1. NEUROMUSCULAR BLOCKING AGENTS

2. Key Concept
Muscle relaxation does not ensure unconsciousness, amnesia, or analgesia
Neuromuscular blocking agents are used to improve conditions for tracheal intubation, to provide immobility during surgery, and to facilitate mechanical ventilation.
Depolarizing muscle relaxants act as acetylcholine (ACh) receptor agonists, whereas nondepolarizing muscle relaxants function as competitive antagonists.
Depolarizing muscle relaxants are not metabolized by acetylcholinesterase, they diffuse away from the neuromuscular junction and are hydrolyzed in the plasma and liver by another enzyme, pseudocholinesterase (nonspecific cholinesterase, plasma cholinesterase, or butyrylcholinesterase).

3. Key concept. Cont.
With the exception of mivacurium, nondepolarizing agents are not significantly metabolized by either acetylcholinesterase or pseudocholinesterase. Reversal of their blockade depends on redistribution, gradual metabolism, and excretion of the relaxant by the body, or administration of specific reversal agents (eg, cholinesterase inhibitors) that inhibit acetylcholinesterase enzyme activity.
Compared with patients with low enzyme levels or heterozygous atypical enzyme in whom blockade duration is doubled or tripled, patients with homozygous atypical enzyme will have a very long blockade (eg, 4–6 h) following succinylcholine administration.
Succinylcholine is considered contraindicated in the routine management of children and adolescents because of the risk of hyperkalemia, rhabdomyolysis, and cardiac arrest in children with undiagnosed myopathies

4. Key concept. Cont.
Normal muscle releases enough potassium during succinylcholine-induced depolarization to raise serum potassium by 0.5 mEq/L. Although this is usually insignificant in patients with normal baseline potassium levels, a life-threatening potassium elevation is possible in patients with burn injury, massive trauma, neurological disorders, and several other conditions
Doxacurium, pancuronium, vecuronium, and pipecuronium are partially excreted by the kidneys, and their action is prolonged in patients with renal failure.
Atracurium and cisatracurium undergo degradation in plasma at physiological pH and temperature by organ-independent Hofmann elimination. The resulting metabolites (a monoquaternary acrylate and laudanosine) have no intrinsic neuromuscular blocking effects

5. Key concept. Cont.
Hypertension and tachycardia may occur in patients given pancuronium. These cardiovascular effects are caused by the combination of vagal blockade and catecholamine release from adrenergic nerve endings
Long-term administration of vecuronium to patients in intensive care units has resulted in prolonged neuromuscular blockade (up to several days), possibly from accumulation of its active 3-hydroxy metabolite, changing drug clearance, or the development of a polyneuropathy
Rocuronium (0.9–1.2 mg/kg) has an onset of action that approaches succinylcholine (60–90 s), making it a suitable alternative for rapid-sequence inductions, but at the cost of a much longer duration of action.

8. History of neuromuscular blocking agents
Early 1800’s – curare discovered in use by South American Indians as arrow poison
1932 – West employed curare in patients with tetanus and spastic disorders
1942 – curare used for muscular relaxation in general anesthesia
1949 – gallamine discovered as a substitute for curare
1964 – more potent drug pancuronium synthesized

9. Milestones of Neuromuscular Blockade in Anesthesia
1942 introduction of dTc in anesthesia
1949 Succinylcholine, gallamine metocurine introduced
1958 Monitoring of NMF with nerve stimulators
1968 Pancuronium
1971 introduction of TOF
1982 Vecuronium,Pipecurium,atracurium
1992 Mivacurium
1994 Rocuronium
1996 Cisatracurium
2000 Rapacurium introduced and removed

10. Morphological aspects of function

11. Morphological aspects of function
Neuro-muscular junction
Synapses at neuro-muscular junction

12. Depolarizing Blockers

14. Succinylcholine
“Except when used for emergency tracheal intubation or in instances in clinical practice where immediate securing of the airway is necessary, succinylcholine is contraindicated in children and adolescent patients.”

15. Succinylcholine Advantages Disadvantages Rapid onset Hyperkalemia
(burns,massive trauma,denervation.…)
Short Duration
I.M. injection Cardiac Dysrhythmias
Masseter Spasm
Malignant Hyperthermia
Myalgias
Prolonged effect

17. Succinylcholine: Increased intragastric pressure Intraocular pressure
G-E junction opens at pressures > 28cm H20
transient increase up to 40 cm H20
Defasciculate, abolishes the rise
Intraocular pressure
Prevention: defasciculate, benzodiazepam, lidocaine,acetazolamide, deep anesth. at laryngoscopy
Drug of Choice? for the “Glaucoma” and “full stomach”
Recommendations: SUX if possible, priorize, Airway first.
If SUX is used: sedate and defasciculate
transient increase of 8mm Hg ; peaks at 2-4 min
due to contraction of extra-ocular muscles

18. Succinylcholine: Prolonged Apnea after….
Aetiology
1. Disease States
Hepatic Cirrhosis (reduced 50%)
renal disease (50%), returns to normal after renal transplant
malignancy (bronchogenic, GI)
Burns
2. Iatrogenic
echothiopate
anticholinesterases
pancuronium
pheneizine (MAO inhibitor)
glucocorticoids (estrogens)
organophosphates (insecticides)
cytotoxic drugs (cyclophosphamide)

19. Pancronium Bis-quaternary Aminosteroid
High potency therefore slow onset
Long acting
No or slight increase on blood pressure
Vagolytic
Renal clearance

20. Cis-Atracurium one of the stereo isomers of atracurium (15%)
3 X more potent than atracurium
slow onset, intermediate duration
eliminated by Hoffman degradation
Laudanosine as a metabolite
non-organ elimination
doses of 5 X ED95 (0.05mg/kg)
no histamine release
CV stability

22. Reversal of Neuromuscular Blockade
Anticholinesterases:
Edrophonium
Neostigmine
Atropine is added to block the muscarinic effect of the anticholinestrases

23. Anticholinesterases Unwanted side effects Autonomic
Nausea and vomiting
Neostigmine > Edrophonium ?
Edrophonium ( mg/kg) with Atropine ( 7-15 ug/kg)
Neostigmine (40-70 ug/kg) with Glycopyrolate ( mg)

24. Difficulty reversing block
Right dose?
Intensity of block to be reversed?
Choice of relaxant?
Age of patient?
Acid-base and electrolyte status?
Temperature?
Other drugs?

25. Thank you