Neuro muscular blockers

Neuromuscular Blockers

• Competitive Antagonists of the Nicotinic Receptor

e.g. curare (d-tubocurarine), vecuronium, pancuronium, atracurium, etc…

• Depolarizing Blockers

e.g. succinylcholine, decamethonium

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D-tubocurarine pancuronium

Vecuronium

Decamethonium

SuccinylcholineDepolarizing

Blockers

CompetitiveBlockers

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Neuromuscular blockers differ from each other in:

• Mechanism of action

• Duration of action

• Speed of onset and offset of action

• Selectivity of action and safety margin

• Adverse effects

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Agent Pharmacological

Properties

Onset time (min)

Duration

(min)

Elimination

Succinylcholine Ultrashort acting;

Depolarizing1-1.5 6-8

Plasma cholinesterase

D-tubocurarine Long duration;

Competitive4-6 80-120

Renal and liver

Atracurium Intermediate duration;

Competitive2-4 30-40

Plasma cholinesterase

Mivacurium Short duration;

Competitive2-4 12-18

Plasma cholinesterase

Pancuronium Long duration;

Competitive4-6 4-6

Renal and liver

Rocuronium Intermediate duration;

competitive1-2 1-2

Renal and liver

Classification of Blockers

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Muscle AP

Nerve AP

Left Leg Muscle Stimulation

Right Leg Nerve Stimulation

Right Leg Muscle Stimulation

Site of Action of d-Tubocurarine

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G: gallamine; TC: tubocurarine; NEO: neostigmine; S: succinylcholine.

Non-depolarizing Block

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Depolarizing Block

C10: decamethoniumTC: tubocurarineNEO: neostigmineS: succinylcholine

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Competitive Depolarizing

Effect of previous d-tubocurarine

Additive Antagonistic

Effect of previous decamethonium

None/antagonistic May be additive

Efect of cholinesterase inhibitors

Reverse No antagonism

Effect on motor end plate

Elevated threshold to Ach; no depolarization

Partial, persisting depolarization

Initial excitatory effect None Transient fasciculations

Effect of KCl or tetatnus on block

Transient reversal

No antagonism

Comparison of Competitive and Depolarizing Blocking Agents

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Dual Block by Depolarizing Agents

C10: decamethonium; NEO: neostigmine; TC: tubocurarine

NEO reversedthe blockadeby C10.

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Depolarizing Blocker

Competitive Blockade

Competitive Blocker

Noncompetitive Blockade

(desensitization)(electrogenic Na pump)

(direct channel block)

Changing Nature of Neuromuscular Blockade

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Sequence of Paralysis

Fingers, orbit (small muscles)

limbs Trunk neck

IntercostalsDiaphragm

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Other Effects of Neuromuscular Blockers

• Action at Autonomic Ganglia e.g. d-tubocurarine blocks, succinylcholine may stimulatenewer agents have less ganglionic effects

• Histamine Release e.g. d-tubocurarinebronchospasm, bronchial and salivary secretions

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Adverse Effects/Toxicity• Hypotension• Decreased tone and motility in GI tract• Depolarizing agents can cause increased K

efflux in patients with burns, trauma, or denervation and lead to hyperkalemia

• Prolonged apnea (many reasons, check for pseudochlinesterase genetic polymorphism)

• Malignant hyperthermia (succinylcholine + halothane especially)

• Sinus bradycardia/junctional rhythm (with succinylcholine)

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Systolic BP Systolic BP

% Change in Systolic BP with d-Tubocurarine as a Function of Dose and Depth of Anesthesia

Increasing Doseof d-tubocurarine

Increasing Depth(% Halothane)

0.25%

0.5%

0.75%

6 mg/m2

12 mg/m2

18 mg/m2

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Influence of Type of Anesthetic on Enhancement of Neuromuscular Blockade By d-Tubocurarine

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HR CO

SVR MAP

Hemodynamic Effects of d-Tubocurarine and Pancuronium

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Drug Interactions

• Cholinesterase Inhibitors (antagonize competitive and enhance depolarizing)

• Inhalational Anesthetics (synergistic)

• Aminoglycoside Antibiotics (synergistic)

• Calcium Channel Blockers (synergistic)

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Therapeutic Uses

• Adjuvant in surgical anesthesia

• Orthopedic procedures for alignment of fractures

• To facilitate intubations – use one with a short duration of action

• In electroshock treatment of psychiatric disorders

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