Muscle Relaxants, NMBA (L&J Chp 14) Flashcards

Question

Pancuronium

Answer 1

- Non-depol (competitive) NMBA - Steroid molecule-based structure - Dose-dependent onset ~5' - Repeated doses = cumulative effect --> infusion not common - Duration of action 40-60' - Mostly renal excretion with some hepatic metabolism --> prolonged duration of action in patients with renal insufficiency

Answer 2

- Blocks cardiac muscarinic R, increasing HR - Effect varies among species - usually not a clinical concern - Muscarinic blocking effect, associated tachycardia appear to be due to second positive charge on steroid ring

Answer 3

Pancuronium - single methyl group (and thus positive charge) = vecuronium --> no CV effects

Answer 4

- Short-acting, non-depolarizing (competitive) NBMA - Benzolisoquinoline structure similar to that of d-tubocurarine - Dose-dependent onset approx 5' - Dose-dependent duration in dogs approx 30' - Repeated doses do not tend to be cumulative so longer term maintenance of NMB via infusion is viable

Answer 5

- Almost half of drug degraded by Hoffmann elimination, nonspecific ester hydrolysis - Remaining fraction of the drug degraded by undefined routes --> no evidence of prolonged action in humans with renal or hepatic insufficiency - Can be safely given to patients with hepatic or renal insufficiency without an increase in duration of action

Answer 6

Does not require enzymatic activity | Is not a biologic proces

Answer 7

Drug should be refrigerated | Supplied at pH 3.25-3.65 to slow degradation

Answer 8

- When injected at physiologic pH/temperature, spontaneously decomposes into laudanosine and quaternary monoacrylate

Answer 9

- Byproduct of atracurium, cis-atracurium metabolism - has potential to induce seizures - Dependent on hepatic clearance --> plasma concentrations may be elevated in patients with hepatic insufficiency

Answer 10

-Laudanosine-induced CNS stimulation/resultant seizures unlikely in clinical patients unless drug used for prolonged periods of time as might occur in intensive care settings

Answer 11

- Hypothermia - Hofmann elimination is pH/temperature dependent so hypothermia will increase duration of NMB and decrease infusion rate necessary to maintain NMB

Answer 12

- Accomplished by several plasma esterases not related to plasma cholinesterase - Duration of action not prolonged in the presence of cholinesterase inhibitors (in contrast to depolarizing NMBA succinylcholine)

Answer 13

-Associated with histamine release --> varying degree of resultant hypotension

Answer 14

- Prototypical benzylisoquinolone NMBA | - Most potent histamine-releasing NMBA

Answer 15

- Require several times the ED95 dose required for NMB before appreciable amounts of histamine are released - Hypotension, tachycardia not usually observed in clinical cases

Answer 16

-racemic mixture of ten optical isomers

Answer 17

- 1R-cis, 1R'-cis isomer | - Comprises approximately 15% of racemic atracurium --> approx 4x potency, reduced potential for histamine release

Answer 18

-Similar to atracurium

Answer 19

- Hofmann elimination responsible for greater than half administered dose of cisatracurium - No ester hydrolysis

Answer 20

- Hofmann elimination --> laudanosine production | - Since 4x as potent as atracurium, can give lower dose so have less laudanosine production

Answer 21

- NMJ | - Motor end plate

Answer 22

-Forms interface btw large myelinated motor nerve and muscle supplied by the nerve

Answer 23

- Prejunctional motor nerve ending - Synaptic cleft - Postjunctional membrane of the skeletal muscle fiber

Answer 24

Nicotinic R

Answer 25

Nicotinic R

Answer 26

- Receptor type on the pre/post junctional area of the NMJ | - Bind/respond to ACh or another suitable ligand

Answer 27

Thought to be important in the synthesis and mobilization of ACh stores but not in its release

Answer 28

- Junctional | - Extrajunctional

Answer 29

- Found on the motor endplates of normal adult animals - Responsible for binding with released ACh --> effecting muscle ctx --> therefore responsible for relaxant effect when NMBA administered

Answer 30

- Not normally present in muscles of typical adults | - Present in neonates

Answer 31

- Synthesized by muscles receiving less than normal degree of motor nerve stimulation - Produced by muscles following spinal cord or peripheral nerve injury or after period of disuse as when limb is casted

Answer 32

Not restricted to the motor endplate | May be located over the entire muscle surface

Answer 33

- Appear to be more sensitive to depolarizing NMBA, less sensitive to non depolarizing NMBA - If the degree of neural deficit is severe, extrajunctional receptors may be numerous and widely distributed over the muscle membrane - Such patients may very different responses to actions of depolarizing NMBA and thus profound release of intracellular K+ with concomitant adverse cardiac effects may result if succinylcholine is administered to these patients

Answer 34

Competitive Whichever suitable ligand is present in highest concentrations in the vicinity of the receptor will win the competition and affect the outcome

Answer 35

- Two molecules of ACh required to bind to each of the alpha subunits on the R - Antagonists: need only to bind to one of the subunits to present normal NM transmission - Ctx of the muscle does not occur in response to motor nerve depolarization and paralysis results

Answer 36

Dynamic process of binding and release Depends on the sheer number of receptors present (10-20,000/micrometer^2) So: success or failure of NM transmission in the presence of NMBA is determined by the concentration of NMBA vs concentration of ACh

Answer 37

success or failure of NM transmission in the presence of NMBA is determined by the concentration of NMBA vs concentration of ACh

Answer 38

Favoring of muscle contraction

Answer 39

Favoring paralysis

Answer 40

- Increasing concentration of ACh compared with concentration of NMBA will increase probability that ACh will win competition for R and restore normal NM transmission - Clinically: accomplished by administration of AChE inhibitors

Answer 41

- eg neostigmine - Available ACh not degraded immediately but persists within the synapse - Able to repeatedly interact with receptors --> tips competitive balance in favor of ACh --> more R participate in current flow, global muscle strength increases - Interaction also seen as the activity of a NMBA wanes due to drug elimination

Answer 42

- Derivative of vecuronium | - Approximately 1/8th potency

Answer 43

-Similar molecular weights but rocuronium has a lower potency so larger injected dose of rocuronium places greater number of molecules near NMJ --> more rapid onset of blockade

Answer 44

- Similar duration of atracurium, vecuronium - More rapid onset but cannot provide optimal conditions for human intubation as quickly as succinylcholine - Virtually no CV effects - No histamine release

Answer 45

Primary route - hepatic clearance | Small fraction eliminated by the kidney

Answer 46

Administration of suggammadex

Answer 47

Used for reversal of rocuronium, vecuronium | Chelating agent that preferentially binds to, physically removes the NMBA from the motor end plate

Answer 48

Steroid relaxant derived from pancuronium

Answer 49

- Manipulation of the steroid structure --> greatly reduced antimuscarinic effects - Piper = free of tachycardic effects while retaining long duration of action - Can cause hypotension in dogs

Answer 50

-Eliminated primarily by renal route with smaller fraction undergoing biliary excretion

Answer 51

-First NMBA devoid of CV effects

Muscle Relaxants, NMBA (L&J Chp 14) Flashcards

(75 cards)