Test 1: lecture 17 Flashcards
what kind of receptors are on the end of nerves to skeletal muscle?
nicotinic ACh receptors
(ion channel that binds to 2 ACh to allow Na in and K out)
what happens in nicotinic receptor?
ion gated ACh receptors (found at skeletal muscle and preganglionic junctions (both sym and para))
two ACh will bind, opens gate and Na flows in and K flows out
what is the major mechanism of catechol action termination vs ACh termination?
ACh is broken down in the cleft by AChE
NE is reuptaken into the nerve by plasma membrane transporters
what is the limiting factor for ACh reaction?
amount of choline available
ACh is broken apart and choline needs to be brought back into the cell by plasma membrane transporter
what is the rate limiting step for catecholamine ?
amount of tyrosine hydroxylase is available
Ltyrosine(TH)→ DOPA
what happens to nicotinic receptors if you leave ACh attached for long periods?
desensitized
can’t open again for awhile → flaccid paralysis
If only 1 -3 vesicles are released you generate a —
miniature endplate potential (MEPP)
(just a little blip but not enough to cause depolarization/ muscle contraction)
when to use neuromuscular blocker?
makes muscles relax:
for intubation
for surgery
ortho- to reduce fractures
electroshock- prevent muscle cramps to cause bones to break
important usage considerations of neuromuscular blockers
just relax muscles, can still feel pain and know what is happening
can cause respiratory muscle paralysis so need to mechanially ventilate
two types of neuromuscular blockers
(1) Nondepolarizing competitive blockers
(2) Depolarizing blockers
The block by a competitive antagonist can ALWAYS be overcome by —
increasing the concentration of agonist
(which ever with the largest concentration wins, can go back and forth on who is bound to receptor)
what are three nondepolarizing competitive blocker?
d-tubocurarine (Curare)
pancuronium (Pavulon)
atracurium (Tracrium)
will bind but nothing happens in muscle (antagonist/blockers)
can overcome block if you add a bunch of agonists
The agonist curve shift — in a parallel fashion in presence a fixed concentration of the competitive antagonist
rightward
will take more agonist to activate if there is antagonist present (will have a higher Kd)
how to increase agonist at a nicotinic receptor that is blocked by nondepolarzing competitor?
ion channel is flooded with competitive antagonist
need to increase agonist/ACh to overcome antagonist
can increase nerve stimulation
can inhibit AChE→this leads to high levels and during of ACh in the cleft
if you give anti- AChE it will cause increase of ACh everywhere, if you are only trying to effect Nm what can you do?
Nm are muscular= nicotinic ACh receptors
other ACh receptors are muscarinic receptors found throughout the body at pre ganglionic(sym and para) as well as at sym post ganglion to sweat galnds and para post to smooth muscle, cardiac muscle and gland cells
To block all the ACh to these other ACh places can give muscarinic blocker such as atropine
d-tubocurarine (tubarine)
curare= nondepolarizing blocker of nicotinic ACh receptor
stops ACh from activating muscle cell
arrow poison- safe to eat, no BBB cause 2+ charge,
IV causes drug to move to NMJ, short onset, long duration
not metabolized= pooped(bile) and peed out
progressive paralysis small to big muscles
histamine release causes transient hypotension
rapid dose of — can cause histamine release resulting in transient hypotension
d-tubocurarine
(curare= competitive block at NMJ for ACh= nicotinic receptors)
cause progressive paralysis
dart poison
binds to nicotinic (ACh) receptors at NMJ and stop depolarization/contraction of muscles
found at NMJ, symp and para preganglionic junctions, and in brain
pancuronium (Pavulon)
competitively blocks/antagonist for nicotinic ACh receptors at the NMJ
made from steroid
long duration
NO histamine release (d-tubocurarine does)
metabolized a little in the liver
binds to nicotinic (ACh) receptors at NMJ and stop depolarization/contraction of muscles
atracurium (Tracrium)
nondepolarzing blocker= competitively blocks/antagonist for nicotinic ACh receptors at the NMJ
can easily be hydrolyzed by plasma esterases because of two ester bonds
medium duration
can use in animals with liver disease
small histamine release
binds to nicotinic (ACh) receptors at NMJ and stop depolarization/contraction of muscles
difference between non-depolarizing blockers and depolarizing blockers of nicotinic Nm blockers
non-depolarization: can be overcome by adding more ACh
depolarizing: can not be overcome
nondepolarizing: competitive blocker/antagonist: d-tubocurarine (Curare), pancuronium (Pavulon), atracurium (Tracrium)
depolarizing: succinylcholine (Anectine)
succinylcholine (Anectine)
depolarizing blocker of nicotinic Nm receptors
binds to ACh Nm receptors at NMJ and stops depolarization/contraction of muscle
short onset, and short duration (duration changes with species)
will open and close channel causing fasiciculations
depolarizing blocker= can NOT reverse effect with increased ACh, need to just wait it out
if you add ACh it will just desensitize the receptors that are left and make it worse
what happens if you use anti-AChE after using succinylcholine (anectine)
it will make paralysis worse
anti-AChE= ACh will last longer and there will be more of it
succ binds to nicotonic receptor and is stuck there for several minutes (cause fasicululations), if you add more ACh it will bind to other Nicotinic receptors but will bind too long and cause desentization of the remaining receptors
if you give anti AChE with competitive blocker of Nm what will happen
anti AChE= more ACh= will reverse the block
muscle will contract
competitive Nm blockers are: d-tubocurarine, pancuronim, atracurium
what happens to motor end plate with competitive vs depolarizing blocker?
nicotinic ACh receptors at the NMJ
competitive: binds and no depolarization of cell= paralysis
can be overcome by increasing ACh in the cleft
depolarizing= will cause fasiculations (open and close channel) then leads to paralysis, can not be undone, just need to wait. if you add ACh it makes it worse because excess ACh will desensitize the remaining Nm channels
nondepolarizing: competitive blocker/antagonist: d-tubocurarine (Curare), pancuronium (Pavulon), atracurium (Tracrium)
depolarizing: succinylcholine (Anectine)
