NMBD PHARM

Question 1

MOA succinylcholine

Answer 1

only depolarizing agent
Phase1:
-works by binding to the nicotinic receptor and causing it to remain open and thus depolarize the membrane–>transient fasciculations –> flaccid paralysis
Phase 2:
membrane repolarizes but the receptor is desensitized to ACh

Question 2

MOA of nondepolarizing neuromuscular blocking drugs

Answer 2

prevents the opening of the nicotinic receptor, they prevent depolarization of the muscle cell membrane and inhibit muscular contraction

Question 3

name the NMBD isoquinolone derivative

Answer 3

atracurium

Question 4

name the NMBD steroid derivatives

Answer 4

Pancuronium

Vecuronium

Question 5

describe how AChE inhibition is different for succinylcholine in phase I and phase II

Answer 5

AChE inhib auguments the clinical response in phase I, but it antagonizes the clinicl response in phase II

Question 6

the steroidal NMBD are highly ionized and are metabolized to what?

Answer 6

less potent 3-OH metabolite

Question 7

which nondepolarizing NMBD drug undergoes hepatic metabolism and hofmann elimination?

Answer 7

atracurium

Question 8

the metabolic product of atracurium is what?

Answer 8

laudanosine

Question 9

what does laudanosine cause?

Answer 9

seizures

Question 10

how is cisatracurium better than atracurium?

Answer 10

less dependence on hepatic inactivation, produces less laudanosine & releases less histamine
-all the advantages of atracurium w/ fewer side effects

Question 11

describe the duration of action of succinylcholine?

Answer 11

extremely short 5-10 mins

Question 12

how is succinylcholine rapidly metabolized?

Answer 12

mostly by pseudocholinesterase in the plasma

Question 13

how is the action of succinylcholine terminated in the NMJ?

Answer 13

diffusion from cleft

Question 14

what enzyme strongly influences the durability of succinylcholine?

Answer 14

plasma cholinesterase

Question 15

how could you have an increased risk for abnormally long duration of effect with succinylcholine?

Answer 15

if had a genetic defect with plasma cholinesterase

Question 16

how would you identify the genetic abnormality of plasma pseudocholinesterase w/ administration of succinylcholine?

Answer 16

do a dibucaine test

-colorimetric (inhibits the normal enzyme by 80% and abnormal enzyme by only 20%)

Question 17

what is the clinical application of succinylcholine?

Answer 17

used only in procedures where you only need a short effect

-e.g. rapid sequence intubation

Question 18

which steroidal NMBD has a moderate block on the cardiac M2 receptor?

Answer 18

pancuronium

Question 19

which depolarizing NMBD stimulates the cardiac M2 receptor?

Answer 19

succinylcholine (activating cardiac M2 receptor causes decreased CV capacity)

Question 20

which isoquinolone drug causes a slight histamine release that could result in increased vascular perm. and hypotension?

Answer 20

atracurium

Question 21

Name the 2 NMBD that cause slight histamine release?

Answer 21

atracurium

succinylcholine

Question 22

how can succinylcholine cause hyperkalemia?

Answer 22

in certain conditions (burns, trauma etc.) there is an upregulation of AChRs w/ 2 new isoforms–> K+ Efflux from muscle–>hyperkaemia

Question 23

name some of the adverse effects of succinylcholine

Answer 23

1. malignant hyperthermia
2. hyperkalemia in certain conditions (can be lethal)
3. hemodynamic changes
4. prolonged NM blockade
5. increased intraocular/intracranial pressure
6. Muscle pain (initial stim. of fibers)
7. myoglobinuria
8. Anaphylaxis

Question 24

how does malignant hyperthermia develop in pts taking succinylcholine?

Answer 24

they are genetically susceptible (aut. dominant)

-caused by an uncontrolled release of Ca2+ leading to rigor, heat, CO2, & lactate

Question 25

how would you treat malignant hyperthermia in pts taking succinylcholine?

Answer 25

dantrolene (blocks release of Ca2+ from SR) - remove trigger agent, hyperventilate w/ O2 - avoid CCB - corect hyperkalemia & acidosis, cool core temp.

Question 26

what are the important drug interactions with succinylcholine?

Answer 26

1. volatile anesthetics - isoflurane>sevoflurane, desflurane, halothane>N2O 2. antibiotics (aminoglycosides) - enhancement of blockade (pre-junctional P-type Ca2+ channels), depressed ACh release sim. to that caused by Mg2+ 3. local anesthetics - can depress via pre-junctional effect - block NM transmission in large doses 4. Other NM blocking drugs

Question 27

how can you over come the depolarizing effect of succinylcholine?

Answer 27

by administering a small dose of a non-depolarizing blocker

Question 28

Name the 3 AChE inhibitors

Answer 28

neostigimine edrophonium pyridostigimine

Question 29

which anticholinergic drugs would you use to overcome these AChE inhibitors: 1. neostigimine, 2. pyridostigimine

Answer 29

1. glycopyrrolate | 2. glycopyrolate

Question 30

what are some of the off target actions of the AChE inhibitors?

Answer 30

CV: decreased HR, dysrhythmias Pulm: bronchospasm, increased bronchial secretions cerebral: diffuse excitation GI: incr. peristalsis & glandular secretions GU: incr. bladder tone Opthalm: pupillary constriction

Question 31

so what drugs do you use if you want to terminate the NM blockade?

Answer 31

AChE inibitors

Question 32

what drugs do you use if you want to prevent the muscarinic effects caused by AChE inhibitors?

Answer 32

antimuscarinic agents like glycopyrrolate and atropine

Question 33

what are the therapeutic uses of NMBs?

Answer 33

1. Endotracheal intubation 2. adjuvant in surgical anesthesia - permits lower doses of anesthetics, fewer adverse events 3. short orthopedic procedures

Question 34

how are NMBs administered?

Answer 34

IV

Question 35

which NMBs would you use for a longer procedure?

Answer 35

steroidal or isoquinolone

Question 36

which NMB would you use for a shorter procedure?

Answer 36

succinylcholine

Question 37

which muscle is the last to be paralyzed and also the first to regain function when using NMBs?

Answer 37

the diaphragm

Question 38

do the NMBs cause any pain relief?

Answer 38

NO, only skeletal muscle paralysis

Question 39

what is the benefit of using peripheral nerve stimulation during NMBA administation?

Answer 39

results in using less meds, which allows for quick recovery of spontaneous ventilation & accelerated NM transmission when NMBA is discontinued

Question 40

what is the supramaximal stimulation?

Answer 40

the current that corresponds to 4 vigorous twitches when the train of four stimuli button is pushed. (after you go up 10mA to make sure there was no change)

Question 41

when 2 twitches are seen what percentage of the receptors are blocked?

Answer 41

80%

Question 42

when 1 twitch is seen what percentage of the receptors are blocked?

Answer 42

90%

Question 43

when no twitches are seen what percentage of the receptors are blocked?

Answer 43

100%