Lecture 2 Neuromuscular/Ganglionic Blockers

Question 1

Ganglionic blockers are ______ receptor _____

Answer 1

nicotinic, antagonists

Question 2

2 important ganglionic blockers to know:

Why are these not commonly used?

Answer 2

trimethaphan, mecamylamine

they block the entire ANS (ie block pupillary reflex and baro-receptor reflex)

Question 3

Uses of trimethaphan:

Use of mecamylamine:

Answer 3

trimeth = hypotension for surgery

mecamylamine = tourette’s, smoking cessation, severe hypertension

Question 4

In general, the ____ tone is stronger than the ____ tone. What is the exception to this and why does this exception occur?

Answer 4

parasympathetic, sympathetic;

smooth muscles of vascular tone (ie regular vasoconstriction), because the M3 receptors are not innervated

Question 5

ganglionic blockade results in ____ and ____

Answer 5

vasodilation, tachycardia

Question 6

Therapeutic use for neuromuscular blockers?

Answer 6

surgery and intubation

Question 7

What was the first clinically used neuromuscular blocker, and what was the active component of it?

Answer 7

curare

d-tubocurarine

Question 8

Without blockade, how many twitches of the thumb should be seen with the “Train of 4 test”? The train of 4 ratio is the ratio of the ____ twitch to the ____ twitch

Answer 8

4; 4th, 1st

Question 9

Sedation is said to be complete with a TOF ratio of ___, or ____ twitches out of 4 impulses.

Answer 9

.25; 1-2

Question 10

Recovery to a TOF ratio of ___ is needed before extubation. A ratio of ___ is for “full clinical recovery”

Answer 10

.7;

.9

Question 11

(Depolarization/Non-depolarizing) blockers will show a decrease in response strength between subsequent stimuli, called fade.
This is absent in (non-depolarizing or depolarizing?) blockers until a TOF ratio of 0.3 is reached. This is called phase ____

Answer 11

depolarizing,
non-depolarizing

II

Question 12

No additional dose of blocker should be given if __ twitches are observed with the TO4 test

Answer 12

no

Question 13

Sequence of muscle paralysis by curare/neuromuscular blockers:

Answer 13

eye/speech–>extremities/limbs –> intercostals –> diaphragm

ie outside in. mimics GBS

Question 14

_____ is a depolarizing NAchR agonist. It is ____ acting as it is rapidly metabolized by _____

Answer 14

Succinylcholine (Sux);

short, butyrylcholinesterase

Question 15

Sux should be avoided in patients with _____ as additional release of ____ can cause cardiac arrest

Answer 15

hyperkalemia,

potassium

Question 16

Specifically, Sux inhibits ____ of the NAchR receptor, preventing further action potentials from occuring. ___ use of the agonist will give a muscle twitch

Answer 16

repolarization;

first

Question 17

Pancuronium./vecuronium/atracurium are _____ neuromuscular blockers that are ______ of Nicotinic receptors

Answer 17

non-depolarizing;

competitive antagonists

Question 18

Non-depolarizing neuromuscular blockers are easily ____ and have a ____ duration of action.

Answer 18

reversable; long

Question 19

What is a short acting non-depolarizing neuromuscular blocker?

Answer 19

trimethaphan

Question 20

reverseal of non-depolarizing blockade:

1. use of an AchE inhibitor such as _____. It increases levels of Ach to compete with the antagonist.
2. Use of ____ which binds and sequesters pancuronium

Answer 20

neostigmine,

sugammedex

Question 21

AchE inhibitors rely on the presence of Ach. ie, they have little effect on the function of ____ receptors located in ____ ____

Answer 21

M3; blood vessels

Question 22

AchE is located in ____. BuChE is located in ____ and prefers _____ and other local anaesthetics such as procaine.

Answer 22

synapses;

plasma, succinylcholine

Question 23

Three classes of AchE inhibitors:

Answer 23

carbamates, organophosphates, quarternary ammonium alcohols

Question 24

Carbamates can be tertiary or quarternary amine groups. they temporarily create a ____ ____ with AcheE, but it is rapid and reversible

Answer 24

covalent bond

Question 25

Physostigmine is a _____ amine. Does it enter the CNS? What is it used for?

Answer 25

tertiary; yes; block atropine Overdose, glaucoma, alzheimers.

Question 26

Neostigmine and pyridostygmine are _____ amines. They (do/do not) enter the CNS. They are used for _____ _____, _____ ileus, and reversal of ____ ____

Answer 26

quarternary;
do not;
myasthenia gravis, post-operative; neuromuscular blockade

Question 27

Neo vs Pyrdiostigmine: ____ is orally bioavailable has fewer side effects, and has a longer duration of action

Answer 27

pyridostigmine

Question 28

Organophosphates such as isofluorophate and echothiophate can rarely be used in treatment of _____. They bind ___ via ____ bonds to AchE and are very long lasting.

Answer 28

glaucoma;

irreversibily, covalent

Question 29

Nerve gas ( _____) and insecticides such as _____ irreversibly bind AcheE

Answer 29

sarin, parathion

Question 30

Treatment of organophsphate poisoning:
_____ is the antidote.
_____ can help treat the symptoms as it has a fast onset

Answer 30

pralidoxime,

atropine

Question 31

Aging of organophosphates is due to _____ of the covalent bond. _____ prevents aging and regenerates AchE

Answer 31

hydrolysis;

pralidoxime

Question 32

Acetycholine Esterase Inhibitor Poisoning: DUMBBELS
D= \_\_\_\_
U = \_\_\_\_\_\_\_\_\_\_
M = \_\_\_\_\_\_\_
B = \_\_\_\_\_\_\_\_\_

Answer 32

diarrhea,
urination,
miosis,
bronchospasms

Question 33

DUMBBELS of AchE Inhibtor poisoning:
B =
E = 
L =
S = 
S =

Answer 33

bradycardia;
excitation of skeletal muscle/CNS (most worrisome)
Lacrimation;
Sweating
Salivaiton

Question 34

Edrophonium is a_______ ammonium alcohol that binds non-covalently and is ____ acting. It is used to diagnose ____ ____

Answer 34

quarternary; short

myasthenia gravis

Question 35

Myasthenia gravis:
Antibodies against?
Effect of exercise on symptoms?
Effect of edrophonium?

Answer 35

Nicotinic receptors at NMJ;
makes it worse;
improves symptoms

Question 36

Lambert Eaton:
Antibodies against?
Effect of exercise on symptoms?
Effect of edrophonium?

Answer 36

calcium channels;
improves muscle strength;
no effect

Question 37

negative edrophonium test is seen in ____ crisis. symptoms are due to ______ of receptors, leading to paralysis

Answer 37

cholinergic; overstimulation

Question 38

With parasympathetic drugs, watch for exacerbation of _____, _____, and ____ ____

Answer 38

asthma, COPD, peptic ulcers

Question 39

NE is produced in the _____.

Ach is produced in the _____

Answer 39

locus ceruleus;

nucleus basalis of meynert + medial septal nuclei

Question 40

three drugs used to treat alzheimer’s

do these slow progression of disease?

Answer 40

donepezil, rivastigmine, galatamine; no, just help manage symptoms

Question 41

____ binds to the anionic site of the AchE Inhibitor, preventing Ach binding.

Answer 41

donepezil

Question 42

_____ and ____ are reversible competitive AchE inhibitors. they ____ effectiveness as the disease progresses

Answer 42

galantamine, rivastigmine;

lose