Depolarising and non

depolarising SMRM. Aravind

MBBS II yr.

NEUROMUSCULAR

BLOCKERS DEPOLARISING BLOCKERS:

Succinyl choline, decamethonium

NON DEPOLARIZING BLOCKERS:

d- Tubocurarine

Pancuronium

Doxacurium

Pipercuronium

Vecuronium

Atracurium

cisatracurium

Rocuronium

Rapacuronium

Mivacurium

Depolarising blockers SUCCINYL CHOLINE /

SUXAMETHONIUM:

Only depolarising SMR in use at present

Resembling 2 molecules of Ach joined

together

Stimulates Nm receptors- depolarisation of

membrane. It is responsible for initial

fasciculations (post op muscle pain or

soreness)

Constant depolarisation makes end plate

refractory to other impulses and muscle

relaxation results

It is a type of flaccid paralysis that

cannot be reversed with neostigmine

(phase I block)

On prolonged use, membrane

becomes desensitized which leads to

phase II block that can be reversed

with anticholinesterases.

It potentiates its effects

Pharmacological actions On iv administration, onset is rapid

within 1 min.

Initial transient muscular fasciculations and twitchings mostly in the chest and abdominal regions are followed by skeletal muscle paralysis

Fasciculations are due to stimulation of muscle fibers by the discharge of action potential (max 2mins & subside in 5 mins)

SA- given continuously as an infusion for longer effect

CVS

Initially hypotension and bradycardia

due to stimulation of vagal ganglia

Followed by hypertension &

tachycardia due to stimulation of

sympathetic ganglia

Higher doses cause cardiac

arrythmias

Cause histamine release if injected

rapidly

Preferred SMR for endotracheal

intubation

Pharmacokinetics

Rapidly hydrolysed by

pseudocholinesterase (about 3-8 mins)-

Shortest A & fastest acting

Transient apnoea is usually seen at peak

of its action

In people with liver disease or atypical

pseudo cholinesterase due to genetic

defect, metabolism of Sch becomes slow

which results in severe neuromuscular

blockade leading to respiratory paralysis

& apnoea- succinyl choline apnoea

Adverse reactions

Muscle pain due to initial fasciculations

Hyperkalaemia- esp. in nerve and

muscle disorders. dangerous

particularly in CCF patients.

Cardiac arrythmias

Increases all pressure- IOP, intracranial

pressure, blood pressure due to

stimulation of sympathetic ganglia and

intragastric pressure responsible for

nausea & vomiting

Malignant hyperthermia Rare genetically determined condition

where there is a sudden increase in body temperature & severe muscle spasm due to release of intracellular Ca++ from the sarcoplasmic reticulum

Drugs like halothane, isoflurane, sevoflurane, Sch can trigger the process. Combination of these anaesthetics with Sch is fatal.

IV dantrolene –DOC

Rapid cooling, inhalation of 100% oxygen & control of acidosis

Contraindications

Nerve diseases- paraplegia, hemiplegia,

Guillain barre syn

Muscle diseases- muscular dystrophy,

myasthenia gravis, crush injury, burns,

rhabdomylosis

Glaucoma

Head injury

Non depolarising blockers

Competetive blockers

Competetively inhibit Nm receptors- block

actions of Ach- cause muscle relaxation

without any fasciculations

These compounds slowly dissociate from

the receptors & transmission is gradually

restored.

Reversed by anticholinesterases

d- Tubocurarine

Curare was used by the indeginous

South Americans as arrow poison for

hunting animals because curare

paralysed animals

Natural sources- Strychnos toxifera,

Chondrodendron tomentosum

Active principles- tubocurarine, toxiferins

Not absorbed orally because of too large

& highly charged to pass through lining

of digestive tract

Benjamin collins- curare did not kill the

animal & recovery is complete is

respiration is maintained artificially

Charles waterton- curarized female

donkey alive by artificial respiration by

tracheostomy

Claude Bernard- NMJ

Pharmacological actions &

Flaccid paralysis- small muscles of the

eyes and fingers are the first to be

affected, followed by those of the

limbs, neck and trunk later intercostal

muscles, and finally diaphragm.

Recovery occurs in the reverse order.

Consciousness and appreciation of

pain are not affected

In high doses tubocurarine can block

autonomic ganglia and adrenal

medulla resulting in hypotension

Histamine release (d-TC, mivacurium,

atracurium) hypotension,

bronchospasm, increased

tracheobronchial and gastric

secretion, hypotension

Release HT by Direct effect on mast

cells

Cardiovascular collapse, tachycardia

Hypotension

Respiratory paralysis

Bronchospasm, flushing- not seen with

newer agents

Aspiration of gastric contents

Treatment of toxicity:

Neostigmine/ pyridostigmine - antidote

Antihistamines should be given to

counter the side effects of histamine

Adverse effects

Rocuronium- fastest acting DSMR. Used

as an alternative to Sch for rapid

sequences of endotracheal intubation

Rapacuronium- fastest acting.

Withdrawn due to reports of severe

bronchocontriction

Vecuronium- preferred in cardiac

patients because of better cardiovascular

stability, contraindicated in hepatic

disease and biliary obstruction

Doxacurium- most potent & longest

acting

Mivacurium- shortest acting. Alt to Sch

Atracurium & cis-atracurium – agents of

choice for patients with hepatic or renal

insufficiency. Cis-atracurium- much less

histamine release (hoffman’s

elimination)

Gantacurium- undergoing phase III

clinical trials- fastest & shortest acting.

Alt to Sch

Gallamine- least potent. Rarely used

because of nephrotoxic & terotogenic

potential, tachycardia

Drug interactions

Antagonist: Anticholinesterases like

physostigmine, neostigmine

Agonistic: General anaesthetics like

halothane, isoflurane

CCBs- verapamil, diltiazem

Antibiotics: aminoglycosides,

tetracyclines, polypeptides

Uses

Adjuvant to anaesthesia: -for producing

satisfactory skeletal muscle relaxation

during surgical procedures

In minor procedures- laryngoscopy,

bronchoscopy, tracheal intubation,

orthopaedic procedures like reduction of

fracture dislocations

In electro convulsive therapy to prevent

trauma

Spastic disorders- tetanus, athetosis

Status epilepticus

Ventilatory support- to reduce

resistance of the chest wall and

enhance thoracic compliance to

facilate artificial ventilation in ICUs