L13: SA Neuromuscular Blocking Agenst (Granone)

Question 1

NMJ

Answer 1

Interface b/w large myelinated nerve fiber and muscle that innervates it

Composed of pre-jx motor nerve ending, synaptic cleft filled with ECF, and membrane of post-jx skeletal m. Fiber

Ach goes across cleft

Question 2

Physiology of the NMJ

Answer 2

• nicotinic cholinergic receptors lie on pre and post-junctional areas of the NMJ, which bind Ach
• synthesis and mobilization of Ach from pre-junctional neuron
• resting transmembrane potential -90 mV due to unequal distr. of K and Na

Question 3

Extrajunctional vs. junctional post-synaptic receptors

Answer 3

Junctional: end plates of normal adult animals; interact w/ Ach resulting in m. Contraction

Extrajunctional: synthesized w/ less than normal nerve stimulation; increased after spinal cord injury or muscle disuse

Question 4

NM transmission summary

Answer 4

1) muscle cells depolarized by end-plate potential –> m. Contraction
- potential cause by binding of Ach to receptor

2) M. Cells repolarized as Ach removed from receptor by AchE
- Ach hydrolyzed and repackaged
- m. Relaxes

Question 5

Ach binding is competitive and reversible

Answer 5

2 Ach must bind to each alpha subunit receptor to have an effect

A NM antagonist must only bind to 2 subunit to prevent normal fx

Question 6

NM transmission dependent on:

Answer 6

Conc. Of Ach vs. concentration of antagonist

Question 7

NMB agent MOA

Answer 7

Competitive binding of Ach receptor

-can be polarizing (ie. Atracurium) or depolarizing (succinylcholine)

Question 8

Depolarizing NMB agents and MOA

Answer 8

• competitively bind to receptor like Ach and stimulates it
• causes depolarization of post-jx membrane
• NOT degraded by AchE, so repolarization doesn’t repolarize
• causes inexcitability and flaccid paralysis
• ie: succinylcholine

Question 9

Nondepolarizing NMB agents and MOA

Answer 9

• bind to Ach receptor but don’t activate it
• causes progressive m. Weakness –> flaccid paralysis
• Atracurium, pancuronium, rocuronium, vecuronium

Question 10

Properties of atracurium

Answer 10

• short-acting nondepolarizing NMB drug
• DOA 20-30 min
• few CV effects
• eliminated by Hoffman elimination (spontaneous molecular degradation that is pH and temp. Dependent)
• can cause HA release –> hypotension

Question 11

Properties of Pancuronium

Answer 11

Long-acting nondepolarizing NMB drug

• DOA 40-60 mins
• excreted by kidneys, met. By LIV
• Vagolytic effect: inhibits cardiac muscarinic receptors –> tachycardia

Question 12

Uses of NMB drugs

Answer 12

• ophtho sx
• dec. resistance to controlled ventilation
• facilitate sx access

Question 13

Order of paralysis

Answer 13

1) muscles of face, jaw, tail
2) neck, distal limbs
3) proximal limbs
4) pharynx, larynx
5) abdomen
6) intercostal muscles
7) diaphragm

Question 14

Monitoring while using NMB drugs

Answer 14

• PPV
• Peripheral n. Stim.
• reversal agent
• watch for signs of full blockade: loss of jaw tone, pedal withdrawal, palpebral, central eye, apnea
• ensure good plane of anesthesia b/c p may not be able to move if light

Question 15

Peripheral nerve stimulator

Answer 15

• monitors evoked motor response
• degree of NM blockade
• applied to peripheral motor nn.
• presence of NMB agent –> absence of movement
• TOF most often used

Question 16

Normal T4:T1 ratio

Answer 16

1.0

Question 17

What percent of receptors need to be occupied before twitches start to fade? In what order? ***

Answer 17

70%

1) T4
2) T3
3) T2
4) T1

Will return in reverse order as drug wears off

Question 18

Blockade reversal

Answer 18

1) Normal: AchE (hydrolyzes ACh)

2) AchE inhibitors
-increase ACh concentration, which take place of NMB drug at receptor
-indirectly restores NM transmission
Drugs: Edrophonium, Neostigmine, Pyridostigmine

Question 19

ACh is the NT at which receptors?

Answer 19

Nicotinic and muscarinic receptors

-sinus node, smooth muscle, glands, skeletal and cardiac m.

Question 20

Increased Ach at muscarinic receptors –>

Answer 20

Bradycardia
Sinus arrest
Bronchospasm
Miosis
Inc. intestinal peristalsis
Salivation

Question 21

Prevention of muscarinic stimulation effects

Answer 21

• administer anticholinergic (antimuscarinic) prior to NMB reversal
• blocks muscarinic receptors
• causes inc. HR, bronchodilation, dec. GI peristalsis

Question 22

NMB drug action must wane before antagonism with reversal agent - why?**

Answer 22

• premature reversal –> blockade refractory to reversal
• 3 twitches of TOF should be present first
• depolarizing NMB drugs cannot be reversed!!

Question 23

Neuromuscular blocking drugs are peripheral muscle relaxants. MOA:

Answer 23

-interfere w/ NM transmission

• anesthetic adjunct only
• lack sedative, hypnotic, analgesic, amnestic properties