Skeletal Muscles

Question 1

Drugs causing contraction

Answer 1

1. Tetanus toxin - strong spastic contraction
2. Halothan, succinylcholine, antipsychotics - activators of the mutated ryanodine receptors
3. Sympathomimetics - increase muscle strength
4. Centrally acting - any convulsive agent

Question 2

Muscle relaxants

Answer 2

1. Centrally acting
   - spasmolytics
2. Peripherally acting
   - block the nmj - paralysis
   - botulinum toxin
   - tetracycline, aminoglycosides

Question 3

Centrally acting muscle relaxants

Answer 3

Baclofen 
Mephenesine
Guaiphenesine 
Chlorzoxasone
Diazepam/benzodiazepines 
Tiazanidine
Tolperisone
Carisoprodol

Question 4

Drugs for spasticity

Answer 4

Baclofen

• GABAb agonist (inhibitory neurotransmitter)
• highly sedative
• only for chronic events, e.g., ms
• rapidly absorbed after oral administration
• excreted by kidneys
• half-life: 2-4 h

Question 5

Drugs for acute muscle spasm

Answer 5

Due to overdose, trauma, disc herniation, ostheoarthritis

1. Mephenesine - parenteral
2. Guaiphenesine - parenteral
3. Chlorzoxasone - enteral

Question 6

Drugs for acute spasticity

Answer 6

1. Diazepam and benzodiazepines potentiate GABAa
   - used for locked mouth
2. Tizanidine - a2 agonist - sedative
3. Tolperisone - not sedative, unknown mechanism
4. Carisoprodol - abuse potential, hepatotoxic

Question 7

Possibilities to relax skeletal muscles

Answer 7

1. Spasmolytics - centrally acting
   - decrease tone of the skeletal muscle
2. Peripheral muscle relaxant
   - paralyze the muscle (total relaxation)
   - presynaptic drug:
   — botulinum toxin, omega-conotoxin (full relaxation)
   — aminoglycosides, tetracycline (weakness)
   - postsynaptic drug:
   —curare derivatives - complete block
   — depolarize got muscle relaxants - agonist of Nm
   — ryanodine antagonists - special indication

Question 8

Indication of peripheral muscle relaxants

Answer 8

• muscular relaxation during surgery
• relax muscles of artificially respired patients
• electroshock
• intubation
• tetanus
• epileptic seizure not relieved by antieleptic
• intoxication with certain medicine, eg; theophylline, amphetamine

Question 9

Classification of curare

Answer 9

1. Izoquinolones - curium
   - d-tubicurarine (not used)
   - doxacurium
   - atracurium
   - cisatracurium
   - mivacurium
2. Steroids - curonium
   - pancuronium
   - pipecuronium
   - vercuronium
   - rocuronium

Question 10

Time order of curare paralysis

Answer 10

Full paralysis 2-6 min

• outer eye muscles
• facial muscles
• pharyngeal muscles
• extremities
• truncal muscles
• respiratory muscles

Question 11

Curare type muscle relaxants

Answer 11

Competitive antagonist to Nm ACh receptor in NMJ

4amine, no CNS effect

Iv administration

Selective

Question 12

Long lasting curare

Answer 12

60-180 min

• doxacurium
• pancuronium
• pipecuronium

Question 13

Intermediate acting curare

Answer 13

20-40 min

Vercuronium
Rocuronium
Atracurium
Cisatracurium

Question 14

Short acting curare

Answer 14

10-15 min

Mivacurium

Question 15

Adverse effect of curare

Answer 15

Recurarization - after suspending the effects reappearing muscle weakness

Ganglion blockade - pancuronium: HT, tachycardia

Histamine release - mivacurium, atracurium: itching, brinchospasm, hypotension

M2 block - pancuronium: tachycardia

Ne release and reuptake inhibition - pancuronium: tachycardia

Metabolite of atracurium - laudanosin: muscle spasm, convulsions

Question 16

Suspending/terminating the curare effects

Answer 16

AChE INHIBITORS: neostigmine, distigmine - coadministered with atropine in order to antagonize their parasympathomimetic effects

SUGAMMADEX: neutralize the steroid structure in the plasma

Question 17

Factors influencing the curare effects

Answer 17

1. Enhancing
   - general anesthesia
   - aminoglycosides and tetracycline
   - local anesthesia
   - myasthenia gravis
2. Decreasing
   - AChE inhibitors - peripheral motor neuron
   - motor neuron lesion

Question 18

Depolarizing muscle relaxants

Answer 18

Succinylcholine

Question 19

Succinylcholine/suxamethonium

Answer 19

• depolarizing muscle relaxants
• divides depolarizing blockade that cannot be antagonized by AChE inhibitors
• no antidote- need to restore the membrane potential in the muscle (done by muscle)
• duration after iv: 5-10 min
• order of paralysis; arms-neck-legs-respiratory muscles-facial muscles-pharyngeal muscles
• metabolism: pseudo cholinesterase In the blood to the liver

Indication: short surgeries, intubation, electroshock, short diagnostic procedures (bronchoscope)

Question 20

Development of depolarizing blockade

Answer 20

Succinylcholine is a selective agonist of the Nm receptor and AChE does not metabolize it.

Due to the longer stimulus of the receptor, Sodium influx is higher resulting in depolarization of the surrounding membrane.

In this are, the VGSC cannot return to their resting closed state. Instead they remain the the inactive state causing AP generation to stop and the muscle is paralyzed.

This can not be antagonized by AChE in the beginning.

Question 21

Adverse effects of succinylcholine

Answer 21

Muscle pain 
Arrhythmia 
Bradycardia
Hyperkalemia 
Vomiting 
Higher intraocular pressure 
MALIGNANT HYPERTHERMIA 

REASONS FOR Malignant hyperthermia

• genetic disorder affecting ryanodine receptors
• idosynchrasia
• shivering - heat production
• lactacidosis
• myoglobinemia/Uria
• acute renal failure

Treatment of malignant hyperthermia

• danteolone - hepatotoxic
• bicarbonate infusion to acidosis
• physical cooling of patient