Skeletal muscle relaxants

Question 1

A healthy 25-year-old man is undergoing a brief surgical procedurerequiring general anesthesia. He underwent an unremarkable
intubation and induction of anesthesia using IV succinylcholine and inhaled halothane. During the surgery the patient develops muscle rigidity and tachycardia, and his temperature rapidly rises.

What drug should immediately be given to the patient, and what is its mechanism of action?

Answer 1

the patient is experiencing Malignant Hypothermia –> we administer a muscle relaxant –> Dantrolene (Spasmolytic drug)

MoA: Blocks CA+2 channels from the sarcopmalsmic reticulum–> interacts with the RyR1

Question 2

Skeletal muscle contraction is evoked by a
———————— transmission process.

Answer 2

Nicotinic Cholenergic transmission

Question 3

MoA of Skeletal muscle relaxants drugs

Answer 3

1) Neuromuscular blocking drugs–> Act at the skeletal neuromuscular junction (motor end plate) –> may cause paralysis–> used for surgery and assistant ventilation

2) Palsomlytic drugs –> act on CNS –> reduce abnormally elevated tone –> used for neurologic or muscle end plate disease

Question 4

What are the 2 Categories Neuromascualr blocking drugs?

Answer 4

1. Non- depolarizing neuromuscular blocking drugs. (non-depolarizing NMBD)
2. Depolarizing neuromuscular blocking drugs (NMBD)

Question 5

Neuromuscular blocking drugs (Exmaples)

Answer 5

1) Rocuronium, Vecuronium, Atracurium, Tubocuarine (Non-depolarizing NMBD)
2) Succinylcholine (NMBD)

Question 6

MoA of neuromascular blocking drugs

Answer 6

Act at the skeletal neuromuscular junction either:
- pre-synaptically to inhibit ACh synthesis or release
- post-synaptically –> muscle paralysis

Question 7

MoA of non-depolarizing NMBD

Answer 7

(Rocuronium, vecuronium, Atracurium, Tubocurarine)

–> prevent the action of ACh at the skeletal muscle end plate
–> Act at the SNMJ:
- Pre-synaptically to inhibit synthesis or release of ACh.

Question 8

MoA of depolarizing NMBD

Answer 8

Continuous depolarization at the neuromuscular end plate.

• Nicotinic agonist –> depolarizes the Neuromuscular end plate.

Question 9

Administration route of Neuromuscular blocking drugs

Answer 9

IV Administration

Question 10

Indication of Rocuronium, Vecuronium, Atracurium, Tubocuarine

Answer 10

1. surgery.

–> No effect on cardiac,smooth muscles, or
CNS

Question 11

Indication of Succinylcholine

Answer 11

1. surgery.
2. Assisted ventilation

Question 12

PK of Rocuronium, Vecuronium, Atracurium, Tubocuarine

Answer 12

2. Highly polar drugs –> does not cross BBB.
3. metabolized in liver or bile.
4. short durations of action.
5. Tubocurarine –> eliminated by the kidney –> b/c longer action duration.
6. Competitive antagonists –> Reversible and AChE inhibitors.

Question 13

PK of succinylcholine (aka Suxamethonium)

Answer 13

1. Continuous depolarization –> causes muscle relaxation and paralysis.
2. metabolized by cholinesterase in liver and plasma.
3. Short duration of action

Question 14

Adverse effects of Neuromuscular blocking drugs

Answer 14

1. Respiratory paralysis –> Mechanical ventilation required.
2. Tubocurarine (non-depolarizing NMBD)–> Histamine release
3. Succinylcholine –> Muscle pain and damage;
   - Hyperkalemia.
   - Peripheral nerve dysfunction.
   - ­intragastric & intraocular pressure.

Question 15

MoA of spasmolytic Drugs

Answer 15

Act on the CNS –> reduction of excessive skeletal muscle tone without reduction of strength –> reduction of pain and improved mobility

Question 16

Spasmolytic Drugs

Answer 16

1) Baclofen
2) Tizanidine
3) Dantrolene
4) Diazepam
5) Botulinum toixn

Question 17

MoA of Baclofen

Answer 17

Facilitates spinal inhibition of motor neurons.
- GABAb receptor agonist + ↓ release of glutamate.

Question 18

PK of Baclofen + Administration route

Answer 18

• Act in the spinal cord.
  Administration route –> orally/ intrathecal for sever spasticity

Question 19

MoA of Tizanidine

Answer 19

α2 agonist

Question 20

PK of Tizanidine + Administration route

Answer 20

1. Act in the spinal cord.
2. Administered orally for acute and chronic spasms.

Question 21

Indication of Baclofen

Answer 21

sever spasticity

Question 22

Indication of Tizanidine

Answer 22

acute and chronic spasms

Question 23

MoA of Dantrolene

Answer 23

Blocks Ca2+ channels from sarcoplasmic reticulum –> interacts with RyR1

Question 24

Pk of Dantrolene

Answer 24

1. Act in the skeletal muscles –> sensory nerve.
2. Weakens muscle contraction by reducing
   myosin-actin interaction

Question 25

MoA of Diazepam

Answer 25

• BZP
  Facilitated GABA-ergic transmission in CNS –>­
  GABA activation

Question 26

Pk of Diazepam

Answer 26

Act in the spinal cord.

Question 27

MoA of Botulinum toxin

Answer 27

• Acts onn the skeletal muscles motor nerve
• Injected into selected muscles –> reduce pain and severe spasm.

Question 28

administration of Botulinum toxin

Answer 28

IM injection

Question 29

Indication of Botulinum toxin

Answer 29

1. reduce pain and severe spasm.
2. Ophthalmic purposes.

Question 30

Adverse effects of Spasmolytic drugs

Answer 30

1. Sedation;
   Diazepam > baclofen > dantrolene.
2. Tolerance occurs with chronic use

Question 31

AE of Tizanidine

Answer 31

• asthenia.
• drowsiness.
• dry mouth.
• hypotension.
  –> Contraindicated in cardiac patients.

Question 32

AE of Dantrolene

Answer 32

significant muscle weakness.