO; cannot be used if patient is unable to swallow


4. Edrophonium (Tensilon, Enlon) - diagnostic agent for myasthenia gravis

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Drugs to Treat Alzheimer's:

1. Tacrine (Cognex) - 1st drug out there to treat Alzheimer's


2. Galantamine (Reminyl) - used to stop Alzheimer's progression


3. Rivastigmine (Exelon) - available in solution for swallowing ease


4. Donepezil (Atricept) - once-a-day dosing!

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Nursing Mgmt
  • if IV administer slowly 
  • Atropine sulfate on-hand in case of crisis (antidote
  • Observe for excessive salivation, diarrhea, emesis, excessive urination 
  • should be taken w/ meals 
  • Prevent injury 
  • Teaching

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Nerve Gas – Irreversible Indirect Cholinergic Agonist:

  • Irreversible acetylcholinesterase inhibitor 
  • Leads to toxic accumulation of ACh at cholinergic receptor sites


Antidotes:
Pralidoxime (Protopam Chloride); works in PNS 
  • IM or IV
  • frees up acetylcholinesterase to start breaking down ACh
  • on-hand for MG receiving an IDCA
  • antidote for irreversible acetylcholinesterase-inhibiting drugs, or nerve gas
  • Organophosphate pesticide poisoning

Atropine; works in CNS
  • Block cholinergic activity & active Ach in CNS
  • Activate Acetylcholinesterase to breakdown Ach

Adverse Effects
  • Blurred vision, dizziness, diplopia, headache, hyperventilation
  • Can cause parasympathetic crisis and muscle paralysis






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