NMDRs

Question 1

NMJ Transmission Function

Answer 1

• ACh synthesized and stored in synaptic veicles
• AP stimulates distal motor nerve
• Ca++ diffuses into terminal and VGCaCh open
• synaptic vesicles fuse to membrane
• ACh released into cleft
• presynaptic nicotinic receptor responds to ACh by synthesizing more and mobilizing ACh vesicles (+ feedback)(phII block w Sux related to this)
• ACh binds to nicotinic ACh receptors on surface of post-synaptic membrane

Question 2

Cholinergic

Answer 2

releases ACh

Question 3

Adrenergic

Answer 3

releases NE

Question 4

Pre/Post Ganglionic NTs

Answer 4

PNS pre and post = ACh

SNS pre = ACh

SNS post = NE

Question 5

ACh is hydrolized by ____ to ____ and _____

Answer 5

ACh is hydrolized by acetylcholinesterase (AChE) to acetate and choline

• choline taken up by presynaptic terminal for resynthesis of ACh
• acetate diffuses away

Question 6

The release of NT is dependent on the entry of Ca++

Answer 6

HYPOcalcemia = decreases NT release (weakness)

HYPERcalcemia = increases NT release (tetany)

HYPOmagnesemia = increases NT release

HYPERmagenesemia = decreases NT release

- the actions of Ca++ and Mg+ are antagonistic at presynaptic nerve terminals

Question 7

ACh receptors - A subunits

Answer 7

both A subunits must be occupied to get contraction! Block one = no contraction. Sux lands on both and we get depolarization

Question 8

Up-regulated AChRs (denervation injuries - burns)

Answer 8

– AChr agonists see increased sensitivity

– AChr antagonists see decreased sensiCvity

• Nondepolarizing muscle relaxants (NDMR) are AChr antagonists

– These patients require increased dosages or shorter redosing intervals of the NMDRs

anesthesia on a burn patient requires frequent redoxing due to upregulation of receptors!

Question 9

Down-regulated AChRs (myasthenia gravis)

Answer 9

– ACHr agonists see decreased sensitivity and require higher dosages

– ACHr antagonists see increased sensitivity and require lower dosages and longer intervals between redosing

our NMDRs are ANTagonists therefore we require higher AGonists

Question 10

Depolarizing Muscle Relaxants (Sux)

Answer 10

• depolarize the nACHr - NOT competitive
• action similar to ACh (ACh depolarizes the NMJ and is rapidly metabolized by AChE)

Question 11

Sux (depolarizing)

Answer 11

• attaches to the 2 A subunits and depolarizes
• metabolized by BCH-esterase (not present in the NMJ)
• after depolarization, sux remains in the synaptic cleft until plasma level lowers and creates a concentration gradient out of the cleft
• after moving out of the cleft, circulating BCH-esterase metabolizes the remaining sux.
• 80-90% of the sux is metabolized in the blood on the way to the NMJ! (so only 10-20% of the dose is giving us action)

Question 12

NON-depolarizing muscle relaxants

Answer 12

• competitive: compete for ACh binding sites on nicotinic receptor
• when bound, it prevents ion channel from opening
• NDMRs completely BLOCK ACh from binding to receptor… post-synaptic membrane remains polarized

Question 13

Non-Depolarized Block

Answer 13

• is from competitive inhibition of nAChR
• shows fade on TOF monitor
• can see post-tetanic facilitation (increase in TOF after tetanic stimulation)
• can be antagonized (reversed) by anticholinesterases
• do NOT see fasiculations (no depolarization)

Question 14

Succinylcholine

Answer 14

DOA: ultrashort

Onset: 0.5-1.5 min

Duration to 25% recovery: 6-8 min

ED95: 0.25 - 0.30

SE: histamine release, tachycardia (brady in peds), decresed BP

Question 15

Atracurium

Answer 15

DOA: Intermediate

Onset: 3-4 min

Duration to 25% recovery: 35-45 min

ED95: 0.15 - 0.25

SE: dose-dependent histamine release, small reflex tachycardia, minimal BP effect

Question 16

Cisatracurium

Answer 16

DOA: Intermediate

Onset: 5-7 min

Duration to 25% recovery: 35-45 min

ED95: 0.05

SE: no effect on HR, BP, no histamine release

Question 17

Vecuronium

Answer 17

DOA: Intermediate

Onset: 3-4 min

Duration to 25% recovery: 35-45 min

ED95: 0.05

SE: no histamine release, minimal BP and HR effect

Question 18

Rocuronium

Answer 18

DOA: Intermediate

Onset: 1-1.5 min

Duration to 25% recovery: 30-40 min

ED95: 0.30

SE: no histamine release, minimal tachy in kids, minimal BP effect

Question 19

Mivacurium

Answer 19

DOA: Short

Onset: 3-4 min

Duration to 25% recovery: 15-20 min

ED95: 0.08

SE: dose-dependent histamine releae, minimal HR and BP effect

Question 20

What is the purpose of giving muscle relaxants?

Answer 20

• to relax the skeletal muscles… more importantly to relax the VOCAL CORDS to pass the ETT through

Question 21

What are the benefits of muscle relaxation?

Answer 21

• improve surgical conditions (CV, neuro, transplant surgeries)
• facilitate endotracheal intubation

Question 22

What are the risks associated with muscle relaxation?

Answer 22

• no analgesia
• no anesthesia
• paralyzed but not anesthetized = bad!

Question 23

ED50 of muscle relaxant

Answer 23

dose at which a muscle relaxant produces a 50% depression of twitch tension in the nACHr

Question 24

A depolarizing NMB (sux) does 3 things:

Answer 24

1. desensitizes the nACHr
2. inactivates the VGaNa Channel and the NMJ
3. increases K+ permeability in the surrounding membrane
   * due to these effects, no AP can be generated and AChR blockade occurs!*

Question 25

Percentages of Twitch Response

Answer 25

- twitch response may not be reduced _until 70% of nAChR are blocked_ - twitch is completely elminated when _90%_ of receptors are blocked

Question 26

Peripheral Nerve Stimulation can answer 3 Questions:

Answer 26

- is NMB adequate? - is it inadequate? - can it be antagonized? * you must know how to use TOF IOT answer these questions!*

Question 27

Clinical tests to monitor cessation of NMB

Answer 27

- 5 second head lift - leg lift off OR table - strong handgrip from which you cannot remove 2 fingers - TV (only requires return of diaphragmatic tone) can pull 5mL/kg with 80% nAChR still occupied by NMDR

Question 28

Dibucaine Test

Answer 28

atypical BCE genetic variant, the dibucaine number communicates *how inhibited the action of BCE is by dibucaine.* - higher the number the more normal they are - low dibucaine number = longer DOA for sux ie: dibucaine number of 20-30 will prolong action of Sux up to 4-8 hours

Question 29

Treatment of Sux-induced Hyperkalemia

Answer 29

1. hyperventilation (make them alkalotic) 2. 1-2 mg Ca+ Chloride IV (helps w muscle contraction) 3. 50cc D50W + 10 U IV Insulin (adults) or 1 ml/kg D50W + 0.15 U/kg insulin (peds) 4. Na+ Bicarb 1 mEq/kg

Question 30

Dantrolene

Answer 30

Txs MH - initial dose 2 mg/kg - repeat 2 mg/kg up to 10 mg/kg if required - clinical response of decreased temp, decrease ETCO2 will indicate enough dantrolene has been given - redosing in PACU may be necessary

Question 31

MH may occur: (3 things)

Answer 31

1. after multiple unremarkable anesthetics (previous sux exposure) 2. during maintenace phase or post op from anesthesia 3. in pts w no prior fam hx of MH

Question 32

Phase II Block

Answer 32

- excessively large doses, repeat doses of Sux, or Sux infusions can result in a *phase II block*. This acts more like a non-depolarizing blockade of the NMJ. - if fade on TOF w a non-depolarizing block, the Sux has gone into a Ph II block. \>20 min reverse monitor/extubate at 0.9.

Question 33

Anticholinesterases

Answer 33

Neostigmine, pyridostigmine, etc. - given to reduce the activity of enzymes that break down ACh to IOT reverse the effects of non-depolarizing muscle relaxants - standard at end of anesthetic cases

Question 34

2 groups of non-depolarizing muscle relaxants:

Answer 34

benzylisoquinolinium and aminosteroid

Question 35

benzylisoquinolinium

Answer 35

d-tubocurarine (not in US) metocurine (60 min, not in US) atracurium (60 min) cis-atracurium (30-60 min) doxacurium (60+, not in US)

Question 36

aminosteroid compounds

Answer 36

pancuronium (60 min) vecuronium (20-50 min) rocuronium (most common, 20-50 min) pipercuronium (60+ min, rarely used)

Question 37

NDMRs are _____ \_\_\_\_\_\_ chemical compounds that are positively charged

Answer 37

NDMRs are **_quaternary ammonium_** chemical compounds that are positively charged