Neuromuscular Blockade and Paralysis

Question 1

How can muscle force be increased

Answer 1

• The recruitment of multiple muscle fibres

- The summation of increased firing rates of an action potential on a single fibre

Question 2

Why can neuromuscular blockades be useful

Answer 2

Surgery
Preventing muscle contractions (pathology)
Muscle relaxation without general anaesthesia
Cosmetic Surgery

Question 3

What order do neuromuscular blockades affect patients

Answer 3

Extrinsic eye muscles first, small muscles of face and hands, muscles of pharynx then respiratory muscles last

Question 4

How do neuromuscular blockades work

Answer 4

Slow methodical paralysis in skeletal muscle

Question 5

Can those who receive neuromuscular blockades experience pain

Answer 5

Yes.

Question 6

What ways can neuromuscular transmission be blocked

Answer 6

By blocking one of 3 processes

• Neurotransmitter Synthesis/Uptake
• Release
• Receptor

Increasing
- Reuptake

Question 7

How does synthesis blocking of acetyl choline work

Answer 7

By inhibiting the choline carrier that takes choline and acetate back into the cell

**Hemicholonium

Question 8

Clinical Relevance of ACh Synthesis Blocking

Answer 8

Not clinically useful it is slow to activate and slow to reverse

Question 9

How does release blocking of Acetylcholine work to cause a neuromuscular blockade

Answer 9

Alters the exocytosis of the vesicles and blocks neurotransmitter release

Question 10

An example of something that affects neurotransmitter release to cause a Neuromuscular blockade

Answer 10

Botox, Black widow venom (Latrotoxin)

Question 11

Which mechanism to non-/depolarising agents affect

Answer 11

Receptor blocking to cause a neuromuscular blockade

Question 12

How does reuptake increase/Inactivation of Acetylcholine work to cause a neuromuscular blockade

Answer 12

Acetylcholinersterase is inhibited so ACh’s components cannot be taken up

Used to REVERSE Antagonist Block and increase ACh concentration

**Anticholinesterase

Question 13

Example of AChE inhibitor

Answer 13

Physiostigmine

Question 14

What neuromuscular blockade helps treat myasthenia gravis

Answer 14

AChE inhibitors like physiostigmine

**MG is Autoimmune disorder where Ig are created against nAChR Proteins

Question 15

What is Novichok

Answer 15

AChE inhibitor that is used as a toxin and is hard to cure with antidote

Maximises lifetime of ACh and saturates the cleft, causing paralysis

**What was used against Alexie Navalny

Question 16

How do non-depolarising agents work; is it additive

Answer 16

nACh-R competitive Antagonists

**Do not depolarise post synaptic neuron

Question 17

How do depolarising agents work; is it additive

Answer 17

nACh-R Agonists (mimic ACh)

Persistent activation of nACh-R causes inactivation of voltage-gated Na+ channels which can no longer open in response to brief depolarisation

Block is preceded by muscle twitches

**Depolarise post-synpatic neuron

Question 18

Onset and duration of Non-depolarising block and Depolarising block

Answer 18

Non: 3-5 mins onset; 30+ min duration

Depolarising: <1 min onset; approx 5 mins duration **Ideal for intubation

Question 19

What antagonises/reverses non-depolarising blocks

Answer 19

Agents that Depolarise Muscle Membrane
Drugs that increase ACh Release
Anticholinesterases

Question 20

Describe contraction of non-depolarising block in response to stimulation then when exposed to Anti AChE; what else also causes similar effect

Answer 20

(Depolarising block has similar effect to Anti AChE)

Question 21

Describe contraction of Depolarising block in response to stimulation then when exposed to AChE inhibitor

Answer 21

Question 22

3 Non-depolarising blocker examples

Answer 22

Atracurium
Vecuronium
Gallamine

Question 23

2 Depolarising blocker examples

Answer 23

Suxamethonium

Dexamethonium

Question 24

2 AChE inhibitor examples

Answer 24

Physiostigmine

Neostigmine

Question 25

Which class of Neuromuscular Blockade drugs are addictive

Answer 25

Receptor Blockers

Non-depolarisign and Depolarising Agents

Question 26

Qualitatively compare the onset/duration of Non-Depolarising NM Blockades vs Depolarising Agents

Answer 26

Non-Depolarising has slower onset & Longer Duration than Depolarising which has rapid onset and offset

Question 27

Which Receptor Blocking class of blockade are not reversed by AntiAChE Drugs

Answer 27

Depolarising Agents are not affected by Anti AChE Drugs while Non-Depolarising agents are