Drugs acting on the neuromuscular junction PNS (somatic)

Question 1

Which of the following are other pharmacological effects from using depolarizing neuromuscular blockers? (choose all that apply)

1. Hyperkalemia due to K+ release from skeletal muscles
2. Increased intraoccular pressure due to contraction of ocular muscles
3. Hypercalcemia from the buildup of Ca+ in the ER
4. Transient bradycardia, increased susceptibility of the heart to the actions of digitalis preparations
5. Nicotinic ACh receptors at autonomic ganglia (less sensitive than at the neuromuscular junction)

Answer 1

1. Hyperkalemia due to K+ release from skeletal muscles
2. Increased intraoccular pressure due to contraction of ocular muscles
3. NOPE NO NOPE NOPE WRONG NOPE NO NO NOPE
4. Transient bradycardia, increased susceptibility of the heart to the actions of digitalis preparations
5. Nicotinic ACh receptors at autonomic ganglia (less sensitive than at the neuromuscular junction)

Question 1

Summative or synergistic drug interactions of competitive NM blockers with which of the following can be seen? (choose all that apply)

1. Other muscle relaxants
2. Local anesthetics
3. Inhalation anesthetics
4. Aminoglycosides
5. Magnesium
6. Calcium
7. Potassium

Answer 1

1. Other muscle relaxants
2. Local anesthetics
3. Inhalation anesthetics
4. Aminoglycosides
5. Magnesium

Question 2

Is this describing phase 1 or phase 2 block of Succinylcholine, a depolarizing neuromuscular blocker?: Activation of nicotinic ACh receptors (like acetylcholine), induces prolonged depolarization of the motor end-plate, no complete repolarization prevents stimulation by ACh (depolarization block), and muscle fasciculation.

1. Phase 1
2. Phase 2 block

Answer 2

1. Phase 1

Question 2

Depolarizing neuromuscular blockers are hydrolyzed by plasma _________________________-ase in the ____________ and _____________.

Answer 2

Pseudocholinesterase (PChE) in the plasma and liver (it is slower than acetylcholinesterase [AChE])

Question 2

This nondepolarizing/competitive neuromuscular blocker is mostly excreted and unchanged by the kidneys (~40% in humans), has some liver metabolism, and has little excretion in bile.

1. Pancuronium
2. Atracurium
3. Vecuronium
4. Mivacurium
5. Rocuronium

Answer 2

1. Pancuronium

(good for patients with decreased liver function)

Question 2

This nondepolarizing/competitive neuromuscular blocker has spontaneous degradation in the plasma (outside of the liver and kidney).

1. Pancuronium
2. Atracurium
3. Vecuronium
4. Mivacurium
5. Rocuronium

Answer 2

2. Atracurium

(better for patients with liver and renal disfunction)

Question 3

T or F. Neuromuscular blockers were developed from dart poisons.

Answer 3

True

Question 5

T or F. Neuromusclar blockers are peripheral muscle relaxants that paralyze all skeletal muscles, except the muscles associated with respiration.

Answer 5

False! They paralyze ALL skeletal muscles, even the intercostal muscles and the diaphragm. Assisted ventilation is required!

Question 6

The motor neurons of the somatic nervous system release _______________, which work on _______________ receptors.

1. ACh, adrenergic
2. ACh, muscarinic
3. ACh, nicotinic
4. NE, adrenergic

Answer 6

3. ACh, nicotinic

Question 7

T or F. Depolarizing and competitive neuromuscular blockers work on the postsynaptic neuromuscular junction.

Answer 7

True (nicotinic receptors)

Question 7

T or F. Nondepolarizing neuromuscular blockers can cause flaccid muscle paralysis, hypotension, and bradycardia.

Answer 7

False! Bradycardia is caused by depolarizing NMB.

Nondepolarizing neuromuscular blockers can cause flaccid muscle paralysis, mild hypotension from ganglionic blockade (nicotinic receptors at autonomic ganglia are less sensitive than those at NMJ), and transient TACHYCARDIA (not in anesthetized animals).

*REMEMBER, NO MUSCLE FASCICULATION (TWITCHING) unlike Succynlcholine (depolarizing NMB), which can be a good thing*

Question 8

T or F. Depolarizing neuromuscular blockers cause transient, asynchronous muscle twitching (30 seconds) followed by flaccid paralysis and can be very painful (increase in creatine kinase).

Answer 8

True

Question 9

T or F. Patients on neuromuscular blockers are unconcious and are under full analgesia.

Answer 9

False, consciousness is not affected. The patient is still fully conscious, under NO ANALGESIA, and is just paralyzed.

Question 10

T or F. Muscle relaxants such as Hemicholinium, Vesamicol, Botulinum toxin, high Mg++, and low Ca++, work on the postsynaptic neuromuscular junction to interfere with synthesis, transport/storage and/or release of acetylcholine.

Answer 10

False; muscle relaxants (Hemicholinium, Vesamicol, Botulinum toxin, high Mg++, and low Ca++) work on the PREsynaptic neuromuscular junction to interfere with synthesis, transport/storage and/or release of acetylcholine.

(not really used in VetMed)

Question 11

MATCHING! Which drugs are depolarizing (noncompetitive) or competitive neuromuscular blockers?

A. Depolarizing (noncompetitive)

B. Competitive

1. Rocuronium
2. Mivacurium
3. Vecuronium
4. Atracurium
5. Succinylcholine
6. Pancuronium

Answer 11

A. Depolarizing (noncompetitive) - 5. Succinylcholine (ONLY ONE)

B. Competitive - 1. Rocuronium, 2. Mivacurium, 3. Vecuronium, 4. Atracurium, 6. Pancuronium

(Competitive = Vec Pan Roc At Mi, imagine “Vik is competitive so she’s running with a pan and rock at me”)

Question 13

Neuromuscular blockers are ALL quaternary compounds. What is characteristic about them?

Answer 13

• Always charged
• Poor oral absorption
• Usually given IV
• Do not cross BBB

Question 14

T or F. Succinylcholine is used as an adjunct to euthanasia.

Answer 14

False! How awful would it be to be fully conscious during this.

Question 15

These two nondepolarizing/competitive neuromuscular blockers are primarily metabolized by the liver and excreted in bile and urine.

1. Pancuronium
2. Atracurium
3. Vecuronium
4. Mivacurium
5. Rocuronium

Answer 15

3. Vecuronium and 5. Rocuronium

(better for patients with renal disfunction)

Question 16

T or F. Depolarizing neuromusclar blockers are given orally.

Answer 16

False, IV and rarely IM

(they have very poor oral absorption, aso want tight control)

Question 17

Put the affected areas in order (first to last) from depolarizing neuromuscular blockers.

1. Swallowing
2. Respiratory
3. Abdominal muscles
4. Limbs
5. Tail/face

Answer 17

5. Tail/face > 4. limbs > 1. swallowing / 3. abdomial muscles > 2. respiratory (most important one!)

Question 18

All of the following are adverse effects of Succinylcholine, except:

1. Bradycardia
2. Hyperkalemia
3. Hypercalcemia
4. Muscle fiber damage, increased CK, muscle pain post-op
5. Apnea
6. Increased arrhythmogenicity to catecholamines
7. Malignant hyperthermia in susceptible animals

Answer 18

3. Hypercalcemia

Question 19

T or F. Succinylcholine is used to facilitate endotracheal intubation.

Answer 19

True

Question 21

CAUTION! Which of the following are not cautions for using nondepolarizing blockers?

1. Caution with liver or kidney disease (consider Atracurium in those cases)
2. Bronchospasm
3. Bronchodilation
4. Salivation
5. Bronchial secretion
6. May cause histamine release in dogs/cats (much less so than with tubocurare)

Answer 21

3. Bronchodilation

Question 22

This nondepolarizing/competitive neuromuscular blocker is easily terminated by chelation with cyclodextrins, such as sugammadex and has a very fast onset of action.

1. Pancuronium
2. Atracurium
3. Vecuronium
4. Mivacurium
5. Rocuronium

Answer 22

5. Rocuronium (not used in Vet Med as much, but it is up and coming)
   * Sugammadex* is a reversal agent that takes and removes the drug itself = tight control

Question 24

T or F. Depolarizing neuromuscular blockers (Succynlcholine) have a very short duration of action at around 2-3 minutes.

Answer 24

**True**, EXCEPT longer in _ruminants_ and _dogs_ (20 minutes); acts in one circulation time of 30-60 seconds

Question 25

T or F. Nondepolarizing/competitive blockers are given IV (rarely IM), just like depolarizing neuromuscular blockers.

Answer 25

True

Question 26

Curare is a ______________ neuromuscular blocker. 1. Depolarizing 2. Competitive

Answer 26

2. Competitve; just like Pancuronium, Atracurium, Vecuronium, Mivacurium, Rocuronium ## Footnote *[Vik (_Vec_) is competitive so she came _At_ _Mi_ with a _Pan_ and _Roc]_*

Question 27

Is this describing phase 1 or phase 2 block of Succinylcholine, a depolarizing neuromuscular blocker: Nicotinic ACh receptors do not respond properly to ACh and flaccid paralysis is prolonged. We want to avoid this. 1. Phase 1 2. Phase 2 block

Answer 27

2. Phase 2 block

Question 28

Which competitive (nondepolarizing) neuromuscular blockers should _not_ be used? 1. Pancuronium (Pavulon) 2. Mivacurium 3. Fazadinium 4. Rocuronium (Esmeron) 5. Pipercuronium 6. Tubocurarine 7. Atracurium (Tracrium) 8. Vecuronium (Nocuron) 9. Gallamine 10. Alcuronium

Answer 28

Whichever one is not "*_Vec_ came _At_ _Mi_ with a _Pan_ and _Roc_*" 3. Fazadinium 5. Pipercuronium 6. Tubocurarine 9. Gallamine 10. Alcuronium

Question 30

T or F. Succinylcholine is used as a muscle relaxant during surgery.

Answer 30

True, but rarely.

Question 31

CAUTION! All of the following are cautions for Succinylcholine (depolarizing NMB), _except_: 1. Cholinesterase inhibitors, aminoglycosides, other muscle relaxants, digitalis, magnesium 2. Keep at room temperature so no precipitates form 3. Glaucoma 4. Cardiac disease 5. Keep refrigerated or on ice to avoid spontaneous hydrolysis of the drug

Answer 31

2. Keep at room temperature so no precipitates form

Question 32

What happens if Succinylcholine was given, but you want to reverse the effects?

Answer 32

**There is no specific reversal**, so supportive care (ventilation) is needed until the drug is metabolized. Anything that alters metabolism will _prolong_ the effect (exposure to irreversible cholinesterase inhibiters, such as organophosphates, can slow hydrolysis of depolarizing neuromuscular blockers for *up to 30 days!*)

Question 33

What happens when competitive NM blockers are given, but you want to reverse its effects?

Answer 33

* **Respiratory support** *(like depolarizing blockers)* * **_Cholinesterase inhibitors_** to anatagonize the effect of nondepolarizing NMBs (neostigmine, edrophonium have reverse drug interactions) * *​*Cholinesterase inhibitors \> less break down of ACh \> more ACh in the NMJ \> more muscle function * Atropine/Glycopyrrolate to block muscarinic effects (NOT IN HORSES = COLIC)

Question 34

Competitive neuromuscular blockers work by competitive _______________ with acetylcholine for _______________ receptors at the motor end-plates. 1. Antagonism, nicotinic 2. Antagonism, muscarinic 3. Agonism, nicotinic 4. Agonism, muscarinic

Answer 34

1. Antagonism, nicotinic ## Footnote *(they BLOCK nicotinic receptors and don't allow ACh to bind, so **no initial muscle fasciculation (twitch) stage**, just muscle paralysis; kind of like a medical myasthenia gravis)*