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Nervous System Pharmacology > Cholinergic's > Flashcards

Cholinergic's Flashcards

1
Q 
Parasympathetic Effects of Acetylcholine: 
Cardiovascular 
GI/GU
Glands
Respiratory 
Ocular
A

Decrease HR/ AV/ contractility
Vasodilation
Increase GI/GU motility, secretion, sphincter relaxation & Increase micturition
Increase glandular secretion
Increase Bronchoconstriction/ respiratory secretions
Miosis/ ciliary muscle contraction – accommodation for near vision

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2
Q

What are the sympathetic and parasympathetic effects elicited by Ach?

A

Sympathetic- vasoconstriction, sweating

Parasympathetic- bradycardia; miosis; GI motility/ urination; glandular secretions

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3
Q

What is the rate limiting step in Ach hydrolysis

A

Quaternary ammonium attracted to anionic site
Acyl O attacked by serine at esteratic site
Ester bond cleavage and liberation of choline (enzyme now acylated)
Acetate removed from AchE–> reactivation **RLS

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4
Q

Tetrodotoxin action

A

Inhibits Na channel/ AP

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5
Q

Saxitoxin action

A

Inhibits Na channel/ AP

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6
Q

Black Widow action

A

Stimulate Ach release

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7
Q

Botulism Toxin action

A

STOPS Ach release

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8
Q

What are the physiologic effects of muscarinic AGONISTS?

A

SLUDE +BBB (salivation, lacrimation, urination, defecation, emesis, bronchoconstriction, bradycardia, blurred vision)

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9
Q

What is that “Bradycardia caveat in “SLUDE BBB”

A
  • Bradycardia at high dose only (Low dose reflex > drug HR in response to vasodilation)
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10
Q

What drug can be used to reverse or block the effects of a muscarinic AGONIST?

A

Atropine

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11
Q

Pilocarpine:
MOA
Specific Use

A

Muscarinic Agonist

Wide angle glaucoma

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12
Q

What are 5 contraindications for all muscarinic agonists

A

1) Asthma
2) COPD
3) CV disease
4) Hyperthyroid
5) peptic ulcer

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13
Q

Carbachol:
MOA
Specific Use

A

Muscarinic Agonist

Wide angle glaucoma

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14
Q

Bethanecol:
MOA
Specific Use

A

Muscarinic Agonist

GI/GU motility–treats urine retention, distention, etc.

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15
Q

Muscarine:
MOA
What’s the story here?

A

Mushrooms, accidental ingestion

Need atropine for reversal

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16
Q 
What are the physiologic effects of Muscarinic ANTAGONISTS: 
CV
GI/GU
Ocular 
Sweating
CNS
A 
Increase CV function
Decrease GI/GU motility
Increase bronchi dilation 
Cyclopedia/ Mydriasis 
Decrease sweating 
CNS Depression
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17
Q

What are 5 ADR’s associated with all Muscarinic ANTAGONISTS? Which Drug is used to reverse them?

A 
Red as a beet 
Dry as a bone 
Blind as a bat 
Hot as a fire 
Mad as a hatter

Reverse with Physostigmine

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18
Q

What are 3 contraindications associated with all Muscarinic ANTAGONISTS?

A
  1. glaucoma (esp narrow angle)
  2. cardiac disease
  3. Prostatic hypertrophy
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19
Q

Homotropine:
MOA
Therapeutic use

A

Bind Muscarinic receptors and INHIBIT Ach effects

Optho Exam: mydriasis, cycloplegia

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20
Q

Cyclopentolate:
MOA
Therapeutic Use

A

Bind Muscarinic receptors and INHIBIT Ach effects

Optho Exam: mydriasis, cycloplegia

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21
Q

Tropicamide:
MOA
Therapeutic Use

A

Bind Muscarinic receptors and INHIBIT Ach effects

Optho Exam: mydriasis, cycloplegia

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22
Q

Atropine:
MOA
Therapeutic Use

A

Bind Muscarinic receptors and INHIBIT Ach effects

Reverses anticholinesterases (AchEi) + muscarinic agonist

Note: toxic dose stimulates CNS,
> toxic dose will depress CNS

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23
Q

Glycopyrrolate:
MOA
Therapeutic Use

A

Bind Muscarinic receptors and INHIBIT Ach effects

Reverses Anticholinesterases

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24
Q

Benztropine:
MOA
Therapeutic Use

A

Bind Muscarinic receptors and INHIBIT Ach effects

Parkinsonism

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25
Q

Trihexylphenidyl:
MOA
Therapeutic Use

A

Bind Muscarinic receptors and INHIBIT Ach effects

Parkinsonism

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26
Q

Scopolamine:
MOA
Therapeutic Use

A

Bind Muscarinic receptors and INHIBIT Ach effects

Administered as transdermal patch to prevent motion sickness

Note: CNS Depressant in therapeutic doses

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27
Q

Ipratropium:
MOA
Therapeutic Use

A

Bind Muscarinic receptors and INHIBIT Ach effects

COPD, Asthma

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28
Q

Tiotropium:
MOA
Therapeutic Use

A

Bind Muscarinic receptors and INHIBIT Ach effects

COPD, Asthma

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29
Q

Darifenacin:
MOA
Therapeutic Use

A

Bind Muscarinic receptors and INHIBIT Ach effects

Overactive bladder in children

30
Q

Amitriptyline

A

Has significant anti-muscarinic activity and can cause anti-muscarinic toxicity

31
Q

H1 Receptor antagonists

A

Has significant anti-muscarinic activity and can cause anti-muscarinic toxicity

32
Q

Phenothiazines

A

Has significant anti-muscarinic activity and can cause anti-muscarinic toxicity

33
Q

What is the MOA for all non-depolarizing (competitive) NMJ Blockers?

A

Bind Nm Receptor at NMJ–> Displace Ach–> Induce Paralysis without polarization

34
Q

What is the therapeutic indication for all Non-Depolarizing/ Competitive NMJ Blockers?

A

Induce muscle paralysis as an adjunct to anesthetic during surgery

35
Q

What 3 drugs enhance the effects of non-depolarizing/ competitive NMJ blockers

A
  • Halogenated Hydrocarbon Anesthetics
  • Aminoglycoside Antibiotics
  • Ca++ Channel Blockers
36
Q

Which drugs can be used to reverse the effects of non-depolarizing/ Competitive NMJ Blockers?

A

Anticholinesterase Drugs (*NEOSTIGMINE, EDROPHONIUM, PYRIDOSTIGMINE)

37
Q

What are three commonalities amongst all non-depolarizing/ Competitive NMJ blockers?

BBB?
Molecular structure?
Administration?

A
  • NO CROSS BBB
  • Quaternary Ammonium Salts
  • IV admin only
38
Q

Curare:
MOA
Duration of activity

A

NONDEPOLARIZING/ COMPETATIVE NMJ BLOCKER

Long acting

39
Q 
Tubocurarine: 
MOA 
Duration of activity 
Metabolism*
ADR*
A

NONDEPOLARIZING/ COMPETATIVE NMJ BLOCKER

  • Long acting
  • Hepatic metabolism, renal excretion

ADR: Partial ganglionic block (histamine release–> bronchospasm, hypotension)

40
Q

Doxacurium:
MOA
Duration of activity

A

NONDEPOLARIZING/ COMPETATIVE NMJ BLOCKER

- Long acting

41
Q

Panacuronium:
MOA
Duration of activity

A

NONDEPOLARIZING/ COMPETATIVE NMJ BLOCKER

- Long acting

42
Q

Gallamine:
MOA
Duration of activity
ADR*

A

NONDEPOLARIZING/ COMPETATIVE NMJ BLOCKER
- Long acting

ADR: Blocks cardiac Vagus N 
-	Tachycardia 
-	~HTN
-	^ Cardiac Output 
"Galloping Heart!"
43
Q

Cisatracurium:
MOA
Duration of action
Metabolism*

A

NONDEPOLARIZING/ COMPETATIVE NMJ BLOCKER
- Intermediate duration

Metabolized by plasma esterase; has fast onset

44
Q

Rocuronium:
MOA
Duration of Action

A

NONDEPOLARIZING/ COMPETATIVE NMJ BLOCKER

- Intermediate duration

45
Q

Vecuronium:
MOA
Duration of Action

A

NONDEPOLARIZING/ COMPETATIVE NMJ BLOCKER

- Intermediate duration

46
Q

Mivacurium:
MOA
Duration of action
Metabolism

A

NONDEPOLARIZING/ COMPETATIVE NMJ BLOCKER
- Short duration of action

Metabolized by pseudocholinesterase (plasma cholinesterase)

47
Q

Common ADR Associated with all Non-Depolarizing/Competative NMJ Blockers

A

Prolonged muscle paralysis & apnea

48
Q

Succinylcholine:
MOA
Therapeutic Use

A

Depolarizing NMJ Blocker:

Prolonged binding to Nm (Stable Nm Agonist)

Phase I Depolarization block–> muscle paralysis–>
~Phase II depolarization block (low butrylcholinesterase; too high dose)

Rapid muscle paralysis for endotracheal intubation

49
Q

Succinylcholine:
Metabolism
Route of administration
BBB?

A

Butrylcholinesterase

IV Admin

Does not cross BBB

50
Q

Succinylcholine ADR***

A
  • Malignant hypepyrexia
  • Muscle rigidity
  • Hyperthermia
  • HTN
  • Tachycardia
  • Genetic predisposition
  • Tx. DANTROLINE
51
Q

2 Drugs that prolong/ exaggerate action of succinylcholine

A
  1. Anticholinesterases (Neostigmine)

2. Halothane anesthetics

52
Q

What are two DEPOLARIZING NMJ BLOCKING Drugs?

A
  1. Succinylcholine

2. Nicotine

53
Q

Nicotine:
MOA
Physiologic effects

A

Low Dose: STIMULATES Nn, Nm
High Dose: BLOCKS Nn, Nm

Excessive SLUDE BB, Tachy, HTN, muscle fasciculation’s

54
Q

Acute Nicotine Poisoning:
Manifestation
Drug for reversal

A

Excessive SLUDE BB (stimulation)–> Brain stem Depression–> Respiratory Failure

Reverse with ATROPINE

55
Q

Edrophonium:
MOA
Therapeutic Use
Does it cross BBB?

A

Reversible Anticholinesterase

  • Reverse effects of competitive non-depolarizing NMJ blockers (not succinylcholine)
  • Quaternary Ammonium, no cross BBB
56
Q

Tacrine
MOA
Therapeutic Use

A

Reversible Anticholinesterase

Alzheimers–crosses BBB

57
Q

Rivastigmine
MOA
Therapeutic Use

A

Reversible Anticholinesterase

Alzheimers–crosses BBB

58
Q

Donepezil
MOA
Therapeutic Use

A

Reversible Anticholinesterase

Alzheimers–crosses BBB

59
Q

Physostigmine
MOA
Therapeutic Use
Cross BBB?

A 
Reversible Anticholinesterase
CARBAMOYL ESTER LINKAGES
Carbamylate esteric site on AchE causes increase in Ach
- Reverse atony of smooth muscle 
- Reverse non-depolarizing NMJ blockers
- Crosses BBB
60
Q

Neostigmine
MOA
Therapeutic Use
Cross BBB?

A 
Reversible Anticholinesterase
CARBAMOYL ESTER LINKAGES
Carbamylate esteric site on AchE causes increase in Ach
- Reverse atony of smooth muscle 
- Reverse non-depolarizing NMJ blockers
- No cross BBB
61
Q

Pyridostigmine
MOA
Therapeutic Use

A

Reversible Anticholinesterase
CARBAMOYL ESTER LINKAGES
Carbamylate esteric site on AchE causes increase in Ach
- Reverse non-depolarizing NMJ blockers

62
Q

Isoflurophate
MOA
Therapeutic Use

A

Anticholinesterase
IRREVERSIBLE!!!! ORGANOPHOSPHATE INHIBITORS
Phosphorylate esteratic site of AchE

63
Q

Echothiophate
MOA
Therapeutic Use

A

Anticholinesterase
IRREVERSIBLE!!!! ORGANOPHOSPHATE INHIBITORS
Phosphorylate esteratic site of AchE
- Second Line Tx.
Chronic wide angle glaucoma /Acute angle glaucoma (short term tx)

64
Q

Insecticides
MOA
Therapeutic Use

A

Anticholinesterase
IRREVERSIBLE!!!! ORGANOPHOSPHATE INHIBITORS
Phosphorylate esteratic site of AchE

65
Q

Nerve Gas
MOA
Therapeutic Use

A

IRREVERSIBLE!!!! ORGANOPHOSPHATE INHIBITORS

Phosphorylate esteratic site of AchE

66
Q

Pralidoxime (2-PAM):
MOA
Therapeutic Use

A

Cholinesterase Reinactivator:
Pulls organic phosphate off esteratic site of AchE

Administer soon after poisoning to beat aging

67
Q

What happens when organophosphate inhibitors age?

A

Loss of alkyl or alkoxyl group makes phosphorylated enzyme more stable–> Increases irreversible properties

68
Q

How does Anticholinesterase poisoning present and what drugs can be used to reverse it?

A

Excessive SLUDE BBB; delayed neurotoxicity

REVERSE: ATROPINE, PRALIDOXIME

69
Q

Which drug is used to identify whether patient has Myasthenia Gravis or Cholinergic Crisis?

A

Edrophonium, then look for muscle strength:
MG: Increase muscle strength, give pt more AchEi
Cholinergic Crisis: Decrease Muscle Strength, give patient less anti cholinesterase

70
Q

How do you treat myasthenia gravis?

A

Neostigmine, Pyridostigmine

Nervous System Pharmacology (3 decks)

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