Neuromuscular Blocking Agents Flashcards
Succ MOA
Mimics the action of Ach.
2 molecules of Ach linked by acetate methyl groups.
Partial agonist at nicotinic Ach receptors and attaches to one or both of the alpha subunits
depolarizing the ion channels at the post junctional membrane.
Sustained opening and depolarization prevents propagations of a new action potential.
Succ USE
Tracheal intubation
immobility during surgery
Succ Dose IV
1 mg/kg
range 0.3-1.1 mg/kg
Succ Dose IM
3-4 mg/kg
Succ Onset
30-60 seconds
Succ Duration
4-6 minutes
very short acting
Succ Peak
30-60 seconds
Succ Elimination
Excreted in the Urine
Succ metabolism
Hydolysis
Plasma Pseudocholinesterases
Succ Adverse reaction
Cardiac Hyperkalemia Myalgia Myoglobinuria IIOP IICP Salivation Histamine Release *rare
Succ Contraindications
Hypersensitivity/anaphylaxis *peds dt Duchennes Open globe MH Atypical plasma cholinesterase
succ classification
dicholine ester depolarizing neuromuscular blocker
Brand name of Succ
Anectine
How is Succ supplied?
20 mg/mL
10 mL vial
200 mg total
Brand name of Vecuronium
Norcuron
How is vec supplied?
1mg/mL
10 mg reconstitute to 1 mg/mL
Mechanism of Action of Vec
competitive antagonist with ACh at the nicotinic cholinergic receptor post synaptic membrane end plate bind to 1 alpha subunit --> NMB some presynaptic effect
what is Vec used for?
Tracheal intubation
Immobility during surgery
Facilitate mechanical
Ventilation
intubating dose of Vec
0.08-0.12 mg/kg
maintenance dose of Vec
0.01-0.015 mg/kg
dose for shivering with Vec
8-12 mg
onset of vec
2.5-3 minutes
DOA of vec
20-35 minutes
longer with elderly
45-65 minutes
peak of vec
3-5 minutes
half life of vec
65-75 minutes
elimination of vec
biliary: excretion/feces (40-75 %)
renal 25-35 %
redistribution and reversal in Cholinesterase I primary way to stop blockade
metabolism of vec
minimal hepatic
spontaneous deacetylation
active metabolite
Adv reactions with Vec
RARE- CV- bradycardia with opiods
cv collapse, edema, flushing, hypersensitivity reaction
contraindications with vec
Hypersensitivity/anaphylaxis reaction
BURN patients (>30% will be resistant for 5-7 days post insury)
Immobilization
Acute Quadriplegic Myopathy Syndrome in patients taking corticosteriods
brand name of Rocuronium
Zemuron
How is Rocuronium supplied?
10 mg/mL
classification of Rocuronium
intermediate acting
monoquaternary aminosteriod NDMB
derivative of vecuronium
it was designed to speed onset- less potent- more drug given able to occupy more receptors
MOA rocuronium
competitive antagonist with ACh at the nicotinic cholinergic receptor post synaptic membrane end plate bind to 1 alpha subunit --> NMB some presynaptic effect
use of roc
Tracheal intubation
Immobility during surgery
Facilitate mechanical
Ventilation
intubating dose of roc
- 45-9 mg/kg
0. 6 mg/kg
RSI dose for roc
0.6-1.2 mg/kg
1 mg/kg approaches the onset of such 30-60 sec
maintenance dose of rocc
0.1-0.2 mg/kg
10-20 minutes per dose of maintenance
defasciculation dose of roc
0.03-0.06 mg/kg
give 1.5-3 minutes before succ
onset of roc
1-2 minutes for intubating dose
peak of roc
4 minutes
half-life of roc
60-144 minutes
elimination of roc
feces 50%
urine 30%
reversal is primarily from redistribution
gradual metabolism
excrete gradually
Cholinesterase- Inhibitors inhibit acetylcholinesterase enzyme activity, stops Ach-esterase activity, increase Ach, stop block
metabolism of roc
Minimal hepatic
5-10% activity of the parents drug
Adverse reactions of Roc
Slight vagolytic tendencies- increase HR
HTN/HypoTN
Anaphylactoid rxn
RHF worsensed
Vessel irritant
Rare- ECG changes, anaphylactoid, anaphylaxis, arrhythmis, bronchospasm, edema at lite, hiccupts, pruritis, nausea, PVR increased, rash, rhonchi, shock, tackycardia, vomiting, wheezing
contraindications of roc
ypersensitivity
BURN patients
Immobilization- increased resistance
Acute Quadriplegic myopathy syndrome
In pt with corticosteroids
brand name of pancuronium
pavulon
classification of pancuronium
bisquaternary aminosteriod
non-depolarizing neuromuscular blocker
MOA of pancuronium
Long acting
Competitive antagonist with Ach at the nicotinic cholinergic receptors at the end plate of muscle. Binds to 1 alpha subunit of the post-synaptic receptor in a competitive fashioin.
use of pancuronium
Tracheal intubation
Immobility during surgery
Facilitate mechanical
Ventilation
intubating dose of pancuronium
- 1 mg/kg
0. 08-0.12 mg/kg
surgery dose of pancuronium
0.06-0.1 mg/kg
maintenance dose of pancuronium
0.01mg/kg (60-100 minutes after first dose and then 0.01 mg.kg every 25-60 m ins
continuous infusion dose of pancuronium
1-2 mcg/kg/min
how much to reduce the pancuronium dose with renal failure
50% reduction with renal impairment
onset of pancuronium
3-5 minutes
SLOW
duration of pancuronium
60-120 minutes
peak of pancuronium
3-5 minutes
half life on pancuronium
110 minutes
elimination of pancuronium
55-70% excreted in urine as unchanged drug
metabolism of pancuronium
Hepatic 30 %-45%
Deacetylation to active metabolite 1/3-1/2 activity of parent drug
adverse effects of pancuronium
CV: Vagolytic, increased HR, BP, CO
Derm: rash, itchy, erythema,burning in vein
GI- salivation
Neuro- muscle weakness
Resp- wheezing/bronchospasm
Hypersensitivity
contraindications of pancuronium
Hypersensitivity
BURN patients
Immobilization- increased resistance
Acute Quadriplegic myopathy syndrome
In pt with corticosteroids
brand name of mivacurium
mivacurium
how is mivacurium supplied?
50 mg/ 5mL or 100 mg/10mL
10mg/1mL
classification of mivacurium
bisquaternary benzylisoquinolinium
NDNMB
MOA of mivacurium
Competitive antagonist
main site of action on nicotinic cholinergic receipts
at the end plate of muscle
binding site of Ach
some presynaptic receptor effect (release of ACh)
80-90% of receptors must be blocked to see reduction in twitch height
use of mivacurium
tracheal intubation
immobility during surgery
facilitate mechanical ventilation
intubation dose of mivacurium
0.25 mg/kg
continuous infusion of mivacurium
3-15 mcg/kg/min
onset of mivacurium
2-3 minutes
peak of mivacurium
2-3 minutes
duration of mivacurium
12-20 minutes
half life of mivacurium
1-3 minutes
metabolism of mivacurium
Hydolyzed by plasma cholinesterases at 80% the rate of Succs metabolism
Hydrolysis is concentration dependent
More drug = faster hydrolysis
Adverse reactions with mivacurium
HISTAMINE → hypotension, tackycardia, bronchospasm
Caution in asthmatics
Hypotension more pronounced with hypertensive ptd
Pts with cholinesterase deficiency or reduced plasma cholinesterases
NO CV affect on cardiac muscarinic receptors (like pancuronium OR block ganglionic nicotinic receptors like d-tubocurine) so less hypotenion or tacky cardia but the histamine offsets these benefits
contraindications with mivacurium
Atypical plasma cholinesterase patients → prolonged blockade
asthmatics
what is a normal dibucane number?
80%
what is a dibucane number of someone who is homozygous for atypical variant form of atypical plasma cholineserases
20%
20% of plasma cholinesterase was inhibited by admin of dibucaine
3 hours of blockade
mivacurium and pancuronium
brand name of cisatracurium
nimbex
how is cisatracurium supplied
10 mg/5mL
20 mg/10 mL
2mg/1mL
classification of cisatracurium
intermediate acting
benzylisoquinolinium
NDNMB
how much more potent is cisatracurium than atrracurium?
4x
MOA of cisatracurium
Competitive antagonist
main site of action on nicotinic cholinergic receipts
at the end plate of muscle
binding site of Ach
some presynaptic receptor effect (release of ACh)
80-90% of receptors must be blocked to see reduction in twitch height
use of cisatracurium
tracheal intubation
immobility during surgery
facilitate mechanical ventilation
intubating dose of cisatracurium
0.15- 0.2 mg/kg
dose of cisatracurium after succs is used to intubate
0.1 mg/kg
maintenance dose of cisatracurium
0.03 mg/kg 40-60 minutes after initial dose
20 minute intervales
infusion dose of cisatracurium
3mcg/kg/min
1-2mcg/kg/min
consider reduction of infusion by 30-40 % with volitiles
onset of cisatracurium
2-3 min
peak of cisatracurium
3-5 minutes
duration of cisatracurium
20-35 minutes
half life of cisatracurium
22-29 minutes
metabolism of cisatracurium
NO ester hydrolysis
compared to atracurium
elimination of cisatracurium
77% hoffman elimination
non-enzymatic base catalyzed reaction to spontaneous degradation at normal body temp and pH
16 % renal
what accelerated hoffman elimination?
alkalosis
what slow hoffman elimination?
acidosis and hypothermia
how does the laundosine production compare between cisatracurium and atracurium?
cisatracurium is 5x less than atracuium
adverse reaction with cisatracurium
RARE/MILD
histamine- suggestive
bradycardia
contraindications with cisatracurium
Hypersensitivity
BURN patients
Immobilization- increased resistance
conditions that antagonize NMB
LESS BLOCK
alkalosis hypercalcemia demyelinating lesions peripheral neuropathies denervation infection muscle trauma DM acetylcholinesterase inhibitors burn injury 10 post injury peak 40 days decline 60 day
conditions that potentiate NMB
MORE BLOCK
electrolyte abnormalities severe hyponatremia severe hypocalcemia severe hypokalemia hypermagnesemia hypothemia neuromuscular disease acidosis acute intermittent porphyria eaton lambert syndrome myasthenia gravis calcium channel blockers aminoglycosides( Gent, tobra) inhalation anesthetics lithium magnesium salts procainamide quinidine loop diuretics
brand name of atracurium
atracurium
how is atracurium supplied
50 mg/5mL
100 mg/10mL
10mg/mL
classification of atracurium
intermediate acting
bisquaternary benzylisoquinolinium
NDNMB
10 sterioisomers
MOA of atracurium
Competitive antagonist
main site of action on nicotinic cholinergic receipts
at the end plate of muscle
binding site of Ach
some presynaptic receptor effect (release of ACh)
80-90% of receptors must be blocked to see reduction in twitch height
use of atracurium
tracheal intubation
immobility during surgery
facilitate mechanical ventilation
intubating dose of atracurium
0.4-0.5 mg/kg
Maintenance dose of atracurium
0.08-0.1 mg/kg every 20-45 minutes initially then 15-25 minutes
Initial dose after succ of atracurium
0.3-0.4 mg/kg
Infusion dose of atracurium
9-10 mcg/kg/min (maintained at 5-9 mcg/kg/min
ICU paralysis dose for atracurium
IV: bolus 0.4-0.5 mg/kg then 4-20 mcg/kg/min
onset of atracurium
2-2.5 minutes
duration of atracurium
20-35 min (95% recovery in 60-70 minutes)
peak of atracurium
3-5 minutes
half time of atracurium
2 minutes distribution to terminal 20 minues
elimination of atracurium
Hoffman Elimination 1/3 non-enzymatic base catalyzed reaction leading to spontaneous degradation at normal body temp and pH
LAUNDANOSINE- not active at NMJ causes CNS stimulation
70% laudanosine is excreted in bile- biliary obstruction can lead to accumulation of the metabolite
what does laundanosine cause as a metabolite of atracurium
Increased volatile requirement
Vasodilation
metabolism of atracurium
Hydrolysis by non-specific plasma esterases 2/3
Laundosin is the metabolite for both ester hydrolysis and Hoffman
Non-renal/hepatic
adverse reactions of atracurium
Mild/RARE
Flushing
Increase HR decrease MAP 5 min recovery
Facial and truncal flushing
Bradycardia
0.5 mg/kg
contraindications with atracurium
AVOID WITH ASTHMATICS
Burns
Immobilization
Hypersensitivity/ anaphylactic
typical dose with atracurium
50 mg for intubation may need more if big male need to re-dose after 30 minutes usually about 10-20 mg lasts 30 minutes takes 2 minutes to get on board
