ADVANCED PHARMACOLOGY - 1

TOPIC - NEUROMASCULAR BLOCKERS & LOCAL

ANESTHETICS
PRITHWIRAJ JANA
ACP25PHCL003

[Link]-1st Sem/1st Year

Department Of PHARMACOLOGY
Acharya and B M Reddy College of Pharmacy
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 NEUROMASCULAR
BLOCKERS
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• Introduction
• Whenever a nerve joins a muscle, there is no anatomical continuity
between them.
• There is a small gap between a nerve and a muscle. It is called as Synaptic
Cleft.
• A neuromascular junction consist of presynaptic cleft,synaptic Cleft and
postsynaptic cleft
• These drugs act at NMJ.
• At NMJ, ACh works as a neurotransmitter through nicotinic receptors.
• Hence, drugs blocking nicotinic actions of ACh perform as neuromuscular
blocking agents.
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 DEFINITION :

• Neuromuscular blockers are drugs that produce skeletal muscle

relaxation by blocking transmission of nerve impulses at the
neuromuscular junction, without causing loss of consciousness or pain
relief
• They paralyze skeletal muscles by preventing acetylcholine from
producing muscle contraction.

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 Classification
 Non-depolarising blockers (competitive blockers):
 Long-Acting
 Metocurine, Doxacurium, Pancuronium, Pipecuronium, D - Turbocurarine
 Short-Acting
 Atracurium, Cis-atracurium, Mivacurium, Vecuronium, Rocuronium.
 Depolarising blockers (persistent depolarisers) :
 Decamethonium, Succinyl Choline.

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Non-depolarising blockers (competitive blockers):
 Mechanism Of Action:

Drug

bind with nicotinic Receptor

Prevent binding of acetyle choline to nicotinic receptor

Thus blockade the action of Acetylecholine by competitive blocakade

As it compete with acetylecholine to bind nictonic receptor it also called

competitive blockers

Inhibit Na+ channel opening

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 Inhibit Na+ influx in the cell

Inhibit Depolarisation

Inhibit generation of Action Potential

Paralysis

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 Pharmacological Action :
 Musculoskeletal System (Target Organ):
• NMBAs cause skeletal muscle paralysis, starting with small, rapid-moving
muscles (eyes, face) and progressing to large muscles and the diaphragm
 Histamine Release:
• Directly act on mast cell & produce Histamine causes Brochospasm.
• Increase salivary secretion
 Vagolytic (Antimuscarinic) Effects:
• Pancuronium inhibits M2 muscarinic receptors in the heart, resulting in
increased heart rate and blood pressure

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 Respiratory System:
• They cause direct paralysis of respiratory muscles, including the
diaphragm, requiring mechanical ventilation
 Eye Muscles:
• Early paralysis of extra-ocular muscles
• Useful in ophthalmic surgeries
 Autonomic ganglia:
• Partially blockade both autonomic ganglia & adrenal medulla
resulting fall of B.P.
 CNS:
• Does not cross BBB & PB i.e no significant effect on CNS
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• Pharmacokinetics:
• These drugs are not absorbed when given orally. They are given
intravenously
• They have relatively small volume of distribution (Vd). None of them cross
blood-brain barrier, placental barrier
• Metabolism of drugs depend on drugs metabolism by liver- Vecuronium,
Rocuronium,Pancuronium
• metabolise by plasma (Hofmann elimination) - Atracurium,Cisatracurium
• Eliminate by both bile and renal route

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 Therapeutic use :
• Adjuvant to anesthetics to produce muscle relaxation for
surgery.
• In orthopedic fracture or correction for relocations of
bones.
• Spastic neurological condition.
 Adverse Reaction::
• Hypoxia and respiratory paralysis may be caused by d-TC like drugs.
• Bronchospasm,
• Hypo-tension and
• Bradycardia.
• Pancuronium may cause tachycardia.

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Depolarising blockers:
Mechanism of Action :
Succinylcholine has similar structure as ACH
and bind to nicotinic receptor

Act like ACH and open Na+ channel

Cause Depolarisation

Succinylcholine does not rapidly broken by

acetyle choline esterase

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 Persistent depolarisation

Initial muscle fasciculations

Inability of muscle to repolarise

After long time the drug get broken by Ache enzyme

and repolarisation take place

Due to prolong depolarisation the receptor

get desensitation
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 Thus, even through the membrane repolarise but the receptor does not
respond to Acetyle choline,

which lead to paralysia

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 Pharmacological Actions
 Skeletal muscle :
• Initial transient muscular fasciculations & - twitching, mostly · in chest &
stomach regions,
• followed by skeletal muscle paralysis.
 CVS:
• Initially hypotension and bradycardia may result from stimulation of vagal
ganglia.
• This is followed by hypertension and tachycardia due to stimulation of
sympathetic ganglia.
• Higher doses can cause cardiac arrhythmias.

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Pharmacokinetics
• It is not absorbed orally and does not cross blood brain barrier or
placental barrier.
• Administered through i.v. route
• Its metabolise by pseudocholinestearse enzyme in plasma
• Excrete through renal route.

 Adverse Reaction:
• Postoperative muscle pain:
• Hyperkalemia:
• Cardiac arrhythmias:
• Malignant hyperthermia

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 LOCAL
ANESTHETICS

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 DEFINITION:

• Local anesthetics are drugs that cause a temporary, reversible loss of

sensation—specifically pain—in a confined area of the body without
producing loss of consciousness
• These agents can be applied topically to the skin/mucous membranes,
injected locally for infiltration, or used as nerve blocks (including spinal or
epidural anesthesia).
• The effect is typically immediate to fast-acting, lasting from 30 minutes to
several hours.

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 LOCAL ANESTHETICS:
 According To Clinical Use :
 Injectable Anesthetics:
• Low potency, short duration: Procaine, Chloroprocaine duration
• Intermediate potency and duration: Lidocaine (Lignocaine ), Prilocaine
• High potency, Long durationg: Tetracaine, Bupivacaine, Ropivacaine,
Dibucaine
 Surface anaesthetic:
• Soluble : Cocaine, lignocaine, Tetracaine
• Insoluble : benzocaine, Butylaminobenzoate

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 Based on Chemical Structure:

• Esters : Cocaine, procaine, benzocaine, tetracaine

• Amide : Lignocaine, Bupivacaine, Dibucaine, prilocaine, Ropivacaine

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 MECHANISM OF ACTION:
• The primary mechanism is blockade of voltage-gated sodium channel,
• LA diffuses through cell membrane and bind to voltage-sensitive sodium
channels
• No entry of Na+ ions into the cells
• Inhibit depolarization
• Inhibit generation of action potential
• Inhibit generation and conduction of action Potential to CNS
• Local Anesthesia

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 PHARMACOLOGICAL ACTION:
 On CNS:
• Initially causes CNS stimulation and in higher doses it causes depression. They
causes excitement, tremors, twitching, restlessness and convulsions.
 On Heart:
• Decreases abnormal pacemaker activity, contractility, conductivity, excitability,
heart rate,
• cardiac output and increases refractory period.
 On Blood vessels:
• They produce hypo tension due to sympathetic blockade,
• They also cause Arterioral Dilation.

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 Smooth muscle:
• LAs depress contractions in the intact bowel.
• They also relax vascular and bronchial smooth muscles.
 Local actions:
• On local administration, LAs bring about reversible loss of sensation as
already discussed

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 Pharmacokinetics
• It can be applies topically on skin or directly injectin to the tissue
• ester type drug undergoes metabolism in plasma by
pseudocholinesterase.
• Amide type drug undergoes metabolism in liver by CYP450 enzyme
• Excrete through kidney

 Therapeutic use :
• Nerve block – regional anaesthesia for limb and nerve surgeries
• Spinal & epidural anaesthesia – lower abdominal, pelvic, and lower limb
surgeries; labour pain
• Cardiac use (lidocaine) – treatment of ventricular arrhythmias.
• Infiltration anaesthesia – minor surgical and dental procedures.
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 ADVERSE EFFECTS
• On CNS:
Headache, excitement, tremors, twitching, restlessness and convulsions.
• On CVS
Bradycardia, hypotension, cardiac arrhythmias and rarely cardiovascular collapse
and death.
• Hypersensitivity reactions:
Skin rashes, itching, erythema, urticaria, wheezing, bronchospasm and rarely
anaphylactic reaction.

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 THANK YOU
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