L13 - Muscle Relaxants

Question 1

What are the points involved in the nervous system in muscle contraction?

Answer 1

• signal from brain
• to spinal cord
• motor neuron
• NMJ
• muscle

Question 2

What are the 2 types of muscle relaxants?

Answer 2

• neuromuscular blockers

- spasmolytics

Question 3

What is the difference between the 2 types of muscle relaxant?

Answer 3

neuromusclar blockers
- paralytic agents
- paralyse normal functioning muscles
spasmolytics
- anti-spasmotics
- relax overactive muscles rather than cause paralysis

Question 4

When are the 2 types of muscle relaxant used?

Answer 4

neuromuscular blockers (NMB) used in anaesthesia
spasmolytics used in variety of neurologic conditions 
- act in CNS of muscle

Question 5

What are the process occurring at the NMJ?

Answer 5

• motor neuron AP to NMJ
• release of neurotransmitter (ACh)
• ACh across synaptic cleft to nicotinic receptors on muscle fibre
• ACh receptor activation causes Na+ influx and K+ outflux causing muscle membrane depolarisation
• Ca2+ release causes muscle contraction
• ACh in synaptic cleft removed by aceylcholinesterase (AChE)

Question 6

What are the 2 types of neuromuscular blocker?

Answer 6

• non-depolarising: nicotinic receptor antagonists

- depolarising: cause persistent activation of ACh receptors = excessive depolarisation

Question 7

What is an example of a non-depolarising neuromuscular blocker?

Answer 7

tubocurarine

Question 8

How do non-depolarising NMBs work?

Answer 8

• they are competitive antagonists of ACh at the motor end plate
• must block 70-80% of post-synaptic receptors to block transmission
• has to overcome ‘safety factor of transmission’ ACh is released in excess of what is needed

Question 9

Is the effect of NMB reversible? If yes, how?

Answer 9

NMB effect is reversible

- can be reversed by the addition of aceylcholinesterase inhibitor e.g. neostigmine to increase ACh concentration

Question 10

In what order does paralysis due to non-depolarising NMBs occur?

Answer 10

first: small muscles
- eyes
- facial muscles
larger muscles
- limbs
- pharynx
last: respiratory muscles

Question 11

What are the side effects of non-depolarising NMBs?

Answer 11

• consciousness and pain awareness not affected (must give anaesthesia before paralytic drugs during surgery)
• hypotension because some also block ganglionic nAChRs (newer NMBs are more selective for NMJ)
• tachycardia because some (e.g. pencuronium) can block muscarinic receptors

Question 12

What is the difference in the effect of paralysis that is achieved with non-depolarising and depolarising NMBs?

Answer 12

non-depolarising = flaccid paralysis
depolarising = muscle spasms before paralysis

Question 13

What is an example of a depolarising NMB?

Answer 13

suxamethonium - the only depolarising NMB used clinically

Question 14

What is the structure of suxamethonium?

Answer 14

• 2 ACh molecules linkde together
• acts just like ACh at the receptor
  causes prolonged depolarisation at the motor endplate = loss of excitability

Question 15

Is the effect of depolarising NMBs reversible? If yes, how?

Answer 15

not reversible by AChE

Question 16

In what order does paralysis occur when using a depolarising NMB?

Answer 16

first: larger muscles
- arm, neck, leg muscles
small muscles
- facial and pharyngeal muscles
last: respiratory muscles

Question 17

What are spasmolytics intended to be used for?

Answer 17

• reduce pain due to muscle spasm - not cause paralysis
• reduce spasticity
• retain function

Question 18

What are 4 spasmolytic drugs that work in the CNS?

Answer 18

• diazepam
• baclofen
• tizanidine
• gabapentin

Question 19

What are the two main classes of neurotransmitter in the brain?

Answer 19

glutamate
- excitatory
GABA
- inhibitory

Question 20

What are the subtypes of GABA receptors?

Answer 20

GABAA receptors:
- ionotropic = ion channel
- target for drugs that are sedatives + reduce overactive neurons in the brain (anti-epileptic)
GABAB receptors:
- metabotropic GCPR
- important for nerve transmission in spinal cord
- target to reduce painful muscle spasm

Question 21

What effect does diazepam have? What mechanism?

Answer 21

• sleeping pill

- acts on GABAA receptors

Question 22

What effect does baclofen have? What mechanism?

Answer 22

• used as drug for painful muscle spasms

- acts on GABAB receptors

Question 23

What effect does tizanidine have? What mechanism?

Answer 23

• causes suppression of brain activity

- acts on alpha2 adrenoreceptor on motor neurons

Question 24

What effect does gabapentin have? What mechanism?

Answer 24

• reduction in nerve activity

- acts on voltage dependent calcium channels

Question 25

What are examples of spasmolytic drugs that acts in the periphery (PNS)?

Answer 25

dantrolene

botox - botulinum toxin

Question 26

What are the indications for dantrolene? i.e. when is it used?

Answer 26

• muscle spasticity
• malignant hyperthermia: triggered in some people when under GA = muscle contractions generating heat + lactic acid accumulation

Question 27

What is the mechanism of action for dantrolene?

Answer 27

dantrolene interferes with the release of calcium during skeletal muscle contraction
- affects skeletal muscle more than cardiac and smooth because different calcium channels
= reduces skeletal muscle strength

Question 28

What are the uses for botox?

Answer 28

• cosmetic

- for painful muscle spasm (cervical dystonia - head and neck muscles)

Question 29

What effect does botox have? What adverse effects?

Answer 29

• completely relaxes the local area of muscle for months

- adverse effects = local muscle paralysis

Question 30

What is the mechanism of action for botox?

Answer 30

• SNARE proteins are required for transport of neuromusclar vesicles to the membrane and ACh release into the cleft
• botox cuts the SNARE proteins which prevents ACh release
  = why effect persists for so long as cell must produce new SNARE proteins