Neuromuscular Blocking Agents and Drugs for Mysathenia gravis

1. NEUROMUSCULAR BLOCKING AGENT
DRUGS FOR MYASTHENIA GRAVIS
DR. SAROJ K. SUWAL

2. MUSCARINIC AND NICOTINIC RECEPOTRS

3. NEUROMUSCULAR BLOCKING DRUGS
• Drugs that act peripherally on Neuromuscular junction (
Nerve and Skeletal Muscle)
• block impulse transmission between motor nerve
endings and the nicotinic receptors on the
neuromuscular end plate
• act either as
• antagonists (non depolarizing type)
• agonists (depolarizing type) at the receptors

4. CLASSIFICATION OF NM BLOCKERS
• Non depolarizing ( competitive type)→ acts as
antagonist
• Pancuronium, Vecuronium, tubocurarine,Atracurium,
• Depolarizing type (non competitive type)→ act
as agonist
• Succinylcholine(Suxamethonium), Decamethonium

5. NON DEPOLARIZING NM BLOCKERS →
COMPETITIVE TYPE(MOA)→ ACTS AS ANTAGONIST
Relax Muscle
and inhibit muscular contraction.
prevent depolarization of the muscle cell membrane
prevent the binding of acetylcholine
binds to nicotinic receptors
NM Blocking Drugs

6. NON-DEPOLARISING DRUGS
Three types based on their activity:
• Long Acting :
• Pancuronium, Pipecuronium, Gallamine
• Intermediate :
• Vecuronium, Rocuronium,Atracuronium
• short Acting :
• Mivacuronium, Ropcacuronium

7. DEPOLARIZING BLOCKER AGENTS
• Non Competitive
• acts as agonist
• Eg. Succinylcholine (suxamethasone),decamethonium

8. MOA
then paralysis ( Phase II block)– repolarization or
desensitization
first causing muscle contraction (Phase I block)--
depolorizaton
Binds and activate ACh Receptor
Depolarizing agents

9. USES OF NMJ BLOCKERS
• as adjuvant to anesthesia during surgery.
• for skeletal muscle relaxation
• for facilitating endotracheal intubation
• Good intubation conditions – relax jaw, separated vocal chords with immobility, no
diaphragmatic movements
• Treatment of convulsion in psychiatry disorders
• for short procedure eg. diagonostic endoscopy, orthopedic manipulation
• Reversal of competitive neuromuscular blockers

10. DISADVANTAGES:
• Cardiovascular: unpredictable BP, heart rate and arrhythmias
• Fasciculation
• Myalgia
• Increased intraocular pressure
• Increased intracranial pressure
• increased intragastric pressure( cause aspiration)
• Hyperkalemia( fasciculation release k+ into blood)
• Trismus
• Hypotension
• Respiratory Paralysis
• Bronchospasm
• Aspiration of Gastric Contents

11. DIRECTLY ACTING DRUGS - DANTROLENE
• directly act on skeletal muscle as relaxant
• MOA
• no intracellular release of Ca++ from sarcoplasmic reticulum→
prevents depolarization → skeletal muscle relaxation
• Absorbed orally, penetrate brain and produces sedation,
• metabolized in liver, excreted in kidney.

12. USES AND SIDE EFFECTS
• IV used for life saving for Malignant Hypothermia
• Oral Use for → reduce spasm in multiple sclerosis,
cerebral palsy, spinal injuries
• Side effects
• drowsiness, diarrhea, dizziness, headache, fatigue, hepatotoxicity

13. DRUGS FOR MYASTHENIA GRAVIS
Myasthenia gravis
• autoimmune neuromuscular disease
• antibody are produced against NM receptors
of NMJ → decrease number of NM receptor
→ cause Myasthenia gravis
• Marked muscular weakness of skeletal
muscles
• which are responsible for breathing and moving parts of
the body, including the arms and legs

14. MECHANISIM
development of
antibodies directed to
nicotinic receptors
(NR) at the muscle
endplate.
reduction in number of
free NM
cholinoceptors
structural damage to
the NMJ

16. DRUGS AND
THERAPY FOR MG
• Symptomatic therapy
• Neostigmine
• Immuno therapy
• Prednisolone,Azathioprine,
cyclosporine, methothetrate
• RapidTherapy
• Plasma Exchange, IV
immunoglobulin

17. DRUGS
• Neostigmine
• Edrophonium
• MOA
• inhibit the enzyme Acetylcholine esterase which is responsible for degradation of
acetylcholine.
• Hence the concentration of acetylcholine is increased in the Neuromuscular
Junctions.

18. • Corticosteroids : prednisolone
• They inhibit production of nicotinic receptor antibodies -antibodies
• and may increase synthesis of nicotinic receptors.

19. • Thanks