L4

Question 1

What are the uses of neuromuscular blockers?

Answer 1

Muscle relaxants - intubation, surgery
Muscle paralysis - botox
Ortho

Question 2

Describe the structure of the NMJ

Answer 2

Pre-synapse w/ active zones
Basal lamina w/ AChE
Post-synapse w/ dense nAChR
Peri-jxnal Na+ channels deep in synaptic folds

Question 3

What are the 2 forms of botulinum toxin?

Answer 3

Both work to disrupt the SNARE proteins for vesicle fusion to release ACh at NMJ
BoNT A = botox, cleaves SNAP 25
BoNT B = myobloc, cleaves synaptobrevin

Question 4

4 clinical uses of botulinum toxins

Answer 4

1. Strabismus = misaligned eyes
2. Excessive sweating
3. Cervical dystonia (head twisting)
4. Cosmetic

Question 5

What is the structure of AChR?

Answer 5

Ion channel - Na/K
5 subunits: 2 alpha, beta, delta, gamma or epsilon (development)
ACh binds alpha subunit - need 2 AChs
Therefore blockers that bind 1 alpha inactivate the entire receptor

Question 6

5 non-depol NM blockers

Answer 6

1. d-Tubocurarine
2. Pancuronium
3. Vecuronium
4. Cisatracurium
5. Rocuronium

Question 7

1 depolarizing NM blocker & metabolism

Answer 7

Succinyl choline

Hydrolyzed (aka metabolized) by BChE

Question 8

Mechanism of non-depol NM blockers

Answer 8

Works by competitively blocking nAChR
See:
- ↓mepp & epp - proportionally

Question 9

Why are non-depol NM blockers competitive blockers?

Answer 9

With repeated stimulation, see temporal summation

- ↑ACh in synapse yields larger and large depol - adds with each release to eventually reach threshold

Question 10

Mechanism of depol NM blockers

Answer 10

Na channel inactivation
Binds nAChR - causing depol - then inactivates it
- Add drug slowly to suppress initial depol from happening all at once
If stim nerve, still get epps but don’t reach threshold b/c not opening any channels

Question 11

What is the train of 4 stimulation

Answer 11

Tests depth of NM block

Fade = muscle twitch starts high then fades in correlation to the degree to which the non-depol is blocking

Question 12

What does recovery from an NM block look like?

Answer 12

Looks like a train of 4
Starts high - goes low
See net amplitude grow with recovery until all twitches return to same baseline amplitude

Question 13

NM blocker toxicity - what are 3 things you’re worried about

Answer 13

1. Breathing - toxic level will arrest diaphragm muscle too
2. Stimulating histamine release
3. Inducing malignant hyperthermia

Question 14

Can NM blockers cross BBB?

Answer 14

No - all charged
Also why can’t give PO - poor tissue penetration
Give IV

Question 15

Babies response to NM blockers

Answer 15

More sen to ND blockers (use less)
Less sen D
B/c of how NMJ matures

Question 16

Hypothermic response to NM blockers

Answer 16

Less sen to ND blocker
More sen to D
Lower temp = less efficient ATPase = membrane potential is more positive than normal (closer to threshold)

Question 17

Genetic variant that would dictate NM blocker response

Answer 17

BChE variants for succinylcholine metabolism

Question 18

Which electrolytes should you be aware of affecting the NMJ/NM blockers?

Answer 18

Ca2+

K

Question 19

Hypokalemia response to NM blockers

Answer 19

Hyperpolarized
More sen to ND
Less sen to D

Question 20

Hyperkalemia response to NM blocker

Answer 20

Closer to threshold
Less sen to ND
More sen to D

Question 21

Which pts might be hypovolemic? How does this effect NM blockers?

Answer 21

Burn & trauma
Artificial hyperkalemia
DON’T use succinylcholine

Question 22

How do MG pts respond to NM blockers?

Answer 22

Fewer nAChR there b/c autoimmune attack
BUT whatever is there is hypersensitized
VERY sen to ND blockers (acts directly on receptor)

Question 23

How do pts with small cell (bronchiogenic) carcinoma respond to NM blockers?

Answer 23

No Ca2+ channels on pre-synaptic side
Less vesicle fusion –> less ACh release
Sen to BOTH ND and D

Question 24

How do pts with liver disease respond to NM blockers? Which 3 NM blocker are specifically effected?

Answer 24

Liver makes less BChE

Decrease SuCh, vecuronium, rocuronium metab

Question 25

What is malignant hyperthermia?

Answer 25

@ muscle: rapid release SR Ca2+ for no reason

Heat production via ATP - rapid rise body temp

Question 26

Which NM blocker can induce underlying malignant hyperthermia?

Answer 26

SuCh

Question 27

What is the difference between neurotransmission at the NMJ vs ganglia

Answer 27

NMJ = 1:1
Ganglia = temporal & spatial summation

Question 28

Which receptors create fast EPSP

Answer 28

nAChR

Question 29

Which receptors create slow IPSPs

Answer 29

mAChR

Question 30

2 ganglionic blocking agents

Answer 30

Mecamylamine

Trimethaphan

Question 31

What happens with ganglionic blockade?

Answer 31

Reverse the dominant autonomic tone of that organ - opposite of normal baseline
Ex: heart becomes tachycardic w/ ↑CO (baseline = para)