NMJ Pharm

Question 1

Function of botulinum toxin

Answer 1

lyses synaptobrevin

decr synaptic fusion and release of ACh

Question 2

function of black widow spider venom

Answer 2

excessive clumping of ACh vesicles –> explosive release of NT

Question 3

Brief stim of nicotinic cholinergic recpeotrs

Answer 3

conductance of cations (mostly Na) thru channel –> depol –> if reach trheshold, AP –> contraction

opens inactiv gates of VG Na+

Question 4

Prolonged stim of nicotinic cholinergic recpeotrs

Answer 4

membrane can’t repol and inactivation gates don’t reopen

VG Na channels don’t conduct sodium –> AP can’t be fired again

nAChR becomes desensitized so uncoupled ACh binding

Question 5

what does desensitization of nAChR mean?

Answer 5

still binds ACh but does not couple to open of ion channel so no AP

Question 6

antagonists for nAChRs at the NMJ do what?

which muscles affected first?
what about at high concentration

Answer 6

competitively bind receptor
prevent ACh from binding and no depol
–> inhib muscle contraction

muscles receiving greatest innerv (white fast twitch muscles”
at higher concentrations –> red “slow muscles”

Question 7

effect of nAChR antagonist on analgesia and anesthesia

Answer 7

none

Question 8

NMJ nAChR antag used clinically as what?

drug abs in GI tract?
how to administer

Answer 8

surgical anesth to relax skeletal muscles and facilitate intub by relax airway muscles

not abs in GI tract
administer IV

Question 9

Effect of curare, atracurium, rocuronium

Answer 9

competitive nAChR antag at NMJ

Question 10

curare side effect

effect of curare at high [ ]

Answer 10

histamine release –> side effect of hypotension

high [ ] = inhib neuronal nAChR and ganglionic neurotranmission

Question 11

compare onset, duration of curare, atracurium, rocuronium

Answer 11

curare onset = 4-6 min
atracurium onset = 2-4 min
rocuronium onset = 1-2 min

duration
80-120 min
30-60
30-60

Question 12

elim of curare, atracurium, rocuronium

Answer 12

kidney
spntaneous hydroysis and plasma ChE
liver

Question 13

ganglionic nAChR inhib of curare, atracurium, rocuronium

histamine release for curare, atracurium, rocuronium?

Answer 13

ganglionic nAChR
yes
no
no

histamine release
yes
some
no

Question 14

what makes succinylcholine distinct from other clinically used neuromusc blocking agents

Answer 14

succinylcholine = depol blocker while others are competitive antag

succinylcholine blocks depol by first interact with nAChR and cause burst of AP –> fasciculations

Question 15

describe phase 1 block of succinylcholine

Answer 15

not rapidly elim from NMJ –> sustained depol –> depol block –> desensitization of nAChR and flaccid paralysis

Question 16

describe phase 2 block of succinyclholine

Answer 16

after phase 1, curare-like competitive block remains

Question 17

useful clinically of succinylcholine?

Answer 17

duration = 8 min so titrated on min to min basis

Question 18

effect of succinylcholine on K+

how is it degraded?

Answer 18

causes hyperkalemia (release of K+ during block)

degraded by plasma ChE

Question 19

effect of AChE inhib on nondepol vs depol neuromusc blocking agents

Answer 19

AChE inhib incr ACh at NMJ and inhib neuromusc block prod by competitive “curare-like” nAChR antag

but AChE inhib add to depol block by succinylcholine –> causing phase 1 block

Question 20

effect of drugs that decr ACh on nondepol vs depol neuromusc blocking agents

Answer 20

enhance competitive “curare-like” nAChR antag

include antibiotics that compete for calcium req’d for ACh release presynap and opioid analgesis that decr ACh rel by activating presynaptic opioid receptors