Nmj

Front 1

what happens to most Ach @ NMJ?

Back 1

degraded by AChE on basal lamina

Front 2

location of Ach receptors @ NMJ?

Back 2

cocentrated nearest to nerve ending, some on extrasynaptic membrane

Front 3

role of NA channels @ NMJ?

Back 3

voltage amplifiers

Front 4

what happens to AChR when muscle is denervated?

Back 4

#s increase along muscular membrane

Front 5

structure of AChR?

Back 5

5 subunits- alpha are all identical, beta turns to epsilon after infancy

Front 6

activation of NMJ AChR?

Back 6

receptor closed in basal state -> Ach binds 1 alpha unit --> another Ach binds other alpha unit ->some receptors open -> ions flow through -> receptor is desensitized -> receptor closes -> Ach comes off and degraded by AChE

Front 7

what is succinylcholine?

Back 7

depolarizing neuromuscular blockers-muscle relexer

Front 8

how does succinylcholine work?

Back 8

structure= 2 Ach bound together. Binds and activates AChR but is not degraded by AChE= prolonged desensitization of AChR and NA channels, large release of potassium

Front 9

how is sux metabolized?

Back 9

it diffuses away from NMJ by hydrolysis and then degraded by butyrylcholinesterase

Front 10

what can prolong the duration of Sux?

Back 10

abnormal butyrylcholinestarase (requires renal elimination); liver dx, pregnancy, renal failure

Front 11

clinical uses of Sux?

Back 11

intubation; brief muscle relaxation for short surgery

Front 12

side effects of Sux?

Back 12

buscle pain, bradycardia (cardiac arrest-mAChR), hyperkalemia (w/ denervation injury), increased pressure, malignant hyperthermia, masseter muscle spasms

Front 13

contraindications to sux?

Back 13

absolute- malignant hyperthermia, major denervation injury more than 24 hours; relative- children, hx of atypical butirylcholinesterase, increased pressure, existing hyperkalemia

Front 14

pharmacokinetic profile of Sux

Back 14

very rapid onset (1 min), short duration(5-10 min)

Front 15

name the non-depolarizing NMJ blockers? Basic mechanism?

Back 15

benzylosoquinoliums, ammonio-steroids, curare-like alkaloids; competitive antagonist for Ach ( can be overcome w/ high concentration)

Front 16

route of administration of NMJ blockers?

Back 16

IV

Front 17

side effects of non-depolarizing NJMJ>

Back 17

histamine release, tachycardia

Front 18

describe train of 4?

Back 18

essentially teslls us how many spare receptors there are. When a nondepolarizing block is present, there are less spare receptors so contraction diminishes w/ subsequent stimulation

Front 19

4 clinical signs of return of adequate NMJ fxn?

Back 19

head lift > 5 sec, raise leg and hold, Negative inspiratory force > 50, large tidal volumes

Front 20

how does the acetylcholinesterase work?

Back 20

histidine site and seritne site interact -> oxygen is nucleophilic --> choline of Ach bine anionic site -->oxygen attacks acetyl of Ach --> acetylated enzyme and reased choline --> water deacytlated --> enzyme is restored

Front 21

Edrophonium

Back 21

ACHE inhibitor, competitive inhibitor that prevents Ach from binding

Front 22

neostigmine

Back 22

AChE inhibitor, covalently binds to AChE forming a carbamylated enzyme that water has a hard time restoring enzyme

Front 23

DFP

Back 23

AChE inhibitor; binds AChE and can't be hydrolyzed =AChE has to be resynthesized; irreversible organophosphate

Front 24

route of AChE inhibitors?

Back 24

physostigmine- PO, quaternary ammonium drugs -PO (poorly), organophosphorus- all routes

Front 25

Metabolism of AChE inhibitors

Back 25

Carbamate inhibitors like neostygmine= by hydrolysis via plasma esterase; organophosphates like DFP by A-esterase then renal excretion

Front 26

Physiological effects of AChE inhibitors are mainly due to what?

Back 26

increases of Ach at muscarinic effectors

Front 27

Physiologic effects of AChE inhibitors?

Back 27

muscle fiber fibrilation then depolarizing block (like sux), increased parasympathetics and sweating, increased bonciolar tone, ceizures, hypotension

Front 28

treatment for toxicity due to AChE inhibitors?

Back 28

atropine (for bradycardia); pralidoxime for organophosphate poisoining (hydrolyzes)

Front 29

uses of AChE inhibitors?

Back 29

reversal of non-depolarizing blockade(competitive), pee/get gut moving, reduce intraocular pressure, MS, alzheimers (CNS nicotic receptors), insecticides, nerve gass

Front 30

tensilon test?

Back 30

used when deciding about AChE inhibitors w/ MS, if u give edrophonium (AChE inhibitor) tensile strength will improve in pts w/ fewer spare receptors due to MS