I/V MUSCLE RELAXANTS

DR.ZAHID AZIZDEPARTMENT OF ANAESTHESIOLOGY SICU AND PAIN MANAGEMENT CIVIL HOSPITAL KARACHI

INTRODUCTIONMuscle relaxants are the agents that

act peripherally at neuromuscular junction/muscle fibre itself to block neuromuscular transmission.

In order to facilitate muscle relaxation for surgery & for mechanical ventilation during surgery or in ICU.

SITE OF ACTION OF MUSCLE RELAXANTS Muscle relaxants blocks nicotinic receptor

of Acetylcholine peripherally at the neuromuscular junction.

Mainly at postjunctional receptors. Either acting as agonist(depolarizing) or

antagonist(non-depolarizing).

TYPES OF MUSCLE RELAXANTS

NON-COMPETITIVE(DEPOLARIZING) SUCCINYLCHOLINE DECAMETHONIUM (No longer available)

COMPETITIVE(NON-DEPOLARIZING) ATRACURIUM CISATRACURIUM ROCURONIUM PANCURONIUM VECURONIUM MIVACURIUM

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SUCCINYLCHOLINE STRUCTURE: Consists of two joined acetylcholine

molecules MECHANISM OF ACTION: Succinylcholine act like

acetylcholine but persist at the synapse at high concentration and for longer duration and constantly stimulate the receptor.

First, opening of the Na+ channel occurs resulting in depolarization, this leads to transient twitching of the muscle, continued binding of drugs make the receptor incapable to transmit the impulses, paralysis occurs.

The continued depolarization makes the receptor incapable of transmitting further impulses.

SUCCINYLCHOLINE INDICATIONS: Patient with full stomach. Obstetric patient. Anticipated difficult intubation. DOSE: Intubating 1.0-1.5mg/kg. ONSET OF ACTION: 30-60 seconds DURATION OF ACTION: Less than 10 mins. METABOLISM: By Plasmacholinestrase or

Butrylcholinestrase or Pseudocholinestrase.

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SUCCINYLCHOLINE

Succinylcholine on breakdown by butrycholinesterase produces succinylmonocholine.

The duration of action is prolonged by high dose or by abnormal metabolism.

Abnormal metabolism may result from hypothermia, low enzyme levels or genetically aberrant enzyme.

Hypothermia decreases rate of hydrolysis.

SUCCINYLCHOLINE Low levels of pseudocholinesterase accompany liver disease,carcinomatosis and

starvation,pregnancy,anticholinestrases,hypothyroidism,renal disease.

Prolonged paralysis caused by atypical cholinesterase should be treated with cont mechanical ventilation until muscle function returns to normal.

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SIDE EFFECTS OF SUCCINYLCHOLINE

Bradycardia preventable by atropine.

Hyperkalemia in patients with massive trauma,burns,stroke,tetanus,closed head injury.

Muscle pain. Fasciculations. Intragastric pressure elevation. Intraocular pressure elevation. Malignant hyperthermia. Prolonged paralysis (Succinylcholine apnea). Intracranial pressure elevation.

MECHANISM OF ACTON:MECHANISM OF ACTON: • These have an affinity for the Nicotinic (NM)

receptors at the muscle end plates but have no intrinsic activity.

• The antagonism is surmountable by increasing the conc. of Ach.

NON-DEPOLARIZING AGENTS

Non depolarising neuromuscular blocking drugs classification (on basis of chemical strucure)

Benzylisoquinolinium (Release histamine)

D-tubocurarineMetocurineDoxacuriumAtracuriumCisatracuriumMivacurium

Aminosteroids (Not release histamine)

PancuroniumVecuroniumRocuroniumRapacuronium

ATRACURIUM Benzylisoquinoline derivative Intubating dose 0.5mg/kg. Onset of action 2.5-3.0 mins. Duration of intubating dose 30-45 mins. Maintenance by boluses 0.1mg/kg. May release histamine and may therefore can cause

hypotension,tachycardia,bronchospasm. Non-organ dependent elimination

Non specific estererase: 60% of elimination Hofmann elimination : spontaneous nonenzymatic chemical breakdown occurs at physiologic pH and

temperature.

ATRACURIUM

Laudanosine toxicity-breakdown product from Hofmann elimination, assoc. with central nervous system excitation resulting in elevation of MAC and precipitation of seizures.

Temperature and pH sensitivity-action markedly prolonged in hypo- thermic or acidotic patients.

Available as a solution of 10mg/ml.It must be stored at 2-8 centigrade.At room temperature,it should be used within 14 days to preserve potency.

CIS-ATRACURIUM Benzoisoquinoline derivative Intubating dose 0.2mg/kg Onset 2-3 mins. Duration of intubating dose 40-75 mins. 3x more potent than atracurium. No ester hydrolysis. More hoffman degradation. Produces less laudanosine. Minimal histamine release Useful in critically ill patient requiring prolonged infusion of

neuromuscular blocking drugs.

MIVACURIUM Benzylisoquinoline derivative. Potency, 1/3 that of atracurium Metabolized by plasma cholinestrase at 88% of the

rate of succinylcholine. Intubating dose 0.1-0.15 mg/kg Onset of action 2.5-3.0 mins (similar to atracurium). Duration of intubating dose 15-20 mins (recovery faster

than atracurium). Produces similar amount of histamine release to

atracurium.

MIVACURIUM Useful particularly for surgical procedures

requiring muscle relaxation in which even atracurium and vecuronium seem too long-acting and when it is desirable to avoid side effects of succinylcholine e.g. for bronchoscopy,esophagoscopy or tonsillectomy.

Duration of action may be increased due to reduced plasma cholinestrease activity because of either inherited or acquired factors.

PANCURONIUM Bisquaternary aminosteroid muscle relaxant. Intubating dose 0.08-0.12mg/kg. Onset 2-3 mins. Duration of intubating dose 60-120 mins. The clinical duration of action is long,especially in the

presence of potent inhalational agents or renal dysfunction as 60% of dose of drug excreted unchanged through the kidneys.

Does not stimulate release of histamine. Direct vagolytic and sympathomimetic effects which may

cause tachycardia and hypertension

VECURONIUM Monoquaternary aminosteroid. Developed in an attempt to reduce the cardiovascular

effects of pancuronium. Intubating dose 0.1mg/kg. Onset 2-3 mins. Duration of intubating dose 45-90 mins. Depends primarily on biliary excretion secondarily on

renal excretion. Does not have any direct cardiovascular effects although

potentiation of opioid induced bradycardia may be seen.

ROCURONIUM Monoquaternary aminosteroid analogue of

vecuronium designed to provide rapid onset of action.

Intubating dose 0.45-0.9 mg/kg. Onset 60-90 seconds. Duration of intubating dose 35-75 mins. Suitable alternative for rapid sequence

inductions but at the cost of a much longer duration of action.

ROCURONIUM Stimulates little histamine release or

cardiovascular disturbance. Mild vagolytic property in high doses which

sometimes causes tachycardia. Excreted unchanged in the urine and in the bile

and thus the duration of action may be increased by severe renal or hepatic dysfunction.

Rocuronium has no metabolites with significant neuromuscular blocking activity.