Pharm Katzung Ch 27

Front 1

what are the 2 types of NML blockers?

Back 1

nondepolarizing = antagonistic competitive

depolarizing = agonist

Front 2

what is the mechanism for nondepolarizing NMJ blockers?

Back 2

competition with Ach
prevent depolarization of receptor

Front 3

what is the structure of the post-synaptic nicotinic receptor?
subunits?
domains?

Back 3

5 subunits
α2βδγ
each subunit has 4 domains
2 binding pockets δα & αβ

Front 4

role of Ach receptor on pre-synaptic motor axon terminal?

Back 4

moves vesicles to synaptic membrane for release

Front 5

compare kidney vs liver excretion of non-de-polarizing NM blockers

1/2 life
duration of action

Back 5

kidney >> 1/2 life, duration of action

liver << 1/2 life, duration of action
metabolites can accumulate

Front 6

how are NM blocking drugs administered and why?

Back 6

give parenterally bc inactive orally

highly polar compounds with poor lipid solubility due to quaternary N

don't cross membranes so stay in plasma --> vol of distribution about = blood vol

Front 7

for nondepolarizing NM blockers
what is the relationship between potency, onset and duration of action

Back 7

least potent have fastest onset and shortest duration of action

Front 8

what is the relationship between end plate potential (epp) and Ach released?

Back 8

magnitude of epp is directly related to amount of Ach released

if small, impulse not generated

if large, more Ach released and adjacent muscle membrane depolarizes --> action potential propagated along entire fibre

Front 9

what is the structure of succinylcholine?

Back 9

2 Ach molecules linked end to end

Front 10

what is the duration of succinylcholine and why?

Back 10

short duration of action due to rapid hydrolysis by cholinesterase in the plasma

Front 11

mechanism of action of nondepolarizing NM receptor blocker?

Back 11

binds to the receptor at the same site as Ach and blocks Ach from binding --> prevents opening of the channel

competitive with Ach
antagonistic

Front 12

what is the only clinically useful depolarizing blocking drug?

Back 12

succinylcholine

Front 13

what reverses residual blockade by nondepolarizing NM blockers/muscle relaxants?

Back 13

cholinesterase inhibitors reverse residual blockade

Front 14

how do depolarizing blockers work?

Back 14

occupy the receptor --> the motor end plate --> contraction

then blocks the channel --> desensitize the end plate by causing persistent depolarization --> flaccid paralysis

Front 15

how to cholinesterase inhibitors reverse depolarizing blockers?
phase I vs. phase II

Back 15

phase I = augmentation of phase I depolarizing blockade by cholinesterase inhibitors

phase II - reversal of blockade by cholinesterase inhibitors during phase II depolarizing blockade

Front 16

what is phase I of depolarizing blockade?

Back 16

reacts with the nicotinic receptor to open the channel --> depolarization --> initial twitch --> remains depolarized bc succ not metabolized at the synapse --> flaccid paralysis

Front 17

what is phase II of depolarizing blockade?

Back 17

desensitization
channels act as if closed --> like nondepolarizing block

Front 18

side effects of succinylcholine?

Back 18

- Bradycardia (muscarinic agonist reaction)

- Hyperkalemia - heart rate perturbations.

- Increase intraocular pressure (nicotinic effect on extraocular muscles)

- Post operative muscle pain

Front 19

what happens with continued administration of succinylcholine?

Back 19

Continued administration brings to block (phase II), desensitization of the receptors and delay of recovery