In this presentation I tried to explain the classification of muscle relaxants. along with differences between these classes. there is also a brief discussion about NMT and how they work. furthermore it has dose, maintenance dose, adverse effects and how to manage toxicity about these drugs.

1. NEUROMUSCULAR
BLOCKING AGENT
DR SARDAR SAUD ABBAS
PG-III, KTH, MTI

2. CONTENTS
 NEUROMUSCULAR TRANSMISSION
 CLASSIFICATION OF MUSCLE RELAXANT
 MECHANISM OF ACTION OF MUSCLE RELAXANT
 REVERSAL OF NEUROMUSCULAR BLOCKAGE
 RESPONSE TO PERIPHERAL NERVE STIMULATION
 DEPOLARISING MUSCLE RELAXANT
 NON DEPOLARISING MUSCLE RELAXANT
 DIFFERENCE B/W DEPOLARISING AND NDMR

3. HOW DOES NM TRANSMISSION
OCCURS
 Neuromuscular junction consist of nerve end, synaptic cleft and muscle
endplate
 Neurotransmitter at this junction is acetylcholine
 Synthesized in the nerve cytoplasm
 Choline enters the nerve end which regulated by Na+ and K+ pump
 Acetyl coA is synthesized in mitochondria
 Acetyl coA + Choline  acetylcholine
 Enzyme responsible is choline acetyltransferase
 Calcium enters nerve end and ACH is released in synaptic cleft from
vessicle

5. ACETYLCHOLINE RECEPTOR
STRUCTURE
Receptor contains five protein:
 Two Alpha subunits
 Single Beta
 Single Delta
 Single Epsilon
1. Acetylcholine only binds to two alpha submit
2. The channel with not open if only one is occupied
3. Extra juncntional receptor is present in fetal and immature
4. This sub unit is of gamma protein
5. Each neuromuscular junction contain 50 lakh (5 million) receptor's
6. Only 5 lakh (0.5 million) is required for normal muscle contraction

7. WHAT IS EATON LAMBERT
MYSTHENIC SYNDROM?

8. WHAT IS MYASTHENIA
GRAVIS?

9. EATON LAMBERT MYSTHENIC SYNDROME:
 Decrease release of Ach
MYASTHENIA GRAVIS:
 Decrease number of receptors

10. CLASSIFICATION BASED ON
CHEMICAL STRUCTURE

11. CLASSIFICATION BASE ON
DURATION OF ACTION

12. SEQUENCE OF MUSCLE BLOACKADE
 Laryngeal muscles and diaphragm may require double dose required to
block adductor pollicis
 Diaphragm is considered as most resistant muscle
 Muscle of fasiculatiom after sux are first seen in eyelid, jaw, pharyngx,
larynx, muscle of respiration, abdomen and trunks muscles then
peripheral muscles.
 The sequence of recovery is also same
 First to recover are central muscles (laryngeal, pharyngeal, respiratory
and trunk)

13. SUXAMETHONIUM (SUCCINYLCHOLINE)
 Depolarizing muscle relaxant
 Should be store at 4 degree
 Onset of action: 30-60 sec
 Duration of action: <10 mins
 Dose: 1-2mg/kg
 Depolarizing muscle relaxant act as ACH receptor agonist
 Two acetylcholine molecules makes one succinylcholine
 Succinylcholine attach on ACH receptor and causes muscle action
potential

14.  Short duration is due to small volume distribution and very low lipid solubility
 It is rapid metabolized by pseudocholinesterase
 Single dose sux casuses Phase I block and if repeated within 8 mins it cause
phase II ( prolonged block
Duration of action of Sux is prolonged by :
 High doses
 Infusion of sux
 Hypothermia
 Reduced levels of pseuodocholinesterase
 Pregnancy
 Liver disease

15. What is Dibucaine?
What us Dibucaine Number?
What sort of genetic condition prolongs
sux duration of action?

16.  Dibucaine, a local anesthetic , inhibits normal pseudocholinesterase enzyme
activity by 80%
 The percentage of inhibition of pseudocholinesterase activity is termed the
dibucaine number
 Homozygous atypical enzyme condition causes 4-5 hr bloackage after sux
administration
 Prolonged paralysis from sux is treated with mechanical vent and sedation until
muscle function return

17.  Sux cannot be reversed by neostigmine
It might prolong the block by two mechanism:
1. By inhibiting acetylcholinesterase, higher Ach conc. Which intensifies
depolarization
2. It also reduce hydrolysis of sux by inhibiting pseudocholinesterase.
SYSTEMIC EFFECT
CVS:
1. Low doses Sux cause bradycardia
2. But higher dose usually has positive inotropic and chronotropic effect,
evevating catecholamine
3. Children has profound bradycardia
Skeletal Muscle:
1. Causes faciculations
2. Myalgia is are common. Can be reduced by giving (0.06-0.1) Rocuronium

18. Electrolye:
 Administeration of Sux increase 0.5 mEq/l postassium.
 Hyperkalemic cardiac arrest can be correct with calcium, insulin, glucose,
bicarbonate.
Hyperkalemia usually seems to peak 7-10 days after burn injury
But can be given with in 2 days of burn injury

19. Intragastric pressure:
 Fasiculation increase intragastric pressure, which offsets by an increase in
lower esophageal sphincter tone.
1. Can cause masseter muscle rigidity
2. But its transient
3. Prolong masseter muscle rigidity is suggestive of malignant hyperthermia.
4. Can trigger malignant hyperthermia after administration
Intracranial Pressure:
Slightly increase cerebral blood flow
Which increases intracranial pressure
This can be decreases by hyperventilation

20. NON DEPOLARIZING MUSCLE
RELAXANT
Mechanism of action:
 NDMR are competitive antagonist of Ach receptors
 They bind to the same alpha subunit
 It binds to the receptor and prevent depolarization

23. Quick NDMR POINTS
 Shortest acting: Gantacurium
 Longest acting: Doxacurium
 Cardiostable: Vecuronium
 Cardio unstable: Pancuronium
 Contra indicated in Kidney disease: Vecuronium and Doxacurium
 Doesn’t cross blood brain barrier: Gallamine

24. FACTOS PROLONGING
NEUROMUSCULAR BLOCKADE
1. Neonates
2. Old age
3. Obesity
4. Hepatic disease
5. Renal disease
6. Inhalation agent
7. Local anesthetic (except procaine)
8. Hypothermia
9. Hypocalcemia
10. Hypokalemia

25. RESPONSE TO PERIPHERAL NERVE STIMULATION
DEPOLARISING MUSCLE RELAXANT
Train of 4:
 4 twitches
 In 2 secs
 2 Hz frequency
 Each of 2ms long
Tetany:
 Sustained stimulus
 Of 50-100
 Lasting 5sec

26. Double Burst Stimulation (DBS):
 Three short
 High frequency stimulation
 Seperated by 20-ms (50 Hz)
 Followed by 750ms later by two or three
 (DBS 3,2) (DBS 3,3)

28. SIGNS OF ADEQUATE REVERSAL

29. COMMON CAUSE OF INADQUATE
REVERSAL

30. DIFFERENCE B/W DEPOLARISING
AND NDMR

31. THANK YOU