Pharmacology Of NMJ + NMJ CIS Flashcards

1
Q

_________ is a drug/primary neurotransmitter at cholinergic nerve endings (preganglionic ANS, postganglionic parasympathetic, postganglionic sympathetic to thermoregulatory sweat glands, and somatic neuromuscular end plates

A

Acetylcholine

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2
Q

__________ = sympathomimetic drug that facilitates the release of catecholamines from adrenergic nerve endings

A

Amphetamine

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3
Q

_______ _______ is a bacterial toxin that enzymatically disables release of acetylcholine from cholinergic nerve endings

A

Botulinum toxin

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4
Q

What early neuromuscular blocking agent was one of the first used for muscular relaxation in general anesthesia and later led to the development of compounds like gallamine and pancuronium?

A

Curare

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5
Q

What are some of the ways that neuromuscular blockers are classified?

A
Mechanism of action
Duration of action
Speed of onset and offset of action
Selectivity of action and safety margin
Adverse effects
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6
Q

What type of NMJ blocking agent is curare?

A

Competitive (non-depolarizing)

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7
Q

Competitive (non-depolarizing) agents like curare operate by competing with ACh for binding to the receptor.

What type of paralysis do they cause?

A

Flaccid, relaxed paralysis

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8
Q

Competitive (non-depolarizing) agents like curare operate by competing with ACh for binding to the receptor.

What are some non-NMJ effects caused by these agents?

A

Ganglia, muscarinic blocking, histamine release

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9
Q

Competitive (non-depolarizing) agents like curare operate by competing with ACh for binding to the receptor.

How is this type of NMJ block reversed?

A

Acetylcholinesterase inhibitors

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10
Q

What type of NMJ blocking agent is succinylcholine?

A

Non-competitive (depolarizing)

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11
Q

What are the 2 phases associated with the MOA of non-competitive (depolarizing) NMJ blocking agents like succinylcholine?

A

Phase 1 block: membrane depolarization; transient fasciculations followed by paralysis

Phase 2 block: desensitization; membrane repolarizes, hyposensitive to ACh

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12
Q

T/F: Both competitive and non-competitive NMJ blocking agents can be reversed by administering acetylcholinesterase inhibitors

A

False; competitive inhibitors CAN be reversed by AChE inhibitors, but non-competitive CANNOT

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13
Q

What is the progression of paralysis due to blocking the NMJ? In what order do these muscles recover?

A

Small rapidly moving muscles (eyes, fingers), then limbs, the last is respiratory muscles

These are recovered in reverse order

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14
Q

General poisoning due to ________ occurs after ingestion of various species of puffer fish. It is lethal even in small doses

A

Tetradotoxin

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15
Q

What is the MOA of tetradotoxin?

A

Tetradotoxin blocks diffusion of sodium through sodium channels, thus preventing depolarization and propagation of action potentials in nerve cells

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16
Q

All of the observed toxicity of tetradotoxin is secondary to blockade of the _______ _________. It acts on the central and peripheral nervous systmes.

In recent studies using tetradotoxin therapeutically in conjunction with __________, local anesthetic effect can be prolonged.

However, clinical use of tetradotoxin may increase the incidence of toxicity

A

Action potential

Bupivacaine

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17
Q

What agent affecting the action nerve potential produces COMPLETE sensory block, and its effect on motor function differs with varying concentrations?

A

Bupivacaine

18
Q

Which of the following would you use to provide motor blockade for caudal, epidural, or nerve block, but muscle relaxation may be inadequate for operations in which complete muscle relaxation is ESSENTIAL?

A. 0.25% Bupivacaine
B. 0.5% Bupivacaine
C. 0.75% Bupivacaine
D. 0.5% Tetradotoxin
E. 0.75% Tetradotoxin
A

B. 0.5% Bupivacaine

19
Q

Which of the following agents would you use for caudal, epidural, or peripheral nerve block to produce incomplete motor block in which muscule relaxation is not important?

A. 0.25% Bupivacaine
B. 0.5% Bupivacaine
C. 0.75% Bupivacaine
D. 0.5% Tetradotoxin
E. 0.75% Tetradotoxin
A

A. 0.25% Bupivacaine

20
Q

Which of the following would you use to produce complete motor block, especially when performing epidural block in abdominal operations requiring complete muscle relaxation?

A. 0.25% Bupivacaine
B. 0.5% Bupivacaine
C. 0.75% Bupivacaine
D. 0.5% Tetradotoxin
E. 0.75% Tetradotoxin
A

C. 0.75% Bupivacaine

[note that you would NOT use this for epidural anesthesia for obstetrical procedures]

21
Q

A major cause of adverse reactions to ________ include excessive plasma levels, overdose, unintentional intravascular injection, or slow metabolic degradation

A

Bupivacaine

22
Q

What are some drug interactions associated with bupivacaine?

A

Patients taking MAOIs or TCAs may produce severe, prolonged hypertension

Concurrent use of these agents should generally be avoided and careful patient monitoring is essential

23
Q

What are the 2 agents discussed in class that affect vesicular acetylcholine release?

A

Botulinum toxin

Tetanus toxin

24
Q

What produces botulinum toxin?

A

Clostridium botulinum, a gram-positive anaerobic bacteria

25
The clinical syndrome of botulism can occur following ingestion of contaminated food. What is its mechanism of action?
BTX prevents the release of acetylcholine from axon endings at the NMJ and thus causes flaccid paralysis [BTX is endocytosed, its light chain cleaves specific SNARE proteins necessary for ACh vesicle to fuse with membrane, so it cannot be released]
26
What makes botulism toxin a good weapon?
Extreme potency and lethality Ease of production Difficult to distinguish intential exposures Expensive, long-term care needed for recovery
27
What produces tetanus toxin?
Tetanus toxin is an extremely potent neurotoxin produced by the vegetative cell of Clostridium tetani in anaerobic conditions, causing tetanus
28
Tetanus toxin is the neurotoxin that causes ________; it travels through nerve cells to the ____ ______ and causes severe muscle cramps
Lockjaw Spinal cord
29
_______ _______ are non-depolarizing agents that compete with acetylcholine, a chemical that carries info between nerve and muscle cells, and blocks transmission of that information
Curare alkaloids
30
___________ is a competitive, non-depolarizing blocking agent that is 5x more potent than tubocurarine but with reduced histamine release as well as a lack of ganglionic blockade
Pancuronium
31
________ is a competitive, non-depolarizing blocking agent that also has some muscarinic blocking activity
Gallamine
32
_________ is a competitive non-depolarizing blocking agent that is short-acting and undergoes hydrolysis by acetylcholinesterase
Mivacurium
33
_________ is a competitive non-depolarizing blocking agent other than Mivacurium that undergoes hydrolysis by AChE
Atracurium
34
What drug acts as a depolarizing muscle relaxant and may be used to induce anesthesia or when a tube must be inserted in the trachea?
Succinylcholine
35
What is the mechanism of action of succinylcholine?
Affects depolarization; keeps muscles from contracting, leading to paralysis of muscles of the face and those used to breathe and move
36
Succinylcholine keeps muscles from contracting, leading to paralysis of muscles of the face and those used to breathe and move. What are some adverse effects associated with succinylcholine?
``` Postoperative pain Jaw rigidity Excessive salivation Hypotension Rash ``` [there are also many drugs known to interact with succinylcholine; risk of acute rhabdomyolosis with hyperkalemia followed by ventricular arrhythmias, cardiac arrest, and death in those found to have undiagnosed muscle myopathies like DMD]
37
What are the clinical uses for agents that inhibit acetylcholinesterase?
Dementia associated with Alzheimer or Parkinson's Myasthenia gravis Nerve gas and organophosphate pesticide exposure Reversal of neuromuscular blockade during anesthesia
38
What are some agents known to inhibit acetylcholinesterase?
Short acting (alcohol): edrophonium Intermediate acting (carbamates): Neostigmine, pyridostigmine, physostigmine Long acting (organophosphates): echothiophate, malathion, parathion, sarin
39
What agent is used in the treatment of severe high body temperature (malignant hyperthermia), and clinical spasticity resulting from upper motor neuron disorders like spinal cord injury, stroke, cerebral palsy, or MS?
Dantrolene (aka Dantrium or Revonto)
40
Dantrolene is an agent characterized by its ability to affect muscle contraction. What is its mechanism of action?
Muscle relaxant - restores a normal level of calcium in the muscles which helps to prevent or reduce severe high body temperature
41
Dantrolene is a muscle relaxant that restores a normal level of calcium in the muscles which helps to prevent or reduce severe high body temperature. What are some adverse effects associated with Dantrolene?
Drowsiness, bloody/black tarry stool, dark urine, confusion, constipation [many drugs are known to interact with Dantrolene as well]