Test 1: lecture 17

Question 1

what kind of receptors are on the end of nerves to skeletal muscle?

Answer 1

nicotinic ACh receptors
(ion channel that binds to 2 ACh to allow Na in and K out)

Question 2

what happens in nicotinic receptor?

Answer 2

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

Question 3

what is the major mechanism of catechol action termination vs ACh termination?

Answer 3

ACh is broken down in the cleft by AChE

NE is reuptaken into the nerve by plasma membrane transporters

Question 4

what is the limiting factor for ACh reaction?

Answer 4

amount of choline available

ACh is broken apart and choline needs to be brought back into the cell by plasma membrane transporter

Question 5

what is the rate limiting step for catecholamine ?

Answer 5

amount of tyrosine hydroxylase is available

Ltyrosine(TH)→ DOPA

Question 6

what happens to nicotinic receptors if you leave ACh attached for long periods?

Answer 6

desensitized

can’t open again for awhile → flaccid paralysis

Question 7

If only 1 -3 vesicles are released you generate a —

Answer 7

miniature endplate potential (MEPP)

(just a little blip but not enough to cause depolarization/ muscle contraction)

Question 8

when to use neuromuscular blocker?

Answer 8

makes muscles relax:

for intubation
for surgery
ortho- to reduce fractures
electroshock- prevent muscle cramps to cause bones to break

Question 9

important usage considerations of neuromuscular blockers

Answer 9

just relax muscles, can still feel pain and know what is happening

can cause respiratory muscle paralysis so need to mechanially ventilate

Question 10

two types of neuromuscular blockers

Answer 10

(1) Nondepolarizing competitive blockers
(2) Depolarizing blockers

Question 11

The block by a competitive antagonist can ALWAYS be overcome by —

Answer 11

increasing the concentration of agonist

(which ever with the largest concentration wins, can go back and forth on who is bound to receptor)

Question 12

what are three nondepolarizing competitive blocker?

Answer 12

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

Question 13

The agonist curve shift — in a parallel fashion in presence a fixed concentration of the competitive antagonist

Answer 13

rightward

will take more agonist to activate if there is antagonist present (will have a higher Kd)

Question 14

how to increase agonist at a nicotinic receptor that is blocked by nondepolarzing competitor?

Answer 14

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

Question 15

if you give anti- AChE it will cause increase of ACh everywhere, if you are only trying to effect Nm what can you do?

Answer 15

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

Question 16

d-tubocurarine (tubarine)

Answer 16

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

Question 17

rapid dose of — can cause histamine release resulting in transient hypotension

Answer 17

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

Question 18

pancuronium (Pavulon)

Answer 18

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

Question 19

atracurium (Tracrium)

Answer 19

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

Question 20

difference between non-depolarizing blockers and depolarizing blockers of nicotinic Nm blockers

Answer 20

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)

Question 21

succinylcholine (Anectine)

Answer 21

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

Question 22

what happens if you use anti-AChE after using succinylcholine (anectine)

Answer 22

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

Question 23

Answer 23

Question 24

Answer 24

Question 25

if you give anti AChE with competitive blocker of Nm what will happen

Answer 25

anti AChE= more ACh= will reverse the block

muscle will contract

competitive Nm blockers are: d-tubocurarine, pancuronim, atracurium

Question 26

what happens to motor end plate with competitive vs depolarizing blocker?

Answer 26

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)
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depolarizing: succinylcholine (Anectine)