Cholinergic Transmission and Drugs

  1. Cholinergic transmission involves the release of the neurotransmitter _____________.
  2. The cholinergic receptors work on the ______________ nervous system.
  3. What are the two types of cholinergic receptors and what do the affect?
    • Muscarinic - stimulates smooth muscle and slows HR
    • Nicotinic - affects skeletal muscle
  4. True or False:
    Most of the drugs which work on cholinergic receptors will give activation to the postsynaptic receptor.
  5. __________ receptors have two subtypes-one at the ______________ junction of skeletal muscle, the other within __________ and the CNS.
    • Nicotinic
    • neuromuscular
    • ganglia
  6. _________ receptors are distributed within both peripheral and central nervous system.
  7. Cholinergic Agents:
    • Drugs that are working on the muscarinic receptors; muscarinic agonist
    • Direct or Indirect
  8. Cholinergic Agents:
    Direct acting -
    act on the receptors to activate a tissue response
  9. Cholinergic Agents:
    Indirect acting -
    inhibit the action of the enzyme cholinesterase
  10. What are the major uses of cholinergic agents?
    • Stimulates bladder and GI tone
    • Constrict pupils (miosis)
    • Neuromuscular transmission
  11. Cholinergic Agents
    Bethanecol (Urocholine):
    • Selective to muscarinic receptors
    • Mimic the action of acetylcholine
  12. Uses of Bethanecol (Urocholine):
    • For treatment of urinary retention
    • Dose (Usual) 25 mg PO TID (10 – 50 mg per dose)
    • Increase peristalsis, take on empty stomach
  13. Contraindications of Bethanecol (Urocholine):
    Asthma, peptic ulcer disease, intestinal obstruction, hyperthyroidism
  14. Cholinergic Agents(Parasympathomimetics)
    Pilocarpine (Pilocar):
    • Opthalmic or Oral
    • Direct muscarinic Agonist
  15. Uses of Pilocarpine (Pilocar):
    Oral: Used to relieve dry mouth after head and neck radiation
  16. What are the actions of Cholinergic Blocking Agents (Parasympathomimetics)?
    Inhibit the action of ACH receptors
  17. What systems are affected by Cholinergic Blocking Agents (Parasympathomimetics) and by what action is this achieved?
    • Affects the heart, respiratory tract, GI tract, bladder, eye, and exocrine glands
    • By allowing the sympathetic nervous system to dominate
  18. What are the effects of Cholinergic Blocking Agents (Parasympathomimetics)?
    Decrease GI motility, decrease salivation, dilation of pupils, increase in pulse rate
  19. Anticholinergics are widely used state some of the different uses:
    • Pre - op medications
    • Bradycardia
    • GI/Urinary antispasmodic
    • IBS
    • Motion sickness
  20. Anticholinergics
    What are different souces of Atropine?
    • Source (Alkaloid)
    • Atropa Belladona
    • Daktura Stramonium (jamestown weed)
  21. True or False:
    The blockade of Atropine is competitive and reversible. Give an explanation.
    • True
    • If the concentration of acetylcholine in the vicinity of the blocked receptor can be increased, acetylcholine will displace atropine and transmission will be restored
  22. What are the actions of Atropine?
    • Inhibits ACH
    • Blocks vagal effects on SA node and AV node
    • Increases conduction and HR
  23. What is the prototype blocker of muscarinic receptors?
    • Atropine
    • Hallucinatory effects of atropine and its relatives are often sought out by recreational drug users
  24. Atropine Effects (5):
    • Mad as a hatter
    • Blind as a bat
    • Dry as a bone
    • Red as a beet
    • Hot as a pistol
  25. Mad as a Hatter effect of Atropine:
    • Drug-induced delirium is one of the most dangerous aspects of atropine poisoning in adults
    • Result in self-destructive acts, such as leaping out of windows or pulling out intravenous tubing.
  26. Blind as a Bat, the three effects Atropine has on vision:
    • Cholinergic tone to the sphincter iridis muscle of the iris tends to contract the pupil
    • Interruption of that tone leads to pupillary dilation (mydriasis)
    • Unrelenting mydriasis results in photophobia
  27. Dry as a Bone effect of Atropine:
    • Manifested by a blockade of cholinergic tone to the salivary glands
    • Decreased salivation, dry mouth, intense thirst and difficulty in swallowing
    • Skin is also dry because of a blockade of sweating
  28. Red as a Beet effect of Atropine:
    • Mechanism of this response is unknown
    • Flushing
    • Not attributed to blockade of muscarinic receptors
  29. Hot as a Pistol effect of Atropine:
    • Elevated body temperature
    • May reach life-threatening levels
  30. Atropine (Dosing)
    Low Dose 0.5mg symptoms:
    Slight decline in HR, inhibition of sweating, some dry mouth
  31. Atropine (Dosing)
    1 mg Dose symptoms:
    Increased heart rate, definite dry mouth, thirst
  32. Atropine (Dosing)
    2 mg Dose symptoms:
    Rapid heart rate, palpitations, dilated pupils, blurring of near vision
  33. Atropine (Dosing)
    5 mg Dose symptoms:
    Rapid HR, palpitations, dilated pupils, blurring of near vision, difficulty speaking, headache, dry hot skin reduced intestinal peristalsis
  34. Atropine (Dosing)
    10 mg Dose symptoms:
    Rapid HR, palpitations, dilated pupils, difficulty speaking, headache, dry hot skin reduced intestinal peristalsis, very blurred vision, ataxia, reslestness and hallucinations, possible coma
  35. Anticholinergic
    What is the method of action of Dicyclomine (Bentyl)?
    Inhibits ACH on muscarinic receptors and decreases GI motility
  36. Anticholinergic
    What are the uses of Dicyclomine (Bentyl)?
    • Irritable Bowel Syndrome
    • Constipation, urinary retention and dry mouth
  37. What is the dose for Dicyclomine (Bentyl)?
    • 10-20 mg PO TID AC
    • PO-orally
    • TID-3 X Day
    • AC-before meals
  38. Anticholinergic
    What is the method of action of Glycoperalate (Robinul) and what are it's uses?
    • Similar to bentyl method of actio
    • inhibits ACH on muscarinic receptors and decreases GI motility
    • Uses: Pre-op to decrease secretions and GI disorders
  39. What are the doses of Glycopralate (Robinul)?
    • IV and Oral (1-2 mg)
    • Also used when dislodging something stuck in the throat
  40. Effect of a Scopolamine Patch:
    Give examples:
    • ACH benefit the CNS and help for motion sickness
    • Dramamine and Bonine oral
    • Crosses the blood brain barrier
  41. What are some side effects of Scopolamine Patch?
    Dry mouth, visual disturbances, and pupil dilation
  42. Contraindications to the Anticholinergics:
    • Narrow angle glaucoma
    • Hypertrophy of the prostate
    • Atony of the bladder
    • Atony of the GI tract
    • Careful in elderly
  43. Other Drugs with Anticholinergic Effects (other classes):
    • Tricyclic antidepressants
    • Phenothiazine antipsychotics
    • Dibenzoxaoine antipsychotic agents
    • H1 receptor blocking agents
  44. What drugs can be used to alleviate the symptoms associated with anticholinergic effects?
    • Muscanrinic agonists:
    • Pilocarpine
    • Bethanechol
  45. NMB
    Neuromuscular-Blocking Agent
  46. Cholinergic receptors are close to the enzyme _______________.
  47. Acetylcholinesterase is an enzyme that is responsible for rapid hydrolysis of ACH to __________ and _________.
    • acetic acid
    • choline
  48. True or False:
    Choline re-enters motor nerve endings to again participate in the synthesis of new acetylcholine.
  49. Rapid hydrolysis of ______ prevents sustained depolarization.
  50. Nicotinic Acetylcholine Receptor (nAChR)
    Up-regulation can cause:
    Spinal Cord Injury, CVA, Prolonged exposure to NMB drugs, Guillain-Barre syndrome
  51. Nicotinic Acetylcholine Receptor (nAChR)
    Down-regulation can cause:
    Myasthenia Gravis, Organophosphate Poisonings
  52. What are some key points to take into account when using NMBs?
    • Types of patients
    • Dose
    • Length of paralysis
    • Side effect profile
  53. When should you use NMBs?
    • Tracheal intubation
    • Surgery
    • Mechanical ventilation
    • Manage increased intracranial pressure (ICP) ex: head-injured patients
    • Decreased oxygen consumption
    • NMBs do not relieve pain or produce sedation
  54. What are the two classifications of NMBs?
    • Depolarizing
    • Nonpolarizing
  55. Action of Depolarizing NMBs:
    • Bind to ACh receptor on the motor end-plate
    • Stimulates depolarization
    • Block of nuerotransmission and muscle paralysis
  56. Action of Non-Depolarizing NMBs:
    • Bind to Ach receptors on the motor end-plate
    • Prevent Ach from stimulating receptors
    • Resulting in muscle paralysis
  57. Give an example of a Depolarizing NMB:
    Succinylcholine (Quelicin)
  58. Give examples of Non-depolarizing NMBs:
    • Cisatracurium (Nimbex)
    • Vecuronium (Norcuron)
    • Pancuronioum (Pavulon)
    • Atracurium Besylate (Tracurium)
    • Rocuronium (Zemuron)
    • Doxacurium (Nuromax)
    • Mivacurium (Mivacron)
  59. Succinylcholine (Quelicin) types of admission:
    • I.M. or I.V.
    • I.M.- Intramuscular
  60. Succinylcholine (Quelicin)
    Onset of action?
    Duration of action?
    • Short acting
    • Onset of action: 30-60 seconds
    • Duration of action: 5-8 minutes
  61. What is the dosage of Succinylcholine (Quelicin) when used in Rapid sequence Intubation (RSI)?
    • Rapid Sequence Intubation (RSI): 1mg/kg
    • Intermittent I.V. dose: 0.6mg/kg over 10-30 seconds, max dose 150mg
    • Continuous I.V. dose: 2.5mg/min; not routinely done
  62. What are adverse effects of Succinylcholine?
    • Respiratory Depression
    • Anaphylaxis (rare) - less than 1%
    • Cardiac Arrest
    • Bradycardia
    • Hypotension
    • Hyperkalemia
  63. Non-Depolarizing NMBs
    • Rocuronium (Zemuron)
    • Mivacurium ( Mivacrom)
    • Cisatracurium (Nimbex)
    • Vecuronium (Norcuron)
    • Pancuronium (Pavulon)
    • Atracurium Besylate (Tracurium)
  64. Rocuronium

    • B) Usage:I.V. use
    • Type of acting: Short acting
    • Onset: 1-3 minutes
    • Duration of action: 31 minutes
    • Used in Rapid Sequence Intubation (RSI)
  65. Precautions when using Rocuronium:
    • Pulmonary disease
    • Hepatic impairment
  66. Rocuronium

    • C) Dose: RSI: 0.6-1.2 mg/kg - usually a bolus
    • Continuous IV infusion: .01-.012 mg/kg/min - Not routine
    • Diluents: NS, D5W
    • Adverse Effects: Hypotension, HTN
  67. Primary use of Mivacurium (Mivacrom):
    Induction of neuromuscular blockade, During surgery as an adjunct to general anesthesia and to facilitate tracheal intubation or mechanical ventilation
  68. Intial Dose of Mivacurium used for intubation:
    initial, for intubation, 0.15 mg/kg IV bolus over 5-15 sec OR 0.2 mg/kg IV bolus over 30 sec OR 0.25 mg/kg IV bolus in divided doses (0.15 mg/kg followed in 30 sec by 0.1 mg/kg)
  69. Adverse effects of Mivacurium:
    • Flushing, Bradyarrhythmia, Cardiac dysrhythmia, Hypotension, Tachyarrhythmia, Prolonged neuromuscular block
    • Not used in patients with cardiac issues (arrythmias)
  70. Maintenance dosage of Mivacurium:
    • maintenance, 0.1 mg/kg IV bolus 15-25 min after initial dose
    • maintenance, 9-10 mcg/kg/min continuous IV infusion after initial dose, upon early evidence of spontaneous recovery
    • maintenance, 4 mcg/kg/min continuous IV infusion if initiated simultaneously with administration of initial dose
  71. Cisatracurium (Nimbex)
    Type of use
    Quikness of action:
    Onset of action:
    Duration of action:
    • I.V. use only
    • Intermediate acting
    • Onset of action: 2-3minutes
    • Duration of action: 30-40 minutes
  72. What is the drug of choice when dealing with:
    Significant renal dysfunction (CrCl <30m/min)
    Hepatic Failure
    Concurrent corticosteroid administration (>72 hours)
    History of asthma or bronchospasm?
    Cisatracurium (Nimbex)
  73. Cisatracurium (Nimbex)

    • B) Dose: Continuous I.V. infusion: 0.06 – 0.2mg/ kg/ hr
    • Diluents: NS,D5W
    • Preparation: Add 200mg of Nimbex in 200ml D5W
  74. Adverse effects of Cisatracurium (Nimbex)?
    • Bradycardia
    • Hypotension
    • Flushing
  75. Vecuronium (Norcuron):

    • A) Type of use: IV use only
    • Quickness of action: Intermediate acting Onset of action: 2-3 minutes
    • Duration of action: 25-40 minutes
  76. What is the Durg of choice when dealing with a patient with solely renal failure?
    Vercuronium (Norcuron)
  77. Vecuronium (Norcuron)

    • C) Dose:
    • I.V. bolus: 0.08-0.1mg/kg
    • Continuous I.V. infusion: 0.05 – 0.1mg / kg / hr

    • Diluents:
    • NS
    • D5W

    • Preparation: Add 50mg of Vecuronium in 100ml D5W
    • Train-of-four used
  78. Pancuronioum (Pavulon)

    • C) Type of use: IV use only
    • Quickness of action: Intermediate acting
    • Onset of action: 2-3 minutes
    • Duration of action: 60-90 minutes sometimes longer
  79. What is a contraindication to Pancronium (Pavulon)?
    • Precautions: Patients with renal and/or hepatic impairment
    • Ideal agent only in the perfect patient: No renal impairment
  80. Pancuronioum (Pavulon):

    • A) Dose:
    • Intermittent I.V. dose: 0.1 to 0.2 mg/kg (usually 0.1mg) every 1-3 hours
    • Continuous infusion: Loading dose: 0.04 to 0.10mg/kg, followed by 1 to 1.7mcg/kg/min
    • Intermittent dosing is preferred due to Pancuronium T ½ is 110minutes
    • Diluents:
    • NS
    • D5W
    • Preparation: 12.5 to 25mg of Pancuronium in 250ml
  81. What are the adverse effects of Pancronioum (Pavulon)?
    • Tachycardia
    • HTN
    • Excessive salivation
  82. Type of use:
    Quickness of action:
    Onset of action:
    Duration of action:
    I.V. bolus:
    I.V. infusion:
    • Type of use: I.V. use
    • Quickness of action: Intermediate acting
    • Onset of action: 2.5-5 minutes
    • Duration of action: 20-45 minutes
    • Dose:
    • I.V. bolus: 0.4 to 0.5mg/kg
    • Continuous I.V. infusion: 9 to 10mcg/kg/min
  83. What is a precaution when using Atracurium Besylate (Tracurium)?
    Precautions: Not used in renal failure patients due to toxic metabolite
  84. Atracurium Besylate (Tracurium)
    • Diluents:
    • NS
    • D5W
    • May be given undiluted by I.V. bolus
  85. What are the adverse effects of Atracurium Besylate (Tracurium)?
    • Bradycardia
    • Hypotension
    • Itching
  86. What are the monitoring parameters for all NMBs?
    • HR
    • BP
    • RR
    • Electrolytes
    • Degree of muscle relaxation via a peripheral nerve stimulator (train –of- four)
    • Renal function
    • Liver function
  87. What are some of the warnings/precatutions when using NMBs?
    Ventilation must be supported during neuromuscular blockade

    • Electrolytes abnormalities may potentiate NMBs effects
    • Severe hyponatremia
    • Severe hypocalcemia
    • Severe hypokalemia
    • Hypermagnesemia

    Hypercalcemia antagonize NMBs effect
  88. Give examples of drugs and or physiological states which increase the neuromuscular blocking effect of NMBs:
    Aminoglycosides, Clindamycin, Colistin, Desflurane, Isoflurane, Lincomycin, magnesium,Piperacillin, Sevoflurane Suxamethonium, Ketamine, Digoxin (arrhythmias)

    • Hypermagnesemia
    • Hypocalcemia
    • Hypokalemia
  89. Give examples of drugs and or physiological states which decrease the neuromuscular blocking effect of NMBs:
    Anticholinesterases, carbamazepine(Except Mivacurium), phenytoin, Theophylline

    • Hypercalcemia
    • Hyperkalemia
  90. Things to know when using NMBs on a patient:
    • Adequate sedation and analgesia must be achieved before starting a paralytic, sedation around the clock
    • Train-of-Four (baseline first, 1-2 twitches)
    • Concurrent medications and disease states
Card Set
Cholinergic Transmission and Drugs
Cholinergic Transmission and Drugs