Nondepolarizing NMB

Question 1

what are the chemical characteristics of nondepolarizing NMB drugs?

Answer 1

• structured similar to ACh
• have one or two quaternary nitrogens making them highly ionized and polar
• lipid insoluble, can not cross the BBB, placental membrane, or GI epithelium (poorly absorbed orally)
• quaternary ammonium found in makeup so women are typically already exposed to allowing antibodies to form. allergic reactions most commonly seen in women with SCh and Rocuronium

Question 2

what are the two classes of nondepolarizing NMB

Answer 2

• benzylisoquinoline class
• end in -curium
• steroidal class
• end in -curonium

Question 3

what drugs are in the benzylisoquinoline class?

Answer 3

d-Tubocurarine (Curare)
Atracurium (Tracrium)
Cisatracurium (Nimbex)
Doxacurium (Nuromax)
Mivacurium (Mivacron)

Question 4

what drugs make up the steroidal class?

Answer 4

pancuronium (Pavulon)
vecuronium (Norcuron)
pipecuronium (Arduan)
rocuronium (Zemuron)
rapacuronium (Raplon)

Question 5

what is the mechanism of action for nondepolarizing agents?

Answer 5

compete with ACh to bind with the alpha subunits on the postjunctional ACh receptors and, thus, prevent the ion channel from opening, preventing depolarization of the muscle cell membrane

Question 6

what are some characteristics of nondepolarizing NMB?

Answer 6

• decreased twitch response to a single stimulus
• fade with tetanus and TOF
• posttetanic potentiation
• enhanced by other nondepolarizing NMB
• antagonized by anticholinesterase drugs

Question 7

how does onset of the NMB compare to the ED95?

Answer 7

the less potent the drug (higher the ED95), the quicker the onset
*this is because if more molecules must be given per dose, resulting in more molecules reaching the NMJ to cause a more rapid creation of blockade

Question 8

what is the priming principle?

Answer 8

• to facilitate rapid intubating conditions with nondepolarizing agents
• a small dose is given prior to induction to allow some receptors to be occupied and minimize time required for the remaining receptors to be blocked by remainder of intubating dose
• either 1/10 of intubating dose or 1/3 of ED95
• not helpful with short acting rocuronium

Question 9

other than priming, how can you speed onset?

Answer 9

simply increase the dose of the NMB

*disadvantage is this also increases side effects and prolongs duration

Question 10

which drugs are short acting nondepolarizers?

Answer 10

mivacurium

*on “backorder”

Question 11

which drugs are intermediate acting nondepolarizers?

Answer 11

atracurium
cisatracurium
vecuronium
rocuronium

Question 12

which drugs are long acting nondepolarizers?

Answer 12

pancuronium
doxacurium
pipecuronium
d-tubocurarine

Question 13

what are the two parts of duration?

Answer 13

• distribution which occurs rapidly

- clearance which occurs slower

Question 14

if a drug is excreted by the kidneys how does that affect the duration?

Answer 14

longer half lives and longer duration (>60 min)

Question 15

metabolism and clearance through the liver affects duration how?

Answer 15

shorter half lives and duration

*steroid family (-curonium)

Question 16

describe d-Tubocurarine (Curare)

Answer 16

-naturally occurring benzylisoquinoline obtained from
the Chondodendrum tomentosum plant found in the
Amazon
-long acting; eliminated by renal and hepatic
*histamine release
*precurarization”: defasciculation dose of 3 mg

Question 17

describe pancuronium (Pavulon).

Answer 17

• most commonly seen long acting NMB
• aminosteroid
• metabolized mostly (80% unchanged) renal
• 10-40% metabolized in the liver
• avoid in renal failure patients. slows clearance 2-3x

Question 18

what are the ED95 and intubating dose of pancuronium?

Answer 18

ED95: 0.07 mg/kg

intubating dose: 0.1 mg/kg

Question 19

what are the onset and duration for pancuronium?

Answer 19

onset 3-5 minutes

duration 60-90 minutes

Question 20

what cardiac effects does pancuronium have?

Answer 20

-vagolytic effects due to 1) vagal blockade at muscarinic receptors and 2) stimulation of the sympathetic nervous system (cause release of ne and prevent its reuptake)
*10-15% increase in HR, MAP, and CO
*great drug with babies since their CO depends on HR
*used commonly in cardiac cases with heavy opioid use
to reverse the resulting bradycardia
*do not use with CAD patients if heavy opioid use is not
involved or it will increase the cardiac O2 demand and
decrease coronary muscular supply since there is less
time in diastole with tachycardia
*increase in HR inversely related to baseline HR, not dose or rate of administration
-lower baseline HR, greater increase in HR
-esp. if AV conduction is altered like in a-fib

Question 21

describe doxacurium (Nuromax).

Answer 21

• long acting benzylisoquinolone
• elimination mostly unchanged by the kidneys and some unchanged by the liver
• originally made for longer neuro cases, not commonly used
• no cardiac effects

Question 22

what are the ED95 and intubation doses for doxacurium?

Answer 22

ED95: 0.03 mg/kg

intubating dose: 0.05-0.08 mg/kg

Question 23

what are the onset and duration for doxacurium?

Answer 23

onset: 4-5 minutes
duration: 60-90 minutes

Question 24

describe pipecuronium (Arduan)

Answer 24

• long acting, steroid family
• elimination unchanged in the urine (no metabolism so no prolonged effect with liver disease)
• no cardiac effects or histamine release

Question 25

what are the ED95 and intubating doses for pipecuronium?

Answer 25

ED95: 0.05 mg/kg | intubation dose: 0.085 mg/kg

Question 26

what are the onset and duration for pipecuronium?

Answer 26

onset: 3-5 minutes duration: 60-90 minutes

Question 27

describe vecuronium (Norcuron).

Answer 27

- intermediate monoquaternary analog of steroid class pancuronium * elimination hepatic metabolism and 40% excreted unchanged in the bile; 30% unchanged in urine * more lipid soluble than pancuronium, allowing greater passage into hepatocytes for clearance causing a shorter duration * prolonged action with renal failure and if large dose, liver dysfunction * no cardiac effect * no histamine release

Question 28

why is duration of vecuronium prolonged in infants less than 1 yr.

Answer 28

- possibly due to immature hepatic enzymatic systems - increased volume of distribution - decreased biliary clearance

Question 29

what effect does vecuronium have on histamine?

Answer 29

can inhibit the catabolism of histamine by inhibiting histamine-N-methyl-transferase *be careful if given with other histamine releasing drugs like antibiotics

Question 30

what are the ED95 and intubating doses of vecuronium?maintenance dose? infusion rate?

Answer 30

ED95: 0.05 mg/kg intubating dose: 0.1 mg/kg maintenance dose: 0.015 mg/kg infusion: 1mcg/kg/min

Question 31

what are the onset and duration of vecuronium?

Answer 31

onset: 2-3 minutes duration: 45-60 minutes

Question 32

describe rocuronium.

Answer 32

- intermediate acting, derivative of steroidal vecuronium * elimination: 50% unchanged in bile; > 30% in urine * prolonged in renal failure (elderly) and liver disease (especially if an infusion or repeated doses with) * anaphylactoid reactions (not Ige mediated but same reaction as anaphylaxis) * significant increase in duration with increased dose * greater concentration of inhalation agents prolongs duration * slight vagolytic effect (inconsistent) * priming does not effect onset, an increased dose will increase onset

Question 33

what are the indications for rocuronium?

Answer 33

rapid sequence only related to aspiration *do not use in difficult airway cases b/c duration is longer than SCh and pt will become hypoxic if unable to secure airway

Question 34

what are the ED95 and intubating doses of rocuronium? maintenance dose? infusion?

Answer 34

ED95: 0.3 mg/kg Intubating dose: 0.6 mg/kg maintenance: 0.1 mg/kg infusion: 10-12 mcg/kg/min

Question 35

what are the onset and duration of rocuronium?

Answer 35

onset: 1-2 min duration: 20-35 minutes

Question 36

describe atracurium (Tracrium).

Answer 36

-intermediate acting benzylisoquinolone diester -elimination: Hofmann elimination (spontaneous breakdown) at normal temperature and pH; metabolism by plasma esterases *organ independent *Laudanosine- metabolite of both routes is a CNS stimulant (cause seizures and cerebral excitation in animals) -clinically increased levels not reached in humans -prolonged elimination in renal failure patients since metabolized in the liver *histamine release: increased HR, decreased MAP, decreased SVR, flushing (3x ED95) -not good in asthma, COPD, irritable airway -avoid in CAD and pts. who tachycardia effects -will see (esp in children) turn red/flushed and see whelps at site and up arm

Question 37

how can you avoid histamine effects of histamine release with atracurium?

Answer 37

- slow administration, 30-75 seconds | - pretreatment with H1 blockers (Benadryl) and H2 blocker (Pepcid)

Question 38

what are the ED95 and intubating doses for atracurium? maintenance dose? infusion rate?

Answer 38

ED95: 0.2 mg/kg intubating dose: 0.5 mg/kg maintenance dose: 0.07 mg/kg infusion rate: 6-8 mcg/kg/min

Question 39

what are the onset and duration of atracurium?

Answer 39

onset: 2-3 minutes duration: 20-35 minutes

Question 40

describe cisatracurium (Nimbex).

Answer 40

- intermediate acting isomer of atracurium * elimination: solely Hofmann elimination * organ independent elimination * no cumulative effects- good for infusions * production of laudanosine less (1/5) due to only one pathway * no histamine, minimal CV effects

Question 41

what are some indications for cisatracurium use?

Answer 41

- organ failure - intermediate length case - need to avoid histamine effects (CV or pulmonary) - infusion

Question 42

what are the ED95 and intubating dose of cisatracurium? maintenance dose? infusion rate?

Answer 42

ED95: 0.05 mg/kg intubating dose: 0.1-0.2 mg/kg maintenance dose: 0.03 mg/kg infusion: 1-2 mcg/kg/min

Question 43

what are the onset and duration of cisatracurium?

Answer 43

onset: 2-3 minutes duration: 20-35 minutes

Question 44

describe mivacurium (Mivacron).

Answer 44

- short acting benzylisoquinoline * not indicated for rapid sequence since onset 1.5-3 min * elimination: plasma cholinesterase at 70-80% (like SCh) * three stereoisomers: cis-trans, trans-trans (1/2 lives of 2 min), cis-cis (1/2 life of 53 min) * histamine release with more than 2x ED95 (avoid by giving divided doses) * CV effects with 3x ED95, decreased MAP

Question 45

what can effect duration of mivacurium?

Answer 45

-neostigmine can slow recovery (20-60 min) inhibits activity of plasma cholinesterase establish that recovery is already occurring prior to giving anticholinesterase (use edrophonium) -causes a prolonged block in patients with atypical plasma cholinesterase -patients with renal or hepatic failure may have prolonged duration if plasma cholinesterase activity decreased

Question 46

what are the ED95 and intubating doses for mivacurium? maintenance dose? infusion rate?

Answer 46

``` ED95: 0.08 mg/kg intubation dose: 0.15-0.2 mg/kg maintenance dose: 0.1 mg/kg infusion rate: initial 9-10 mcg/kg/min; then 6-7 mcg/kg/min ```

Question 47

what are the onset and duration of mivacurium?

Answer 47

onset: 1.5-3 minutes duration: 12-20 minutes

Question 48

cardiovascular effects of nondepolarizing agents

Answer 48

-pancuronium: vagolytic, tachycardia, HTN, dysrhythmias, enhanced AV conduction -atracurium and mivacurium: histamine release from mast cells causes hypotension and tachycardia (dec SVR) *no CAD pts. *the bigger the dose and more rapid the administration allows greater concentration around the mast cell *prophylaxis: low doses, slow administration, pretreat with H1 and H2 blockers -vecuronium: interferes with the catabolism of it causing more to remain active *think is no CV effect ok or will it offset the effect of opioids?