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Pharm 2024 > PPT 7/8 Cholinomimetics > Flashcards

PPT 7/8 Cholinomimetics Flashcards

exam 2

1
Q

What do cholinomimetic agents do?

A

ACh receptor stimulants and cholinesterase inhibitors - mimic the effect of ACh

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2
Q

What are the classifications of cholinomimetic agents?

A

Muscarinic and nicotinic - based on which receptor activated

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3
Q

Differentiate between direct and indirect-acting cholinoceptor stimulants

A

Direct-acting - agonists of receptors (choline esters and alkaloids)
Indirect-acting - cholinesterase inhibitors, prolonging ACh in the synapse (reversible and irreversible)

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4
Q

Where are muscarinic receptors found?

A

Nerve, heart and smooth muscle, and glands and endothelium

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5
Q

Where are nicotinic receptors found?

A

Neuromuscular end plate, skeletal muscle, and autonomic ganglion cells

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6
Q

Muscarine mimics the effect of what?

A

Parasympathetic nerve discharge
- Parasympathomimetic

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7
Q

Where does the action of muscarinic drugs take place?

A

Action of the alkaloid took place at effector cells, not those in the ganglia

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8
Q

What is given to treat muscarinic excess? Why?

A

Atropine 1-2mg IM - blocks muscarinic receptors

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9
Q

Where does the action of nicotinuc drugs take place?

A

Stimulates autonomic ganglia and skeletal muscle NMJ, not effector cells

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10
Q

Differentiate between transmembrane signaling in the cholinoceptors

A

Muscarinic - G-protein linked
Nicotinic - Ion channel

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11
Q

Which drugs are esters of choline?

A

Ach, Methacholine, Succinylcholine (Sux), Carbachol, and Bethanechol

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12
Q

Which drugs are alkaloids?

A

Muscarinic: Muscarine, Pilocarpine (betel nut)
Nicotinic: Nicotine, Lobeline

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13
Q

Esters of choline solubility

A

Permanently charged – insoluble in lipids (don’t cross barriers easily, can use patch)

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14
Q

Indication for administration of ACh

A

used primarily for pupilary constriction

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15
Q

Indication for administration of Methacholine

A

diagnosis of asthma

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16
Q

Indication for administration of Carbachol

A

Decreases IOP

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17
Q

Indication for administration of Bethanechol

A

Bladder dysfunction, reflux disease

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18
Q

What are the pharmacokinetics for esters of choline drugs?

A
  • A: Poor
  • D: Poor in CNS (hydrophilic)
  • M: Varies
    ACh: Rapid (5-20 seconds)
    Methacholine: 3x longer
    Carbachol/Bethanechol – resistant to hydrolysis
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19
Q

What are the pharmacokinetics for alkaloid drugs?

A

A: Pilocarpine, Nicotine, Lobeline = well
Nicotine is lipid soluble – transdermal delivery
Muscarine is less completely absorbed - charged
E: Kidneys – enhanced by acidification of urine

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20
Q

How do cholinomimetics affect the eye?

A

Muscarinic agonists – cause contraction of the pupil - PNS stimulus
Increase intraocular drainage

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21
Q

Differentiate between the types of glaucoma

A

Glaucoma = excessive amount of intraocular fluid, increased IOP
- Open-angle: Poor drainage in the eye’s drainage canals, but can still drain
- Angle-closure: Mechanical obstruction in the eye’s drainage system, iris has bulged forward to narrow and partially block the drainage angle

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22
Q

How do cholinomimetics affect the CV system?

A

Reduction in peripheral vascular resistance
Vasodilation – reduction in BP – reflexive increase in HR
- Large doses (overdose) - bradycardia

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23
Q

Which type of glaucoma is atropine contraindicated for? Why?

A

Angle-closure - atropine relaxes the ciliary muscle, causing complete obstruction of the drainage of the aqueous humor (medical emergency - blindness)

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24
Q

How do cholinomimetics affect the respiratory system?

A

Smooth muscle of bronchial tree contracted (better airway tone)
Tracheobronchial mucosa secretion increased

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25
Q

How do cholinomimetics affect the GI system?

A

Increased secretory and motor activity in gut - can treat post-operative ileus
Salivary and gastric glands stimulated
Sphincters relax

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26
Q

How do cholinomimetics affect the brain in the CNS?

A

Mainly muscarinic sites - muscarine doesn’t cross barrier easily
Nicotine
Mild alerting action (smoking) - release of dopamine, serotonin, GABA, NE
- Larger doses: tremor, emesis, stimulates respiratory center, convulsions, fatal coma

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27
Q

How do cholinomimetics affect the neuromuscular junction?

A
  • Immediate depolarization of endplate
  • Increased permeability to Na and K
  • Muscle contraction
  • If not readily hydrolyzed = depolarization blockade (flaccid paralysis) - Succinylcholine
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28
Q

How do cholinomimetics affect the spinal cord in the CNS?

A

Mainly nicotinic sites

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29
Q

What are the types of indirect-acting cholinomimetics?

A

Simple alcohols, carbamic acid esters of alcohols, and organic derivatives of phosphoric acid (organophosphates)

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30
Q

Why do organophosphates last for a long time?

A

Can form covalent bonds with AChE, somewhat irreversible

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31
Q

What are the indirect-acting cholinomimetics that we need to know?

A

Alcohols - edrophonium
Carbamates - neostigmine and pyridostigmine
Organophosphates - echothiophate

32
Q

What is echothiophate used for and how long does it last?

A

Glaucoma, 100 hours

33
Q

What is edrophonium used for and how long does it last?

A

MG, ileus, and arrhythmias; 5-15 min

34
Q

What is neostigmine used for and how long does it last?

A

MG, ileus; 0.5-2 hrs

35
Q

What is pyridostigmine used for and how long does it last?

A

MG, 3-6 hours

36
Q

What is the mechanism of indirect-acting cholinomimetics?

A

Targets ACh esterase (AChE), preventing the breakdown of ACh

37
Q

How can an organophosphate covalent bond be broken?

A

Need a strong nucleophile - Pralidoxime

38
Q

Why does Pralidoxime need to be given in the first few hours of organophosphate poisoning?

A

Aging
Breaks oxygen-phosphorous bond
Makes phosphorous-active site bond even stronger
Nucleophiles no longer effective

39
Q

What are the 4 major therapeutic uses of indirect-acting cholinomimetics?

A
  1. Disease of the eye - glaucoma
  2. GI and urinary tracts - ileus
  3. Neuromuscular junction - MG and anesthesia
  4. Atropine overdose
40
Q

MG is treated by which drug class?

A

Cholinesterase inhibitors

41
Q

Which drug is used to diagnose MG?

A

Edrophonium - can also be used to assess whether longer-lasting AChE inhibitors will work

42
Q

What is the pathophysiology of MG?

A

ACh receptors are internalized and degraded, leading to impaired muscle contraction
Weakness, fatigue, worsens with exercise

43
Q

How are indirect-acting cholinomimetics used in surgical anesthesia?

A

Neuromuscular blockades are frequently produced as an adjunct (pancuronium)
Relaxants - AChE inhibitors useful to reverse effects after surgery (neostigmine)

44
Q

How can atropine overdose be treated?

A

Overcome by increasing ACh present at NMJ; Competitive ACh receptor blockade - Physostigmine

45
Q

What are the symptoms of overdose of direct-acting muscarinic stimulants?

A

SLUDGE-M: Need atropine
Salivation, lacrimation, urination, defecation, GI motility, emesis, myosis

46
Q

What are the symptoms of overdose of cholinesterase inhibitors?

A

Similar to those of direct-acting agents
Miosis, salivation, sweating, brochial constriction, N/V/D

47
Q

How do you treat an overdose of cholinesterase inhibitors?

A
  • Vital sign maintenance
  • Decontamination
  • Atropine
  • Pralidoxime (organophosphates only) - pesticides
48
Q

What are the symptoms of overdose of direct-acting nicotinic stimulants?

A

Nicotine acute toxicity - fatal dose is 40mg
Ingestion (children) is usually followed by vomiting
HA, N/V, dizziness, breathlessness, collapse, loss of consciousness

49
Q

What are the symptoms of an overdose of mycetism/non-muscarinic agents?

A

Inhibits mRNA synthesis – 24 h symptom-free period followed by liver and kidney malfunction, death within 4-7 days - deadly nightcap mushroom

50
Q

What are the 4 kinds of antimuscarinic drugs?

A

Synthetic tertiary amine analogs
Synthetic quaternary amines
Scopolamine
Atropine

51
Q

What are the 2 kinds of antinicotinic drugs?

A

Ganglion blockers and NMJ blockers

52
Q

Atropine is a competitive inhibitor to ____

A

ACh

53
Q

What are the indications for the use of atropine?

A

Blocks the parasympathetic response
- Parkinson’s – adjunctive (L-DOPA main)
- Motion sickness – scopolamine (patch)
- Ophthalmic – topical tropicamide
- Asthma – Ipratropium bromide - atropine derivative
- Bradycardia – Atropine (IV)
- Poisonous mushrooms and organophosphate poisoning: atropine
- Used preoperatively (bradycardia)

54
Q

Why is atropine used preoperatively?

A
  • To help prevent vagal stimulation and potential bradycardia
  • Reduce respiratory secretions
  • Block unwanted GI activity
55
Q

What are the respiratory effects of atropine?

A

Blocks parasympathetic response of constricting airways → opens airway
Can treat asthma or COPD, but atrovent more useful

56
Q

What are the effects of atropine on the eyes?

A
  • Dilator
  • Cycloplegia – paralysis of the ciliary muscle (can’t switch from near/far vision (accommodation))
  • Decreased watering
  • Tropicamide - used for eye exams to dilate
57
Q

What are the effects of atropine on the heart?

A

Increases the heart rate after a transient bradycardia at the low dose

58
Q

Why can you see an initial dip in HR after giving atropine?

A

The theory is that it is due to atropine affecting muscarinic receptors on presynaptic cells more than on the ACh receptors of the effector cells

59
Q

What are the effects of atropine on salivary glands?

A

Diminishes gland excretory function

60
Q

What are the effects of atropine on urination?

A

Decreases micturition speed, or the speed of urination

61
Q

Summary of atropine effects

A
  • Decreases urine production, salivation, accommodation
  • Increases HR
62
Q

What are the contraindications to atropine?

A
  • Glaucoma patients - especially closed-angle
  • Elderly men (known prostatic hyperplasia) - swelling in the prostate gland because it decreases urination → urinary retention
63
Q

What are the signs and symptoms of atropine overdose?

A
  • hot as a desert (stopped sweating, hyperthermia)
  • bind as a bat (dilated pupils and loss of accommodation)
  • dry as a bone (no urination, salivation, sweating)
  • red as a beet (flushed skin)
  • mad as a hatter (atropine crosses BBB) - grabbing invisible objects, shaking, hallucinations
  • absent bowel sounds
64
Q

What is the treatment for atropine overdose?

A

Physostigmine - can produce dangerous CNS effects

65
Q

How do ganglion blockers work? Why aren’t they used anymore?

A
  • Block ACh at nicotinic receptors
  • Not used anymore because of lack of specificity - both sympathetic and parasympathetic (because ACh released in all ganglion)
66
Q

What are the two types of NMJ blockers?

A

Depolarizing muscle relaxant
Nondepolarizing muscle relaxants (Competitive blockers)

67
Q

What kind of NMJ blocker is succinylcholine?

A

Depolarizing muscle relaxant

68
Q

What are the clinical uses of succinylcholine?

A
  • Most often used to facilitate intubation
  • Electroconvulsive therapy
69
Q

What are the side effects of succinylcholine?

A

Fasciculation
Muscle pain
Hyperkalemia
Malignant hyperthermia
Apnea

70
Q

Why does succinylcholine have prolonged effects?

A

Not metabolized locally at NMJ - Metabolized by cholinesterase in plasma

71
Q

How does succinylcholine work?

A

Binds to ACh-R, causing continuous end-plate depolarization and muscle relaxation; works for 5-10 min

72
Q

Differentiate between phase I and phase II blocks

A

Phase I: depolarization and lack of repolarization
Phase II: longer-term, end plate repolarizes over time, muscle no longer reacting to succinylcholine; deeper block

73
Q

How do nondepolarizing muscle relaxants work?

A

Competitive antagonists: compete with ACh at binding site (ACh-R), but do not depolarize the motor end plate; curare derivatives

74
Q

What are the 3 examples of nondepolarizing muscle relaxants?

A
  • Long acting
    • Pancuronium
  • Intermediate acting
    • Atracurium
  • Short acting
    • Mivacurium
75
Q

What are the medications that reverse NMJ blockers?

A

Neostigmine (increases ACh at the synapse) and Sugammadex (for rocuronium and vecuronium)

Pharm 2024 (13 decks)

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