Muscle relaxant drugs (11) Flashcards
To perform anesthesia as a perfectionist, with nothing less than pure anesthesia badassary!!!!!!
Acetylcholine contains a positively charged quaternary ammonium group that attaches to the _________ charged _________ receptors
- negatively
- cholinergic
how is acetylcholine synthesized?
acetyl-Coa + choline —-????—-> acetylcholine (basiaclly what is the enzyme that helps is convert)
choline acetyl transferase
see slide #4 (Muscle relaxant drugs)for the chemical structures it may help
how is acetylcholine metabolised
acetylcholine ——-??????—–> choline + acetic acid (basically what is the enzyme that breaks acetylcholine down?)
cholinesterase
see slide #4 (Muscle relaxant drugs)for the chemical structures it may help
So acetylcholine is rapidy metabolized by acetylcholinesterase into _______ and _____
Acetate and Choline
acetylcholinesterase is also called _________ ___________ or _____ _________
specific cholinesterase or true cholinesterase (just incase he tries to throw a curve ball)
how does acetylcholine work in the neuro muscular junction (NMJ)
1st- Ach is released presynaptically and bindsto the postsynaptic nicotinic receptor
-NEXT- there are 2 alpha subunits on the nicotinic receptor
-LAST(LY)- Na+ channels open when both subunits are occupied by Ach
((((side note this will show why and where the NMBD work and why they block the Na+ channels)))))
(5) main structures of Muscle relaxants
- -ALL are quaternary ammonium compounds ( 4 carbon atoms attached to 1 Nitrogen atom)
- ALLcontain at least 1 ammonium group
- ALL MIMIC ACh to exert relaxant properties
- the POSITIVELY charged quaternary ammonium group is electrostatically attracted to the negatively charged cholinergic receptor
- SCh (a small slender molecule) binds to (both alpha units) and activated ACh receptor
Look at slide 11 in the Muscle relaxant drugs ppt
to see the chemical makeup of vec and pan
mono vs bisquaternary
2main categories of muscle relaxants (don’t over think it)
Depolarizers
non-depolarizers
2 examples of depolarizers (only that we really use I am not even sure if the other is still in use)
- Succinylcholine
- Decamethonium
6 main non-depolarizers ( to become an extra bad badass what is the 7th don’t need to know for test but for knowledge)
Curare Pancuronium veruronium pocuronium atracurium cis-atracurium BONUS --------Mivacurium
what is a special note about Curare
its the origional NDMBD
******************************************* Must know the doses of the following Cis-atracurium Rocuronium Pancuronium Vecuronium
in order per potency (Pink Vagina Can-Always Rebound) Pancuronium-0.08-0.1 Vercuronium-0.08-0.1 Cis-Atracurium- 0.15-0.2 mg/kg Rocuronium- 0.6-1.2 mg/kg
Depolarizers (Sux’s) resemble and mimic ______ at the Ach receptor
Acetylcholine
how do DMBDs work (Sux’s)
- mimic ACh at teh ACh receptor
- cause sustained depolarization rendering the NMJ unable to conduct further impulses which = muscle relaxation
- fasiculations
Sux’s (DMBDs) has how many phases
2
what is a phase I block of DMBDs
sustained opening of receptor channels in depolarized post junctions membrane cannot respond to further ACh
what is phase II block of DMBDs
desensitized repolarized post-junctional membrane remains unresponsive to ACh. (occurs after a large or repeated sux’s doses)
when does phase II blocks occur
After large or repeated doses of sux’s
what is the mechanis that causes phase II blocks
Unknown
Side effects of DMBDs (sux’s)
-the sustained depolarization causes K+ to be releases from cells (remember most K+ is stored in the cell)
Hyperkalemia is an increased risk with Sux’s administration,but this risk is increased with what type of pt’s
Upregulated
the massive K+ release associated with DMBDs (sux’s) is released from where
extra junctional receptors
Sux’s is metabolized by what? and where?
psuedocholinesterase
in the plasma
plasmacholinesterase (what metabolizes sux’s) is also called what
psuedocholinesterase
butyrocholinesterase
Sux’s is metabolized rapidly into ___________ upon injection into the blood, thus only a fraction actually reaches the NMJ
Succinylmonocholine
what accounts for th longer duration of action of depolarizers (sux’s) compared to ACh
b/c depolarizers must diffuse away from the NMJ to the plasma to be metabolized
(kinda of confusing, if you want clarification look at slide 19, basic take home message is that sux’s last longer than ACh)
2 types of psuedocholinesterase deficiency’s
1) Heterozygous atypical
2) Homozygous atypical
what drug would a psuedocholinesterase deficiency affect and why?
Sux’s, b/c thats what metabolizes all DMBDs AKA sux’s
2 things to know about psuedocholinesterase deficiency
Heterozygous atypical
-1 abnormal gene ( way to remember HETER 1 male 1 female)
-prolonged block 20-30 minutes after sux’s administration
(side note occurs 1:50 pts)
2 things to know about psuedocholinesterase deficiency Homozygous atypical
-2 abnormal genes ( way to remember 2 fags= homo)
-prolonged blockake 6-8 hours after sux’s
(side note occurs 1:3000 pts)
which type of psuedocholinesterase deficiency is most common
heterozygous
in relation to psuedocholinesterase deficiency the __________ number represents the percentage inhibition of pseudocholinesterease
Dibucaine
what is DIBUCAINE
a local anesthetic that inhibits normal pseudocholinesterase by 80%, heterozygous by 40-60% and homoxygous by 20%
NDMBDs 3 facts about their distribution
1) highly ionized (low lipophilicity)
2) low volume of distribution (extracellular fluid)
3) do NOT cross the BBB, placental barrier, or GI
Chemical structures of all NDMBDs
J/K see slide 24 ( just look at and see basic make up..
NDMDs action 4 simple steps
- competative antagonism
- binds to ACh receptors (but exert no effect)
- Block action of ACh
- then diffusion away from NMJ site to site of metabolism
NDMBDs duration (not individual just est from ppt slides on all overal ) short, intermediate, long acting
short acting 5-20 min
intermediate acting 25-55 min
long acting 60 min and >
Metabolism of NDMBD
metabolized in Liver Kidney Plasma and spontaneously
how are NDMBDs excreated in active or inactive forms
Both
how does Pregnancy affect PK of NDMBDs
- no change in PK
- UNLESS os MgSO4 (this results in increased potency and duration)
how does temperatire affect NDMBDs
hypothermia causes INCREASED duration of action
how does AGE effect PK of NDMBDs
Vd larger in children
elderly can have longer duration with organ clearance drugs
how does obesity effect PK of NDMBDs
Vd and clearance reduced
Must Know ******************************** SUCCINYLCHOLINE ED 95 mg/kg intubation dose time to intubation duration elimination histamine release
ED 95 mg/kg---0.25 MG/KG intubation dose--1-1.5 MG/KG time to intubation--30-20SEC duration 5-10 MIN elimination -- PLASMACHOLINESTERASE histamine release--YES
Must Know ******************************** PANCURONIUM (pavulon) ED 95 mg/kg intubation dose time to intubation duration elimination histamine release
ED 95 mg/kg --0.07 MG/KG intubation dose--0.08-0.1 MG/KG time to intubation--3-5 MIN duration--80-100 MIN elimination -- 80% RENAL; 20% BILIARY histamine release--NOPE
Must Know ******************************** VECURONIUM (norcuron) ED 95 mg/kg intubation dose time to intubation duration elimination histamine release
ED 95 mg/kg--0.06 MG/KG intubation dose--0.08-0.1 time to intubation--2-3 MIN duration--25-30 MIN elimination-- 20% RENAL; 80% BILARY histamine release-- NO
HINTS ( vec and pan are very similar- dose is the same time to intubate close to the same. main differences is PAN is LONG acting, VEC is INTERMEDIATE acting and eliminatin is inversed)
Must Know ******************************** ROCURONIUM (zemuron) ED 95 mg/kg intubation dose time to intubation duration elimination histamine release
ED 95 mg/kg--0.3 MG/KG intubation dose-- 0.6-1.2 MG/KG time to intubation--1-3 MIN duration--30 MIN elimination --30% RENAL; 70% BILIARY histamine release--NO
Most NDMBDs are metabolised where?
renal and biliary
*** must know**
of the NDMBDs which one should NOT be used with renal failure and why??
- Pancuronium (pavulon)
- b/c 80% excreated by renal
side note from shores (and to make sure that we speak MORE ON A GRADUATE LEVEL per Nancy) how should we say NDMBDs are metabolized in the liver
Say BILIARY TRACT
**must know****
Cis-atracurium (Nimbex) is just like atracurium, but is better and more frequently used why????
has less histamine release
he said that is all we need to know about it
**must know***
shores stated in his lecture that we are not to larn the doseage but must know the following
what is good and bad about Atracurium (tracrium)
- good for kidney and hepatic factors
- bad for histamine release
**must know****
what is important to know about Mivacurium
short acting
has histamine release
no organ clearance (cleared via plasma cholinesterase)
**** must know***
how is Nimbex (cis-atacurium) eliminated
Hoffman elimination
should defiently know this*
what is the relationship between ED95 and intubation dose of muscle relaxants
the intubating dose is 3 xs the ED 95 (you will be pimped) except for VEC and PAN (but close) Roc ED95 0.3 intubating dose 0.6-0.12 (3 times the ED95=0.9 hmm in the middle) Nim ED95 0.05 intibating dose 0.15-0.2 (he said this in class it works 50/50 do what you wish i mean all NDMBDs except Vec and Pan follow this)
what is ED95
a dose causing muscle relaxation suitable for intubation in 95% of the population
** great tip
if someone says how many cc’s of Vec would you give a pt who weighs 70 kg say 7, but then give what rational
most muscle relaxants ( not suxs) can be given in a ratio of 1ml per 10 kg of pt for example
Vec is prepared as 1 mg/ml in bottle and the intubating dose is 0.1 mg/kg so a 70 kg pt would get 7 mg for a dose (0.1 x 70=7mg) so give 7 ml of vec or 7mg
–or Roc 0.9 mg/kg (intubating dose) 70kg x 0.9 mg/kg = 63mg. it comes in 10mg/ml so give 6.3 mls very close to 7
