NMJ Pharmacology

Question 1

Voltage-sensitive sodium channels (VSSCs) can be blocked by ___

Answer 1

local anesthetics (lidocaine)

Question 2

Synaptobrevin is lysed by ___ at the NMJ preventing vesicle fusion and thus ACh release, producing a flaccid paralysis of skeletal muscle

Answer 2

botulinum toxin

Question 3

Both botulinum toxin and black widow spider venom cause death by ___

Answer 3

respiratory failure

Question 4

Black widow spider toxin (alpha-latrotoxin) forms pores in terminal membranes allowing ___ which causes ___

Answer 4

excessive Ca++ influx, clumping of vesicles, and explosive release of ACh

Question 5

Tetanus toxin cleaves ___ in the CNS to block release of GABA and other inhibitory NTs, causing spastic paralysis

Answer 5

synaptobrevin II

Question 6

Botulinum toxin produces ___ paralysis; tetanus toxin produces ___ paralysis. They both cleave synaptobrevin, tetanus does so in the ___

Answer 6

flaccid, spastic, CNS

Question 7

___ is a competitive antagonist of the Nm receptor, preventing depolarization and producing flaccid paralysis

Answer 7

Curare alkaloids

Question 8

___ is an agonist of the Nm receptor, ultimately causing depolarization blockade, producing flaccid paralysis

Answer 8

Succinylcholine

Question 9

___ is an inhibitor of cholinesterase at the NMJ, increasing ACh binding to receptor and causing increased strength and depolarization block at higher dose

Answer 9

Neostigmine

Question 10

Examples of curare alkaloids include ___ (isoquinolone structural class) and ___ (steroid structural class), both reversily block Nm receptors

Answer 10

atracurium, rocuronium

Notice the “curium” and “curonium” it’s how to differentiate

Question 11

You can overcome curare effects with ___

Answer 11

cholinesterase inhibitors, to increase ACh at the junction

Question 12

___ is literally just 2 ACh molecules joined together

Answer 12

Succinylcholine

Question 13

Succinylcholine acts by ___, the difference from it and ACh is that ___

Answer 13

binding Nm receptors; it’s not hydrolyzed by AChe

Question 14

Succinylcholine is terminated by ___

Answer 14

diffusion from synapse and degradation by butyrylcholinesterase

Question 15

Succinylcholine is hydrolyzed by ___

Answer 15

pseudocholinesterase (butyrylcholinesterase), bitch

Question 16

Butyrylcholinesterase preferentially hydrolyzes ___ esters such as succinylcholine

Answer 16

longer chain

Question 17

At the catalytic site of ACHe, the acetyl group is covalently bound to the ___ group while choline gets released

Answer 17

serine (Ser-OH)

Question 18

The anionic site attracts the ___ group of choline via ionic forces

Answer 18

quaternary (+)

Question 19

___ is a reversible, short acting AChe inhibitor that binds ionically only to the anionic site

Answer 19

Edrophonium, Ambenonium is slightly longer acting

Question 20

Neostigmine is reversible and ___ acting

Answer 20

intermediate-long

Question 21

___ is the version of neostigmine which crosses the BBB

Answer 21

Physostigmine

Question 22

Echothophate is ___ inhibitor of AChe used to treat glaucoma

Answer 22

irreversible

Question 23

The mainstay of treatment for myasthenia gravis is now ___

Answer 23

immunotherapies, with cholinesterase inhibitors as adjunctive therapy

Question 24

BB SLUDGE is for ___ receptor signs, and stands for

Answer 24

muscarinic receptors

Bradycardia
Bronchoconstriction

Salivation
Lacrimation
Urination
Defection
GI effects, emesis
Eye (miosis)

Question 25

MATCH is for ___ receptor signs, and stands for

Answer 25

nicotinic receptors ``` Muscle weakness/fasciculations (Nm) Adrenal medulla activity increases (Nn) Tachycardia (Nn) Cramping of SkM (Nm) Hypertension (Nn) ```

Question 26

SLUDGE treatment, or how to treat excessive parasympathetic effects

Answer 26

Atropine

Question 27

___ is an oxime derivative used to treat completely inactivity of cholinesterase

Answer 27

Pralidoxime