Neuromuscular blocking agents in large animals

Neuromuscular Blocking Agents

Submitted by – Amandeep

Department Of Veterinary Medicine

L2013V40M

INTRODUCTION

• Agents that interfere with transmission of

nerve impulse from somatic nerve ending to

skeletal muscle fibres

• Profound muscle relaxation & even paralysis

of skeletal muscles

Muscle Relaxants

Peripheral acting muscle

relaxant

Centrally acting muscle relaxant

Peripheral Acting Muscle Relaxant

Neuromuscular blocking agents

Directly acting drugs

Why?

• Inhalant anesthetics(IA) are complete anesthetics

• Fulfill triad-unconsciousness, analgesia & muscle

relaxation- of anesthesia

• Light planes- good loss of consciousness

• Deeper planes- analgesia & M. relaxation

• Cardiovascular compromise

Balanced Anesthesia

• Low concentration of IA to provide unconsciousness

• Analgesic to inhibit nociceptive processing

• NMBA to relax skeletal muscle

Physiology

At Microscopic Level

• Protruded circular area- binding site for Ach

• Pit- extracellular opening for ion channel

• Ach binds to one R• R composed of alpha,

beta, gamma & delta• 2 molecules of Ach bind

to 2 alpha subunits• Protein rotates into new

conformation

Mechanism Of Action

Other Mechanisms

• Densensitized state

• Channel blockade

Uses of NMBA

• Adequate surgical muscle relaxation without compromising

recovery

Absolute relaxation, eg : intra-ocular procedures, microsurgery

Specific muscle relaxation, eg : laparotomy , Caesarean

section, some orthopaedic surgery (reduction of dislocations),

diaphragm surgery

Uses of NMBA

• Reduction of anaesthetic dose

• Preservation of cardiopulmonary function

• Reduced operating times in 'high risk' patients

• Where positive pressure ventilation (PPV) required

• Where spinal reflexes need to be suppressed, eg: ear canal

surgery

Non – Depolarizing Depolarizing

• Act by competitively

blocking the binding of ACh

to its receptors / directly

block the ionotropic activity

of the ACh receptors

• Bind to Ach receptors but no

activation occurs

• Act by depolarizing the

plasma membrane of the

skeletal muscle fibre similar

to Ach

• Bind to Ach receptors

causing activation

Muscle paralysis

Neuromuscular Blocking Agents

• Non depolarising-

1. Long acting e.g tubocurarine

2. Intermediate acting e.g vecuronium, atracurium

3. Short acting e.g mivacurium

• Depolarising eg suxamethonium & decamethonium

Dose rates

• Pancuronium –

• In cattle - 0.04mg/kg, slow I/V(initial dose),

followed by increments of 0.008mg/kg

• In horse – 0.06mg/kg, , slow I/V(initial dose),

followed by increments of 0.001mg/kg

Dose rates

Doxacurium- usually not used

Atracurium –

Horse@ 0.15mg/kg, slow I/V(initial dose), then

increments of 0.06 mg/kg

Vecuronium- Horses@ 0.1 mg/kg slow I/V initial dose,

then increment of 0.02mg/kg

Mivacurium- it does not need reversal

Drug ( Depolarizing NMB)

Horse(mg/kg)

Cattle(mg/kg)

Succinyl choline(Scoline ®)

0.12-0.15 0.01-0.02

Non Neuromuscular effect

• Cardiovascular effect

• Histamine release

• Placental transfer

• CNS effects

• Protein binding

Non Neuromuscular Effect Of Succinylcholine

• Hyperkalemia

• Intraocular pressure

• Intragastric pressure

• Intracranial pressure

• Muscle soreness

Reversal Of NM Blockade 

Achieved by establishing high concentration of acetylcholine at the

binding site

Atropine (0.04 mg/kg S/C)

Glycopyrrolate (0.01 mg/kg I/M) administered intravenously atleast

one minute prior to the administration of reversal agent to block the

muscarinic effects of acetylcholine

Reversal Of NM Blockade

• Neostigmine 0.1 mg/kg I.V

• Edrophonium 1.0 mg/kg I.V

Cholinesterase Reversal

Cholinesterase reversal by increasing ACh and

displacing NMBA from receptors

Sugammadex MOA

• Modified cyclodextrin

• Cavity created by ring

is lipophilic, exterior is

hydrophilic

• Encapsulate lipophilic

drugs yet remain soluble

in water

Sugammadex MOA

• Resultant sugammadex bound NMBA (inclusion

complex) is then excreted by the kidneys

• Renal clearance of the NMBA has been found to be

enhanced by sugammadex encapsulation

Thanks