L.K.G. Vimal and O.O. Oladapo,
Abmadu Bello Teaching Hospital, Zaria, Nigeria.

Mechanism of Action		Pancuronium
Tubocurarine		Atracurium
Gallamine		Vecuronium
Alcuronium		General Considerations

Mechanism of action

Non-depolarising muscle relaxant drugs (NDMRD) compete with acetyl choline (ACh) molecules released at the neuromuscular junction to bind with the ACh receptors on the post synaptic membrane of the motor endplate. They therefore block the action of ACh and prevent depolarisation (or activation) of the muscle contraction process. Muscle groups differ in their sensitivity to muscle relaxants; ocular muscles responsible for opening and moving the eyes are the most sensitive followed by the muscles of the jaw, neck, limbs, intercostals and abdomen. The diaphragm is the least sensitive muscle, which is why patients undergoing surgery sometimes hiccup or breathe as an early sign that the relaxants are wearing off.

Non-depolarising muscle relaxant drugs also act on presynaptic receptors interfering with the entry of calcium which causes an inhibition in the release of ACh. Other drugs such as the aminoglycoside antibiotics (eg gentamicin) and volatile agents may also effect this mechanism and increase sensitivity to relaxants.

A variety of relaxant drugs are in use in different parts of the world. All produce profound muscle paralysis but have varying effects on the autonomic nervous system. None of the drugs cross the blood brain barrier as they are water soluble, polar molecules and therefore have no effect on the central nervous system. All non depolarising drugs should be used with care in patients suspected to be suffering with myasthenia gravis or myasthenic syndrome as patients with these conditions are extremely sensitive to their effects.

The commonly used drugs are summarised below.

 
Tubocurarine (Curare, d-tubocurarine) is a naturally occurring drug which takes about 3 minutes to act when given intravenously and lasts for 30-40 minutes.

Cardiovascular effects: Curare has no direct action on the heart but there is often a slight fall in the blood pressure secondary to a vasodilating effect via the sympathetic ganglia. In the presence of volatile agents the blood pressure fall may be greater. Care should be taken with this combination in hypotensive patients.

Respiratory effects: Curare has occasionally been associated with bronchospasm due to the release of histamine. It should be used with caution in asthmatic patients.

Histamine release may occur following the administration of curare and frequently presents as a red weal in the line of the vein which has been used for the injection. Problems associated with this reaction are very rare.

Placental transfer is not a feature of curare and the drug may be safely used in obstetrics.

Effect of metabolic abnormalities: Curare is potentiated by the presence of respiratory acidosis and hypokalaemia.

Distribution, metabolism and excretion: Thirty to forty percent is excreted unchanged in the urine and most of the remainder in the bile. In renal failure the drug is excreted effectively by the biliary route provided large or repeated doses are avoided.

Dose, administration and use: The initial dose should be 0.3-0.6mg/kg followed by supplementary doses of 5mg when required (usually after 20-30 minutes). Neonates (less than 1 month old) are sensitive to curare and an initial dose of 0.3mg/kg is recommended.

Storage: Curare does not need to be refrigerated.

 
Gallamine (Flaxedil) is a synthetic (manufactured) drug which acts 1-2 minutes after i.v. injection and lasts 20-30 minutes.

Cardiovascular effects: Gallamine produces an increase in heart rate, usually by 20-30 beats/minute due to an inhibitory action on the vagal supply to the heart. Blood pressure is usually unaltered unless bradycardia was previously present.

Histamine release is very rare.

Placental transfer: Gallamine is thought to cross the placenta more than other relaxants although it has been used successfully for Caearean section.

Effect of metabolic abnormalities: Gallamine is potentiated by alkalosis and antagonised by acidosis.

Distribution, metabolism and excretion: Gallamine is excreted almost entirely by the kidneys and should be avoided in patients with renal impairment.

Dose, administration and use: A dose of 1.5-2mg/kg is effective in 1-2 minutes and lasts for 15-30 minutes. Supplementary doses are usually 20 mg.

Storage: Gallamine does not require refrigeration.

 
Alcuronium (Alloferin) is a semi-synthetic muscle relaxant which has many similarities with curare. It is slightly shorter acting than curare.

Cardiovascular effects: After an i.v. dose there is frequently a slight fall in blood pressure due to vasodilation secondary to a degree of sympathetic blockade. This is occasionally accompanied by a tachycardia. Alcuronium is associated with a slightly higher incidence of anaphylactoid reactions than other non-depolarising muscle relaxants.

Placental transfer: Alcuronium does not cross the placenta in appreciable amounts and has been widely used in obstetrics.

Distribution, metabolism and excretion: Most of the drug is excreted unchanged in the urine although some is also excreted in the bile. When used in patients with renal or hepatic impairment the dose should be reduced.

Effect of metabolic abnormalities: Mild acidosis or alkalosis does not alter the duration of action of alcuronium.

Dose, administration and use: Although there is some variation in requirements between patients an initial bolus of 0.2-0.3mg/kg is usually sufficient to provide relaxation for 20-40 minutes. Further increments should be with 15-25% of the original dose. It is potentiated by halothane. In children some anaesthetists recommend using doses of 0.125-0.25mg/kg. Always allow at least 20 minutes following the last dose before attempting to reverse the patient.

Storage: Alcuronium should be stored below 25 degrees centigrade and be protected from light.

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