NMB agents 1/9

Question 1

order of muscles paralysis

Answer 1

rapid orbital muscles of eye>extremities>trunk>

intercostal>diaphragm

recovery occurs in reverse order

Question 2

depolarizing drug

(succinylcholine)

Answer 2

more stable agonist than ACh undergoing slow inactivation and also metabolized by cholinesterase

much more prolonged duration of action than ACh

Question 3

phase1 or depolarizing phase

Answer 3

fasciculations which can be prevented by pretreatment of small dose of non-depolarizing agent, but this will require adjustment of succs dose.

maintained depolarization will block action of ACh

Question 4

phase2 or desensitization block

Answer 4

succs will desensitize muscle nicotinic receptors resulting in repolarization of muscle,but endplate remains blocked.

this is most likely due to succs blocking ion channel of muscle nicotinic receptor

Question 5

picture of phase1 and 2 of succs

Answer 5

Question 6

adverse reactions to succs

Answer 6

apnea

hyperkalemia:massive muscle nerve damage,burn pts.this can lead to cardiac arrest.Also don’t use in children due to undiagnosed cardiomyopathy

increased intraocular pressure(eye injury)

increased gastric pressure(variable)

malignant hyperthermia:AD polymorphism,most often in ryanodine receptor

Question 7

hyperkalemia results from

Answer 7

release of K from the muscle via the nACHR where these receptors have been upregulated,following nerve injury or denervation

nerve activity regulates number of nACHR on muscle,normally keeping them at high density only at synapse

Question 8

genetic variability of plasma cholinesterase

Answer 8

ability to hydrolyze succs or mivacurium varies.

in some homozygous individuals for this variant,these blockers may have greatly prolonged actions

Question 9

other causes for lower plasma cholinesterase

Answer 9

pts with severe liver disease (plasma CHE comes from liver)

pts heterozygous for the genetic plasma CE variant

pts taking drugs with anti-plasma CE activity:pyridostigmine,esmolol,oral contraceptives

Question 10

non-depolarizing blocker

Answer 10

act simply as competitive inhibitors for ACh at muscle nictotinic receptors

Question 11

pharmacokinetics of NMB

Answer 11

poorly absorbed orally and must be given IV

some blockers eliminated or excreted by kidney–>longest 1/2 life and long duration of action.Even longer in kidney disease

some blocker are metabolized in liver–>shorter 1/2 life and shorter duration.longer in liver disease

some blockers hydrolyzed by plasma esterase and have shortest 1/2 lives and duration.plasma variants exist with poor hydrolysis activity prolonging 1/2 life of these blockers

Question 12

assessment of NMJ block

Answer 12

using peripheral nerve stimulation in order to adjust dose

train-of-four:brief sequence of 4 stimulation or tetany(burst of high frequency stimulation) will display what is known as fade when a non-depolarizing block is occuring

fade often involves a presynaptic action of non-depolarizing blocker at nerve ending itself,but main point is that it’s diagnostic of block.it goes away with recovery

Question 13

reversal of NMB

Answer 13

for all blockers except succs and mivacurium,use CE inhibitors (neostigmine)

increased ACh will compete away the blocker.to prevent excess ACh at muscarinic sites,use atropine or glycopyrrolate in order to prevent overshoot.

succs and mivacurium are used initially for rapid induction of paralysis and a long acting NMJ blocker is used to maintain paralysis.therefore succs is usually eliminated before reversal is initiated with neostigmine