Neuromuscular Blocker

Question 1

Give example of Non-depolarizing (competitive blockers)

Answer 1

D-Tubocurarine
Cisatracurium
Mivacurium
Pancuronium
Rucuronium
Vecuronium

Question 2

MOA of Non-depolarizing (competitive) blockers

Answer 2

-antagonise the action of Ach in a competitive manner at the postsynaptic nicotinic receptor in NMJ
-result of block: flaccid paralysis

Question 3

Non-depolarizing (competitive) blockers

Answer 3

Sensitivity of muscles to blockade
-face and eye>fingers, limbs, neck, and trunk muscle>intercostal muscle>diaphragm

Muscle recovery is in reverse order

Question 4

Pharmacokinetic of Non-depolarizing blocker

Answer 4

-injection by IV or IM
-highly water soluble
-cannot penetrate membrane
-cannot penetrate BBB
-Metabolised /excreted unchanged in urine.

Atracurium: ester hydrolysis by plasma esterases

Mivacurium: metabolised by plasma pseudocholinesterase

Vecuronium and Recuronium: metabolised by liver

Cisatracurium : Hoffman elimination
Pancuronium : excreted unchanged in urine

Question 5

Clinical use for non-deplorizing blocker (competitive)

Answer 5

Provide muscle relaxation adjunction anesthesia in surgery
-to maintain neuromuscular relaxation throughout the surgical procedure

Cisatracurium can be use for hepatic and renal disease, because of its organ dependent elimination by Hoffman degradation

Question 6

Short-duration and long-duration of depolarizing and Non-depolarizing blocker.

Answer 6

Non depolarizing:
Short duration: mivacurium
Long duration: D-Tubocurarine, Pancuronium, pipercuronium, doxacurium
Intermediate duration: Rocuronium, Vecuronium, Cisatracurium, Atracurium

Depolarizing:
Ultrashort duration: succinylcholine

Question 7

Reversal blocker for Rocuronium & Vecuronium

Answer 7

Sugammadex
-reversal is much faster than reverse with acetylcholinesterase inhibitors
-does not bind with benzylisoquinolones
-excreted unchanged by the kidney
-not metabolize and excretion by the liver

Question 8

Adverse effect of Non-depolarizing blocker

Answer 8

1. Tachycardia : especially Pancuronium because blockade of cardiac M2 cholinoceptors
2. Hypotension: Atracurium & Mivacurium due to histamine release
3. Urticaria
4. Bronchospasm

Question 9

MOA of succinylcholine (depolarizing blocker)

Succinylcholine
-injected Iv
-rapid onset
-short duration

Answer 9

-bind to nicotinic receptor to open channel and cause initial depolarization of motor end plates and transient contraction of muscle motor subunit (muscle fasciculation)

-cannot be reverse by acetylcholinesterase activity, so prolonged activation of nicotinic receptor. (phase I)

-later in phase II, the blockade become identical to Non-depolarizing, possible to reverse by acetylcholinesterase inhibitors
-results in flaccid paralysis.

Question 10

Clinical uses of succinylcholine

Answer 10

-to facilitates endotracheal intubation and endoscopy examination once general anesthesia is induced.

-adjuvant to relax muscle in a short surgery

Question 11

Adverse effect of succinylcholine

Answer 11

1. Prolonged apnea
2. Hyperkalemia: persistent depolarization lead to efflux of potassium
3. Postoperative muscle pain (myalgia) : muscle fasciculation
4. Bradycardia, cardiac arrest, ventricular dysrhythmias
5. Increase intraocular pressure

Question 12

Treatment of malignant hyperthermia (rise in body temperature)
-heat production in skeletal muscle & excessive release of calcium from sarcoplasmic reticulum

Answer 12

Dantrolene
-a muscle relaxant drug that bind RyR1 receptor and blockers these calcium release channel on sarcoplasmic reticulum.