Tubocurarine -Non-depolarizing Neuromuscular Blocker

Tubocurarine is a non-depolarizing neuromuscular blocker. Non-depolarizing neuromuscular blockers interfere with the NM transmission. D-tubocurarine is a natural substance, obtained from curare, which was used in ancient times as an arrow head poison to kill animals. Source of curare is ‘Chondrodendron Tomentosum’ and Strychnas.

Chemistry

It is a quaternary compound.

Mechanism of Action

It competes with acetylcholine for post-synaptic nicotinic NM receptors and blocks them.

No flow of ions occurs, thus there is no contraction.

This blockage is competitive and reversible, the sequence of events for this blockage are:

1. Muscles capable of rapid movements like fingers, toes, eyes and jaw muscles are the first to go.

2. Muscles of neck, limbs and trunk are second to go.

3. Respiratory muscles, intercostal muscles and diaphragm at last. (Diaphragm paralyzes last and is the first to recover)

The recovery occurs in the opposite manner.

Pharmacological Actions

Release of histamine (premedication with antihistaminics is useful, otherwise hypotension might occur)
Causes weak blockage of ganglion
Blocks adrenal medulla

Over dosage

The effect of this drug can be antagonized by anticholine esterases e.g. neostigmine given in a dose of 1-2 mg I/V. Neostigmine is combined with atropine to block muscarinic effects.

Atropine has biphasic effect on heart, gives first bradycardia then tachycardia, so given shortly before neostigmine to prevent activation of cardiac muscarinic receptors.

Pharmacokinetics

Cannot of given orally is quaternary compound. If given orally, no absorption occurs. By I/V it is excreted as such in urine. Onset of action is 4-5 minutes. Duration of action is 30-60 minutes. Short duration is due to redistribution and not due to diminution. That is why it should not be given repeatedly; otherwise it will accumulate in fat tissue and cause toxicity.

Therapeutic Uses

Skeletal muscle relaxant for endotracheal intubation.
When this drug is used with general anesthetics, lesser dose of general anesthetics is required.
Used in chest crush injuries to relax chest muscle.
Given in convulsions
Is an antidote for strychnine poisoning

Adverse Effects

Hypotension (because of histamine release and ganglion blockage, vasodilatation)
Bronchospasm (histamine release)
Rash (histamine)
Vomiting (paralysis of sphincters and diplopia can be there due to paralysis of muscles)