NMJ blockers

Question 1

Atracurium (Tracrium®)

Answer 1

non-depolarizing NMJ blocker
Benzylisoquinolines
Time to onset of action 2-4 min
-degraded by temp/pH-dependent Hofmann reaction.
-not metabolized by enzymes and may be useful for patients with liver and/or renal failure.

Question 2

Mivacurium (Mivacron®)

Answer 2

non-depolarizing NMJ blocker
Short duration of action (12-18 min)
Benzylisoquinoline, Time to onset of action: 2-4 min
metabolized by plasma
cholinesterase (why short duration)
-Problems if given when decreased plasma cholinesterase activity
Pts with liver disease or nutritional deficiencies may have abnormal plasma cholinesterase activity. Flushing of the face and neck is common.

Question 3

Rocuronium (Zemuron®)

Answer 3

non-depolarizing NMJ blocker
Intermediate Duration of action (30-60 min)
Steroidal structure, Liver metabolism
Time to onset of action: very rapid (1-2 min) similar to succinylcholine and used to rapidly relax laryngeal and jaw muscles for tracheal intubation

Question 4

Succinylcholine (Anectine®)

Answer 4

depolarizing NMJ blocker
Duration (5-8 min); Time to onset; 1-1.5 min – very fast
*Used for very short procedures (e.g. intubation)
*initial fasciculations mostly in the chest and abdomen,
occur immediately after drug admin
-no antidote, (like non-depol NMJ blockers)

Question 5

NMJ blocker uses

Answer 5

GA adjuncts in sx: Cause the complete relaxation of skeletal muscle
-no CNS effects; only given IV

Question 6

1st muscles to be blocked/affected ??

Answer 6

small rapid moving muscles → limb trunk muscles → intercostal muscles → lastly, the diaphragm
*recovery in reverse order, diaphragm is 1st to regain function

Question 7

Botox is used to treat ??

Answer 7

blephorospasm (involuntary eyelid closing), strabismus (eye spasms) and wrinkle treatment

Question 8

Non-depolarizing (competitive) NMJ blockers characteristics

Answer 8

Not metabolized by AChE

• Competitive inhibitors of ACh binding to ACh receptor at NMJ
• antiAChE agents (e.g. neostigmine) reverse NMJ block by non-depolarizing NMJ blockers

Question 9

general non-depolarizing (competitive) NMJ blocker SEs

Answer 9

Prolonged apnea, histamine release (bronchospasm, hypotension)

Question 10

Benzylisoquinonlines ( “___curium” name) SEs

Answer 10

Histamine release, few vagal/ganglionic blocking effects

Question 11

Steroidal compounds (“___curonium” name) SEs

Answer 11

• Block of ganglionic muscarinic receptors can occur resulting in tachycardia due to effects on vagus
• Vecuronium and rocuronium are newer agents with little or no associated tachycardia or histamine release

Question 12

succinylcholine metabolism

Answer 12

Degraded by plasma choline esterase (e.g. butyrylcholinesterase)
Problems with decreased butyrylcholineesterase: atypical or deficient plasma cholinesterase, hepatic or liver disease, nutritional deficiencies

Question 13

succinylcholine MOA

Answer 13

alters electro-chemical driving forces: excessive opening of nicotinic ACh receptors by SCh results in decreased electro- chemical driving forces and therefore less positive ion entry in presence of ACh resulting in less muscle response to motor neuron activity.
-this is phase I: single dose, fast onset; neostigmine augments blocking action of SCh

Question 14

Phase II SCh

Answer 14

after prolonged infusion or dosing 10X of normal dose (5 mg/kg); slow onset

• MP: -80mV
• Neostigmine antagonizes SCh block

Question 15

botulinum toxin

Answer 15

besides wrinkles, for
blephorospasm – involuntary closing of eyelid and strabismus – deviation of eye position that cannot be overcome
MOA: prevent release of presynaptic ACh at NMJ
SEs: upregulation of post-synaptic nicotinic ACh receptors at previous injection site(s) resulting in increased wrinkles and ptosis - eyelid droop