Muscle Relaxants Flashcards
Acetylcholine
Neurotransmitter at NMJ
Formation
________ + ________ ( enyzme
_________________ ) → Ach
Destruction
Action of ________ present in ________
Choline + acetyl co A
choline acetyl transferase
acetyl cholinesterase
synaptic cleft
Neuromuscular Transmission :
Depolarisation of motor nerve→ ____ propagated to _______→↑permeability to ________ & ________ of vesicles→Ach release
Ach cross synaptic cleft & bind to receptors →Dep. of _________________ & generation of AP →_____ channels open→_____ release→ _______ + _________ coupling → CONTRACTION
AP; NMJ; calcium; exocytosis
muscle end plate; Na; Ca
actin + myosin
Factors which influence NMT
Prevent Ach SYNTHESIS
_______________
Prevent Ach RELEASE
_______________, _______________, ____________, _______________
Deplete Ach STORES
______________
Hemicholinium
↓calcium, ↑magnesium Botulism Aminoglycosides
Tetanus
Factors which influence NMT
Block Ach RECEPTORS
_______,________________
Block action of acetyl- cholinesterase
_______________,______________
Muscle relaxants Myasthenia gravis
Anticholinesterases
Organophosphorus
What are Muscle Relaxants?
Drugs used to impair _______________ and used to provide skeletal muscle _________ during anaesthesia or critical care.
neuromuscular transmission
relaxation
Indications for Muscle Relaxants :
To Facilitate :
_________
__________
____________
Tracheal intubation
Ventilation
Surgical access
Classification
DEPOLARISING MR ( Competitive or Non-Competitive?))
Resemble Ach →bind to receptors → _____________ (_____________)
Not metabolised by _____________.
Concentration in synaptic cleft remains high.
Reversal by _____________ from ________ & ___________ by _____________ Phase ___ block
No ___________
No _____________
Non-Competitive
initial depolarisation ; fasiculations
acetylcholinesterase ; diffusion ; NMJ
Hydrolysis ; pseudocholinesterase Phase I
fade; post tetanic potentiation
Depolarizing Block
Because _______ resembles Ach it stimulates the receptors first causing _________
•It then stays fixed on receptors as it is not metabolised by ____________.
•It therefore prevents Ach from reacting with the receptors and allowing NMT.
suxamethonium; fasiculations
acetylcholinesterase
NON DEPOLARISING MR(Competitive or Non-Competitive?)
Bind to Ach receptors (with or without?) initial depolarisation; (fasciculation or no fasiculations?) .
Phase ___ block
Exhibit ______
Exhibit _______________
Competitive ; without
II; fade; post tetanic potentiation
Non-Depolarising MR
Reversal- redistribution, metabolism, excretion.
_______________ - inhibits ______________→ ↑ Ach.
Potentiated by __________,__________ agents, (alkalosis or acidosis?) , ↓ K, ↑ Mg, ↓ Ca.
Anti cholinesterase; acetyl cholisterase
aminoglycosides ; volatile
Acidosis
Monitoring the NMJ Peripheral nerve stimulator
Assess _______ , _______, _______ or _______ response to electrical stimulus.
Use _______, _______ or _______ nerve
visual, tactile, mechanical or EMG
ulnar, facial or tibial nerve
Monitoring the
Patterns of stimulation.
Single twitch (_____ – ______ Hz).
Tetanic stimulation (____ - ____ Hz. x ______ s)
Post tetanic stimulation using single twitches
Train of four —____ twitches at ____ hz.
0.1 – 1.0 Hz
50 - 100 Hz. x 3- 5s
4 twitches at 2 hz.
Train of Four (TOF) twitches:
Only 3 twitches → ____% block
Only 2 twitches → ____%
Only 1 twitch → ____%
No twitch →____%
75% ; 80% ; 90% ; 100%
Train of Four (TOF) twitches:
____ % reqd for intubation
____ –____% for maintenance
___ –____% before attempting reversal
100
90-100
75-80
Train of Four (TOF) twitches:
100 % reqd for __________
90 –100% for __________
75 –80% before __________
intubation
for maintenance
before attempting reversal
BefORE MR(NO BLOCK)
No MR given, Ach crosses NMJ and stimulates the receptors causing NMT •Nerve stimulator produces ______ twitches
•Also applicable to ________ of ________
full
reversal of NDMR
After MR (Complete block)
•NDMR blocks the Ach receptors and prevents further NMT
•Nerve stimulator produces ______ twitches on stimulation
•__________ can be carried out.
no; Intubation
Partial Block
•NDMR gets ______________ and few Ach molecules can now stimulate the receptors •Nerve stimulator produces __________ amplitude.
metabolised
reduced twitch
FADE
With a partial block- _____ MR show a _________↓ amplitude – No fade
•With a partial block- ________ MR show a __________ ↓ in amplitude from the 1st to the 4th twitch in a TOF - Fade
Dep; uniform
non-dep; gradual
Post-Tetanic Facilitation
With a partial _______ block, tetanic stimulation recruits Ach molecules to
the synaptic cleft
•Subsequent twitches have __________ – Post tetanic facilitation/stimulation
non-dep; ↑amplitude
Suxamethonium
Clinical Practice in 1951
____ Ach molecules
Dose
_______ mg/kg ____
____ mg/kg ___/____
Onset: __________
Indicated in (slow or rapid?) sequence induction
Duration ________________
2
1–2; I.v
2; I.m/s.c
30-45 secs; rapid
2 –5 mins
Suxamethonium
Best for anticipated ________________
difficult intubation
Suxamethonium
CVS - _____cardia
More frequent in (children or adults?)and with a ______ dose given within ________.
MSS - ________ → Postoperative __________
↑ ————-,______,__________ pressures
Hyperkalaemia-↑K by 0.5meq/L x3–5 mins
↑with _________ injuries , ______
Brady; children; 2nd ; 5 mins
Fasiculations; myalgia
Intragastric, intraoccular, intracranial
Denervation; burns
Suxamethonium
Can cause ________________, a
Premonitory sign of ________________
Myoclonus
Adverse drug reaction
Malignant hyperthermia
masseter spasm
Suxamethonium is metabolised by ______________ which has a reduced Conc in : ?????(list 4)
pseudo- cholinesterase
Pregnancy
- Liver disease,
- Malnutrition,
- ↓ protein states
Pseudocholinesterase
Inhibitors
- ___________
- ___________
- ___________
Results in ____________
- Ecothiopate
- Phenelzine
- Trimetaphan
prolonged apnoea
Dibucaine Number
Normal DN ____-____%
Heterozygous DN ______% -apnoea x _________ min
Homozygous DN _________% - apnoea x _________
75–85
40-60; 10 – 20
15-25; 6-8 hours
Non-depolarising MR
CLASSIFICATION
________________
_____________________
Benzylisoquinolines
Aminosteroids -Vagolytic
Non-depolarising MR
CLASSIFICATION
Benzylisoquinolines -Release __________
Examples : __________ , __________, __________ __________
Histamine
Atracurium ,Cis-atracurium, Mivacurium Doxacurium
Non-depolarizing MR
Aminosteroids -Vagolytic
_____________ , _____________, _____________,
_____________
Pancuronium, Vecuronium Pipecuronium,
Rocuronium
Non-depolarizing MR
There’s a
_________ dose for intubation , and ____________ dose (which is ________ of _________ dose)
Loading; intubation
Maintenance; 1⁄3 -1⁄4
loading
Atracurium :
1980
Solution stored at _______oC
Dose
Loading dose -____mg/kg
Maintenance- _____-______
Infusion ___-____ mcg/kg/min
Onset ____-_____ mins
Duration ________ mins
2 – 8
0.5 ; 1/3 – 1⁄4
5-10
1.5 – 2
20 - 30
Atracurium
Effects
_____________
_______________
CV stability
Bronchospasm
Atracurium
Metabolism
•____________ degradation 50-60% (____________ dependent, ____________ but ________ and _________ dependent)
• _________________
Hoffman’s degradation ; Non organ dependent
Non enzymatic ; pH and temp dependent
Ester hydrolysis
Laudanosine - Product of ____________, can cause _______________ & _________ especially in ________ failure.
Hoffman metab.
CNS excitability ; Seizures; liver
Cis-Atracurium
___________ of atracurium
DOSE - ____-_____mg/kg
ONSET - _____-______
DURATION – _____-______
Isomer
0.1 – 0.2
1.5 –2 mins
30 – 40 mins
Cis-Atracurium
EFFECTS
____________ release
____________
METAB -70 – 80 % __________
(More or Less?) ____________ produced as less total dose used.
No histamine; CV stability
Hoffmans; less
laudanosine
Mivacurium
1993
Mivacurium
DOSE - _____ – _____ mg/kg
ONSET –_____ –_____ mins
DURATION –_____ – _____ mins
DOSE - 0.15 – 0.2 mg/kg
ONSET –1.5 –2 mins
DURATION –10 – 20 mins
Mivacurium
EFFECTS
_____________
(Small or Large?) dose given rapidly → ________ release.
METAB - _______________________.
CV stability
Large
histamine
Plasma cholinesterase
Alternative to suxamethonium especially in paeds is ???
Mivacurium
Doxacurium :
1991
DOSE - _______ mg/kg
ONSET – ______ mins.
DURATION - _____________.
1991
DOSE - 0.05 mg/kg
ONSET – 4- 5 mins.
DURATION - 1-3 hours.
Doxacurium :
EFFECTS
____________ release.
_____________
METAB
(Slow or Fast?) hydrolysis by _____________.
Excreted (changed or unchanged?) by liver and kidneys.
USES - ____________ surgery-neuro, cardio.
No histamine; CV stability
Slow ; plasma cholinesterase
Unchanged; Prolonged
Pancuronium :
1967
________________ compound.
DOSE – _____ – _____ mgkg
ONSET – _____ –_____ mins.
DURATION – _____ – _____ mins.
Bisquartenary amino- steroid
DOSE – 0.08 – 0.1mgkg
ONSET – 2 – 3 mins.
DURATION – 40 – 60 mins.
Pancuronium
EFFECTS
___________ / ___________
↑ ____, _____, _____.
Useful in _______
Caution in ___________ or ___________ dx
Vagolytic / Sympathomimetic
↑ HR, BP, CO.
shock
hypertension ; Ishaemic Heart dx
Pancuronium
METAB
By the ______ with _______ excretion
Presence of __________________, so caution in ________________
Liver; renal
Active metabolites
renal dysfxn.
Vecuronium
1983
Comes as _________
DOSE -____ – ____mg/kg
ONSET - _____ mins.
DURATION -_________ mins
EFFECTS - ________________
METAB – 75% _______. 25% _______ . ______ admin.
powder
0.08; 0.12 ; 1.5; 20 – 30
CV stability; biliary; renal
ICU
Pipecuronium :
1990
DOSE – ______ – ______ mg/kg
ONSET – ______ – ______ mins.
DURATION - ______ – ______ mins.
0.06 – 0.1mg/kg
2.5 – 3 mins.
90 – 120 mins.
Pipecuronium
EFFECTS - ___________
METAB - 70% _______ . 30% _______.
CV stability
Renal
Biliary
Rocuronium :
1994
DOSE – ______ – _____ mgkg
ONSET - _______.
DURATION – _____ – ____ mins.
DOSE – 0.45 – 0.6 mgkg
ONSET - 60 secs.
DURATION – 30 – 40 mins.
Rocuronium
METAB. – Eliminated _________ by liver.
Reversed by __________
unchanged
Sugammadex
_______________ Can replace suxamethonium for rapid sequence induction
Rocuronium
Sugammadex can be given immediately after rocuronium
T/F. With scenario
T
16mg/kg
e.g in cases of failed intubation
Further classification of MRs
ONSET
Rapid – ___________,___________
Intermediate- ______,______,________,________,__________
Delayed – ____________.
Suxamethonium (30s), Rocuronium (60s)
Atracurium, Mivacurium, Pancuronium, Pipecuronium,Vecuronium.
Doxacurium
Further Classification of MRs
DURATION
Ultra- short - ___________
Short acting – ____________.
Intermediate – __________, __________, __________.
Long - __________, __________, __________.
Ultra- short - Suxamethonium
Short acting – Mivacurium.
Intermediate – Atracurium, Vecuronium, Rocuronium.
Long - Pancuronium, Doxa, Pipe.
Reversal :
________________/________________
Reversibly bind to enzyme leading to deactivation → ↑ Ach conc at NMJ → ↑ Ach at Nicotinic and Muscarinic Sites.
______________
Acetylcholinesterase Inhibitors /Anti Cholinesterase.
Neostigmine
_______________- can reverse rocuronium
Sugammadex
Effects Of Anticholinesterase:
______cardia
______________
↑ __________
CNS ________
↑ _________
↑ Glandular secretions.
Muscarinic effects antagonised by _____________
Brady; Bronchospasm
Secretions; agitation
Peristalsis; anticholinergics
Muscarinic effects antagonised by anticholinergics - _________,________.
Atropine
Glycopyrrolate
Effects Of Anticholinesterase:
Neostigmine- ______ mg/kg.
_____-_____ mg max.
Atropine - ____mg/ 1 mg neostigmine. Glycopyrrolate -_____ mg/ 1 mg neostigmine.
0.04
2.5 – 5
0.5 ; 0.25
In reversal, Anticholinergics given after neostigmine
T/F
F
Anticholinergics given before or with Neostigmine BUT never after
Clinical Assessment of Reversal:
Sustained _________ x ____ secs → < 30% blk
Ability to
___________
___________
___________
Maintain sustained ___________.
Achieve adequate ______ - look at the reservoir bag
Achieve adequate ______- 15mls/kg.
Achieve inspiratory press _____cmH2O
head lift x 5 secs
Open mouth.
Protrude tongue.
Cough
hand grip.
VT
VC
20cmH2O
D-Tubocurarine :
1935
_____________ compound.
Dose _____ – _____mg/kg.
Onset ___-____ mins.
Duration – ____-____mins.
Dose 0.5 – 0.6 mg/kg.
Onset 3 – 5 mins.
Duration – 30 - 50 mins.
D-Tubocurarine :
Effects –
Histamine release +++ →Broncho______
- Vaso________. - ____tension
________ blockade.
Severe _______________.
Metabolism. - Excreted unchanged by _______.
Uses - ______________ anaesthesia.
spasm.; dilatation; Hypo
Ganglion; anaphylaxis
kidneys
Hypotensive
