A.15

Question 1

centrally and peripherally acting skeletal muscle relaxants

Answer 1

1. euromuscular blocking agents (act locally, at the NMJ):
   -Non-depolarizing: (cis)atracurium, mivacuriun, pipecuronium, rocuronium
   -Depolarizing: Succynylcholine
2. Spasmolytic agents (act centrally, at the level of CNS):
   Diazapem, Tolperisone, Baclofen, Tizanidine
3. Direct acting muscle relaxants:
   Dantrolene, Botulinum toxin

Question 2

Baclofen

Answer 2

MOA: GABAB receptor agonist;
ROA: p.o, infusion, injection;
Effect: Gi →K+-efflux → Hyperpolarization→ long lasting muscle relaxant effect;
IND: relieve muscle spasticity (cerebral palsy, MS, stroke);
SEs: sedation, weakness, rebound spasticity upon abrupt withdrawal

Question 3

Tolperisone

Answer 3

MOA: unknown mechanism;
ROA: p.o;
Effect: reduction of muscle reflex;
IND: acute spasm due to injury;
SEs: sedation, confusion, strong anti-muscarinic effect

Question 4

Diazepam

Answer 4

MOA: GABAA receptor agonist;
ROA: p.o, i.v;
Effect: Cl–influx→hyperpolarization→muscle relaxant effect;
IND: chronic spasm due to cerebral palsy, stroke, SC injury, Acute spasm due to muscle injury, Panic disorders, anxiety disorder, PTSD;
SEs: CNS depressant, tolerance;
Extra: long actine metabolite, hepatic metabolism; DOA: long acting ~60h, with metabolite ~150h;
Dosage: 5-10mg p.o, for status epilepticus-i.v.30mg

Question 5

Tizanidine

Answer 5

MOA: α2-agonist;
ROA: p.o;
Effect: pre-synaptic stimulation→inhibition of Glut. release→ muscle relaxation;
IND: Relief of cerebral or spinal muscle spasms, cramps (cervial+lumbar syndromes);
SEs: Weakness, sedation, hypotension;
Extra: Renal&hepatic elimination

Question 6

Dantrolene

Answer 6

MOA: Ryanodine receptor (RyR) antagonist;
Effect: Inhibits Ca2+ release in ER in the sk. muscle→↓actin-myosin interaction;
IND: Malignant hyperthermia
SEs: hepatotoxicity, muscle weakness;
Contra-IND: people with liver diseases;
ROA: p.o,i.v

Question 7

Botulinum toxin

Answer 7

MOA: Inhibit SNARE proteins fusion;
ROA: direct injection to muscle;
DOA: up to 2-3 months Effect: prevents synaptic exocytosis of ACh from terminals of motor axons→ Flaccid paralysis;
IND: Spasm due to cerebral palsy, MS, Cervical dystonia, locally in botox;
contra-indication: Neuromuscular disease (e.g MG)

Question 8

(cis)atracurium, Mivacurium, Pipecuronium, Rocuronium

Answer 8

MOA: competitive antagonist of NM ACh-R;
ROA: i.v.;
Effect: bind to R instead of ACh→no opening of ion channel→muscle paralysis;
IND: surgical narcosis, artificially respired patients, intubation, tetanus, epileptic seizure;
SEs: Histamine release (itchiness, bronchospasm, hypotension), Muscle weakness (prolonged apnoea)

Question 9

(cis)atracurium

Answer 9

DOA: cisatra- 20-30min, atra- 15-35min;
Extra: Spontaneous metabolism (Hoffmann-elimination), izoquinoline structure

Question 10

Mivacurium

Answer 10

DOA: short acting (10-15min);
Extra: Metabolized by pseudocholinesterase, izoquinoline structutre

Question 11

Pipecuronium

Answer 11

DOA: long acting (60-90min);
Extra: filtration by the kidney,steroid structure

Question 12

Rocuronium

Answer 12

Extra: hepatic metabolism;
DOA: dose dependent- 15-110min

Question 13

Succynylcholine (suxamethonium)

Answer 13

MOA: selective agonist NM receptor (depolarizing); ROA: i.v.; Effect: sk. muscle relaxant, provides depolarizing blokade that cannot be antagonized by AChE inhibitors;
IND: surgical procedures where rapid onset +brief duration is needed (e.g. intubation, bronchoscopy); DOA: short acting (5-10min);
SEs: muscle pain, arrhythmia (bradycardia), hyperkalemia, vomiting, malignant hyperthermia; Extra: rapid metabolism by pseudocholinesterase