Kruisin' with Kruse

Question 1

Pt presents with exertional weakness and fatigue of the facial muscles. PE sign. for eyelid ptosis.

1. Antibodies to what enzyme or reeptor at the NMJ would most likely cause his sx?
2. What is the likely diagnosis?
3. How could we use pharmocologic agents to treat this condition?
4. what is the enzyme targeted by the drug?
5. What adverse effects would you expect from this drug?
6. Do we want the drug to becharged or uncharged?

Answer 1

1. Nicotinic acetylcholine receptor
2. Myasthenia Gravis
3. Inhibitor of acetylcholine esterase to increase the amount of Ach in the synapse in an attempt to increase the competiton of Ach so that muscle contraction can occur as appropriate.
4. Acetylcholine esterase
5. Increasing acetylcholine for muscarinic receptors in smooth and cardiac muscle (increase parasympathetic activity, thus diarrhea, bradycardia (rest and digest stuff))
6. Charged because it will stay in the PNS and not cross the blood brain barrier, so you get less CNS/systemic effects. Uncharged would cross the blood rbain barrier/lipid bilayer which is good if we need to treat the brain, but we aren’t trying to treat the brain now.

Question 2

Botox (TM) and other botulinum toxin based drugs/toxins inhibit what?

Answer 2

VAMPs and SNAPs (SNARE Complex) which leads to NO Ach releasing from the presynaptic membrane.

Causes Flaccid Paralysis (i think)

Question 3

Malignant hyperthermia case

Prepping for surgery

1-2. Why do we give succinylcholine for paralysis instead of Ach esterase inhibitor?

3. How does Succinylcholine work?
4. compare succ. to d-turbocurarine

Answer 3

1. Ach esterase inhibitor can cause fasiculations and paralysis, but it gets broken fown in miliseconds, so it would never be used, especially in high doses. Sometimes used in chemical warfare.
2. Succinylcholine is used instead because it breaks down in seconds (3-5min, really) so it lasts long enough for necessary clinical interventions)
3. as an agonist, stimulating receptor for body’s natural response.
4. d-turbocurarinie does the same thing as succ. but as an antagonist, blocking Ach. receptor. Really long lasting and hard to manage, so not used.

Question 4

MAlignant hyperthermia case

Malg. Hyper. part

1. Why is pt’s CO2 high?
2. What in the stem indicates a malginant hyperthermia?
3. What is a common side issue if MH is not dealt with quickly?
4. Why does MH even happen?
5. How do we fix it?

Answer 4

1. Body temp increases, increases muscle contraction, increases metabolism, causing acidosis and increase in CO2. Ventilator is not compensating for this and her body temp is increasing!
2. A dramatic (.5’C) increase in temp in 15min. Malig. Hyper. typically becomes evident in the first 15-30min after succ. is given. Evident that this is not a succ. overdose since the pt was started with succ and then transferred to another med (vercuronium) when sx. started.
3. High temp digests muscles which go to kidney and damage kidney causing Rhabdomyelisis which can cause kidney failure
4. genetic issue in the RyR or DHP becayse the Ca cannot be sequestered, so lingering Ca allows muscles to continually contract, increasing body temp.
5. Dantrolene, cooling. Dantrolene helps RyR sequester CA. Also remove all sources of succ. an place on 100% O2.

Question 5

Pt presents with blurry vision, dry mouth, diff swallowing and speaking, vomiting and diarrhea

She had homemade canned goods

Whats the problem?

Answer 5

Botulinum toxin

Won’t be Achesterase inhibitor because although that would increase her parasym. (diarrhea) yuo would also see Skeletal Muscle sx. None here.

Won’t be d-Turocurarine because that only has skeletal muscle sx, no GI sx.

Won’t be tetanys since that would cause tetany.

Won’t be Tetrodotoxin because its from puffer fish and she would have severe diff. breathing and maybe death

Question 6

What blocks axonal conduction?

Answer 6

Tetrodotoxin

local anesthetics (Na+ channels)

Question 7

What blocks release of the NTMs from the vesicles?

Answer 7

Botulinum toxin (GI sx, resp. issues)

tetanus toxin (Tetany)

Question 8

Ach inhibitor acts where?

Answer 8

at the Ach esterase thing

Question 9

What blocks the receptors on the target cell?

Answer 9

Curare

Succinylcholine

Question 10

What block Ca+ in muscle?

Answer 10

Dantrolene (malig. hyperterhmia tx)

Question 11

Curare alkaloids cause

Answer 11

flaccid paralysis

no fasiculations

act as antagonist at the nicotinic receptor

reverse with Ach

Question 12

Succinylcholine causes

Answer 12

spastic paralysis

with fasiculatinso and then paralysis

acts as an agonist to the receptor

time reversis (3-5min)