Cholinergic Drugs

Question 1

botulinum toxin

Answer 1

• function
  
  • prevents release of ACh
• moa
  
  • inhibits release of ACh by degrading synaptobrevin (SNARE) which prevents vesicle fusion/exocytosis
• clinical use:
  
  • treat focal dystonias (paralyze select muscle groups with excessive tone)
  • unmasking subclinical Lambert-Eaton syndrome
  • treats hyperhidrosis
• side effects
  
  • botulism = respiratory paralysis/death

Question 2

name the reversible anticholinesterases and their MOA

Answer 2

• neostigmine
  
  • less lipid soluble than physostigmine; does not cross BBB
• physostigmine
  
  • highly lipid solube; crosses BBB
• pyridostigmine
  
  • similar to neostigmine but longer half life
• edrophonium
  
  • very short half-life compared to others

Question 3

name the MOA of reversible anticholinesterases

Answer 3

• moa
  
  • anticholinesterase drugs bind to the cholinesterase (both acetylChE and pseudoChE) and prevent the enzyme from degrading
  • contractions get weaker until flaccid paralysis occurs; occurs because VG Na unable to return to resting state (depolarization blockade)
  • only affects nicotinic receptors

Question 4

name the clinical uses of reversible anticholinesterases

Answer 4

• increase parasympathetic tone (parasympathomimetric)
  
  • decrease intraocular pressure (glaucoma) by increasing outflow of aqueous humor
  • increase smooth muscle motiliy of GI tract
  • reversal of anticholinergic poisoning (ex: atropine)
• increase central cholinergic neurotransmission in dementia
• reversal of paralysis from non-depolarizing neuromuscular blockers

Question 5

name side effects of reversible anticholinesterases

Answer 5

• excessive muscarinic (parasympathetic) stimulation
  
  • salivation, lacrimation, miosis, diarrhea, bradycardia
• excessive nicotinic stimulation
  
  • muscle weakness and paralysis
• chemical warfare
  
  • used as nerve gas to induce muscle weakness + paralysis; respiratory paralysis
  • treated with atropine

Question 6

malathion

Answer 6

• function
  
  • irreversible anticholinesterase
• moa
  
  • organophosphate groups irreversibly bind to active portions of AChE to form an extremely stable complex, which prevents ACh breakdown
• clinical uses
  
  • none, very toxic
• side effects
  
  • increased ACh stimulates receptors causing muscle paralysis + death
    
    • effects overcome with synthesis of new AChE which may take up to 6 weeks

Question 7

succinylcholine

Answer 7

• function
  
  • neuromuscular nicotinic agonist
• moa
  
  • depolarizing neuromuscular blocker that prevents muscle contraction by activating nAChR
  • it is the only drug that activates the neuromuscular receptor
• clinical use
  
  • produces muscle paralysis during a short duration/surgery procedure
• side effects
  
  • drug is metabolized by pseudocholinesterase
    
    • some individuals have genetic defect of this enzyme, longer duration of drug (malignant hyperthermia)

Question 8

pancuronium

Answer 8

• function
  
  • neuromuscular nicotinic antagonist
• moa
  
  • competitive antagonist of ACh at the nAChR on skeletal muscles
  • binds to and occupies the nAChR at the NMJ
  • has no action of its own but prevents ACh from binding and exerting its contractile effects; causes paralysis
• clinical use
  
  • induction of flaccid paralysis in surgery
• side effects
  
  • hypertension, apnea, bronchospasm, salivation, respiratory failure
  • paralyzing effects overcome by increasing ACh levels; neostigmine

Question 9

name the muscarinic agonists (parasympathomimetric)

Answer 9

• bethanechol
  
  • almost completely selective for muscarinic receptors
• methacholine
  
  • 3x resistant to hydrolysis by AChE and has little affinity for nicotinic receptors
• acetylcholine
• pilocarpine

Question 10

name moa of muscarinic agonists

Answer 10

• activate the activity of muscarinic acetylcholine receptors

Question 11

name clinical uses + side effects of pilocarpine

Answer 11

• treats glaucoma
  
  • activates mAChR on circular muscles of eye, causing miosis (constriction). This enhances drainage of aqueous humor of eye, thus decreasing intraocular pressure
  • treats dry mouth in Sjogrens Syndrome
• side effect:
  
  • negligible since it is localized

Question 12

name clinical uses + side effects of bethanechol

Answer 12

• clinical uses
  
  • stimulates GI and urinary tract motility; assists in bladder emptying
• side effects
  
  • miosis, bradycardia, salivation, bronchoconstriction

Question 13

name clinical uses of methacholine

Answer 13

• clinical uses
  
  • inhalation of mathacholine results in bronchoconstriction
    
    • used to diagnose asthma
      
      • asthmatics are more sensitive to the bronchial secreting actions of methacholine
      • asthmatics will respond at a lower dose than non-asthmatic patients

Question 14

atropine

Answer 14

• function
  
  • muscarinic antagonist
• moa
  
  • binds to muscarinic receptors and prevents ACh from exerting its effects (competitive antagonists). This allows sympathetic responses to predominate
• clinical uses
  
  • produce pupil dilation for opthamological examination
  • reverse bradycardia caused by excessive vagal tone
  • inhibit excessive salivation + mucous secretion
  • counteract muscarine poisoning
  • reduces GI motility, bladder motility and sweating
  • reduces salivation, lacrimation, urination
• side effects (excessive sympathetic effects)
  
  • cardiac arrhythmias, rasied intraocular pressure, tachycardia, constipation