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