Cholinergics III, neuromuscular agents

Question 1

What is the effect of ephedrine on skeletal muscle contraction?

Answer 1

Leads to stronger contractions, reason unknown

Question 2

What is the effect of skeletal muscle denervation? (2)

Answer 2

Increased sensitivity of N2 receptors to Ach

Muscle atrophy

Question 3

What are 3 examples of N2 receptor competitive antagonists provided? What is the clinical use?

Answer 3

Curare
Cisatracurium
Vecuronium
Cause the relaxation of skeletal muscle

Question 4

What is the single example of a non-competitive depolarizing agent provided?

Answer 4

Succinylcholine

Question 5

How do depolarizing agents work? What are potential side effects? (2)

Answer 5

First contract muscle, then persistent relaxation
Can cause excess K+ release, leading to cardiac arrest
Can cause extraoccular muscle ctx, eye damage

Question 6

Where along the muscle is the muscle end plate located?

Answer 6

In the center

Question 7

What is the effect if AchE inhibitors on Ach concentrations in the NMJ? Which of these agents is the first line treatment for myesthenia gravis?

Answer 7

Increased Ach concentration

Neostigmine

Question 8

What is denervation supersensitivity? Can it be reversed?

Answer 8

If skeletal muscle loses its nerve, the endplate dissipates, leading to reduced amount of Ach need to trigger ctx because of upregulation of AChR all over the muscle
Can be reversed by reinnervation

Question 9

Which type of muscle atrophies in response to denervation? What type of muscle retains activity?

Answer 9

Skeletal muscle

Smooth muscle

Question 10

Neuromuscular blocking agents usually have [secondary/tertiary/quaternary] nitrogens and are thus have [great/okay/poor] lipid solubility

Answer 10

Quaternary

Poor

Question 11

Two major uses for neuromuscular blocking agents are _

Answer 11

Anesthesia adjunct

Muscle relaxant

Question 12

What is the mechanism of action of the non-depolarizing neuromuscular inhibitors?

Answer 12

They out-compete Ach, blocking the opening of AChR (sodium channels) in the closed position

Question 13

How does an AchE inhibitor interact with non-depolarizing neuromuscular inhibitors? What are 2 AChE inhibitors used for this purpose?

Answer 13

Blocks the hydrolysis of Ach, increasing ACh effective concentration, aiding it in competition against the neuromuscular inhibitors
Neostigmine, Edrophonium

Question 14

In what order is muscle function lost following administration of non-depolarizing inhibitors? In what order is it regained?

Answer 14

Small rapidly moving muscles
Trunk, neck, limbs
Intercostals and diaphragm
Reverse order regained

Question 15

Among the non-depolarizing neuromuscular inhibitors, which of the following are long, intermediate and short acting? d-tubocurarine, cisatracurium, vecuronium, pancuronium, mivacurium

Answer 15

Long - d-tubo, pancuronium
Intermediate - Cis and vec
Short - miva

Question 16

Which of the non-depolarizing neuromuscular inhibitors fall into the benzylisoquinolines? What are characteristics of this group? (d-tubocurarine, cisatracurium, vecuronium, pancuronium, mivacurium)

Answer 16

d-tubocurarine, cisatracurium, mivacurium (curiums)

No vagolytic block (i.e. no tachycardia), but histamine release

Question 17

Which of the non-depolarizing neuromuscular inhibitors fall into the ammonio-steroids? What are characteristics of this group? (d-tubocurarine, cisatracurium, vecuronium, pancuronium, mivacurium)

Answer 17

pancuronium, vecuronium, rocuronium (curoniums)
vagolytic block (tachycardia), but no histamine release

Question 18

What is the only example of depolarizing neuromuscular inhibitor provided? How does it function?

Answer 18

Succinyl choline

It depolarizes skeletal muscle, then causes persistent inhibition

Question 19

Succinylcholine in metabolized by _

Answer 19

Plasma cholinesterase

Question 20

What is a phase 1 block? Phase 2?

Answer 20

Phase 1 - depolarized membrane, therefore unresponsive

Phase 2 - rare, repolarized membrane, but desensitized to ACh stimulation

Question 21

What are the contraindications of the non-depolarizing neuromuscular blockers? (4)

Answer 21

Liver or renal dysfunction
Can cause / worsen hypotention (N1 receptor block, histamine release)
Certain Antibiotics
Myesthenia gravis patients

Question 22

What are the contraindications of the depolarizing neuromuscular blockers? (4)

Answer 22

Mutant plasma cholinesterase
Organophosphate poisoning (reduced functional plasma chE)
Heart failure, burns, trauma, neuromuscular disease patients (increased K+ release can cause cardiac arrest)
Patients suceptible to anterior occular chamber damage

Question 23

What is the dibucaine test?

Answer 23

A test to determine whether patients have mutant plasma cholinesterase that won’t metabolize succinylcholine

Question 24

AchE inhibitors can be readily used to reverse the effects of competitive on-depolarizing neuromuscular blockers. What are the two examples provided?

Answer 24

Edrophonium

Neostigmine

Question 25

AchE inhibitors can be readily used to reverse the effects of competitive on-depolarizing neuromuscular blockers. Why are these drugs usually coadministered with atropine?

Answer 25

Because they will also increase ACh in the non-neuromuscular synapses (e.g. muscarinics), therefore Atropine will block overstim. of cholinergic system

Question 26

Why is it not necessary to actively reverse the effects of succinylcholine? When can this backfire?

Answer 26

It is rapidly hydrolized by plasma cholinesterase

When there is a genetic abnormality affecting plasma cholinesterase

Question 27

What are two scenarios that can produce prolonged phase 2 type inhibition of neuromuscular transmission?

Answer 27

Inhibited plasma cholinesterase (OP poisoning)

Genetically defective plasma cholinesterase (prolonged succinyl choline activity)

Question 28

What is a distinguishing characteristic of the motor endplate regarding synapse location? Where is AChE located? What receptor subtype would you find here?

Answer 28

The synapse is located in the center of the muscle fibers
Concentrated in the folds of the endplate
N2 (Nm)receptors