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Flashcards in Nondepolarizing NMB Deck (48)

what are the chemical characteristics of nondepolarizing NMB drugs?

-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


what are the two classes of nondepolarizing NMB

-benzylisoquinoline class
* end in -curium

-steroidal class
*end in -curonium


what drugs are in the benzylisoquinoline class?

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


what drugs make up the steroidal class?

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


what is the mechanism of action for nondepolarizing agents?

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


what are some characteristics of nondepolarizing NMB?

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


how does onset of the NMB compare to the ED95?

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


what is the priming principle?

-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


other than priming, how can you speed onset?

simply increase the dose of the NMB
*disadvantage is this also increases side effects and prolongs duration


which drugs are short acting nondepolarizers?

*on "backorder"


which drugs are intermediate acting nondepolarizers?



which drugs are long acting nondepolarizers?



what are the two parts of duration?

-distribution which occurs rapidly
-clearance which occurs slower


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

longer half lives and longer duration (>60 min)


metabolism and clearance through the liver affects duration how?

shorter half lives and duration
*steroid family (-curonium)


describe d-Tubocurarine (Curare)

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


describe pancuronium (Pavulon).

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


what are the ED95 and intubating dose of pancuronium?

ED95: 0.07 mg/kg
intubating dose: 0.1 mg/kg


what are the onset and duration for pancuronium?

onset 3-5 minutes
duration 60-90 minutes


what cardiac effects does pancuronium have?

-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


describe doxacurium (Nuromax).

-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


what are the ED95 and intubation doses for doxacurium?

ED95: 0.03 mg/kg
intubating dose: 0.05-0.08 mg/kg


what are the onset and duration for doxacurium?

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


describe pipecuronium (Arduan)

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


what are the ED95 and intubating doses for pipecuronium?

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


what are the onset and duration for pipecuronium?

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


describe vecuronium (Norcuron).

-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


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

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


what effect does vecuronium have on histamine?

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


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

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


what are the onset and duration of vecuronium?

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


describe rocuronium.

-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


what are the indications for rocuronium?

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


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

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


what are the onset and duration of rocuronium?

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


describe atracurium (Tracrium).

-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


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

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


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

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


what are the onset and duration of atracurium?

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


describe cisatracurium (Nimbex).

-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


what are some indications for cisatracurium use?

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


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

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


what are the onset and duration of cisatracurium?

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


describe mivacurium (Mivacron).

-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


what can effect duration of mivacurium?

-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


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

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


what are the onset and duration of mivacurium?

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


cardiovascular effects of nondepolarizing agents

-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?