Lecture 12: Muscle Relaxants and Local Anesthetics

Question 1

botulinium toxin

Answer 1

prevents release of ACh (no synaptic vesicle fusion)
- adverse effects may include some anti-cholinergic FX

Question 2

alpha-latrotoxin

Answer 2

from black widow
- promotes Ach release and leads to depletion of ACh stores

Question 3

bungarotoxins

Answer 3

alpha - irreversibly binds to and blocks the nAChRs at the NMJ (paralysis)

beta - prevents release of ACh from motor nerve endings

Question 4

curare

Answer 4

D-tubocurarine is active ingredient in curare which causes non-depolarizing block of nAChRs
- not available orally, so on the tip of poison arrows it’ll paralyze you but if you eat the animal you kill with the poison arrows it won’t affect you.

Question 5

histrionicotoxin

Answer 5

binds and blocks nAChR (open channel blocker)

Question 6

pharmacology of D-Tubocurarine

Answer 6

• given parenterally (no bioavailability)
• poor membrane penetration (which is why you can’t give orally)
• excreted in the urine unchanged
• blockage lasts 20 min - 2 hours
• onset of 2-3 minutes (too slow for intubation)
• causes BP drop and histamine release

Question 7

pancuronium

Answer 7

similar MOA to D-tubocurarine (will cause non-depolarizing block of nAChR)
- also blocks M2 AchRs which leads to increases in HR (agonism of M2 leads to decreased HR meaning antagonism causes increased HR)
- also blocks NE uptake - further increases in HR and vasocontriction

used for general anesthesia and to facilitate mechanical ventilation

adverse FX: CV actions, slow onset (3 min) and duration (86 min)

basically it’s the same as curare except it doesn’t cause an allergic reaction

Question 8

vercuronium

Answer 8

nondepolarizing NMJ blocker
- less potent at M2 ACh R

Question 9

Rocuronium

Answer 9

nondepolarizing NMJ blocker
- less cardiac effects, doesn’t antagonize M2 Rs in the heart
- rapid onset with moderate duration

Question 10

What kind of block does sugamadex reverse?

Answer 10

Non-depolarizing blocks of the NMJ by rocuronium (also vercuronium a bit)
- within 8 min, sugamadex will mop up all the rocuronium and reverse the block

Question 11

Neostigmine, physostigmine, and edrophonium are all…
what are they used for?

Answer 11

AChE inhibitors
- they will reverse a non-depolarizing block by allowing more ACh to accumulate in the synapse and out-compete the blocker

used after surgery to reverse the block

can also be used symptomatic treatment of myasthenia gravis

Question 12

interaction of nondepolarizing NMJ blockers with calcium channel blockers and amino glycoside antibiotics like streptomycin

Answer 12

calcium channel blockers - increase the block of nondepolarizing (competitive) and depolarizing blockers

amino glycosides decrease ACh release from cholinergic fibres (synergy with competitive blockers)

Question 13

Depolarizing NMJ blockers (2)

Answer 13

decamethonium
succinylcholine
(actually bind the nAChR and allow cation influx)

Question 14

Difference in metabolism between ACh and Succinylcholine

Answer 14

ACh is metabolized by AChE while sucicnylcholine is only metabolized by plasma cholinesterase, which isn’t in the NMJ at high conc.

Question 15

How do you treat rare malignant hyperthermia associated with succinylcholine

Answer 15

dantrolene - stops calcium release from SR

Question 16

Myasthenia gravis
what is it and what are diff ways to treat it

Answer 16

low concentrations of nAChR (no change in ACh or AChE at NMJ)

treat with
- AChE inhibitors like pyridostigmine with adjunct atropine to block increased incidence of muscarinic effects
- corticosteroids like prednisone to suppress immune system
- thymus removal

Question 17

How does amide or ester linkage affect metabolism of local anesthetics?

Answer 17

amide link - longer half life, hepatic metabolism

ester link - shorter half life, AChE will break it down (think of the esteratic site of AChE)

Question 18

Local anesthetics with either ester or amide linkage (2 from each)

Answer 18

ester - procaine, tetracaine

amide - lidocaine, bupivacaine

Question 19

how does addition of epinephrine affect admin of local anesthetic

Answer 19

local epi will constrict small blood vessels in the skin and thus localize the drug to a specific area - reduce blood flow away from the site

Question 20

methemoglobinemia

Answer 20

oxidation of hemoglobin to methemoglobin by “caine” oxidizing agents
- can be reversed by methylene blue (electron donor to reduce the hemoglobin back)

Question 21

How does ionization affect local anesthetics

Answer 21

if it’s charged it can’t diffuse away