non-depolarising neuromuscular blockers
Quite opposite to the depolarising neuromuscular blockers, these agents act as antagonists at nicotinic acetylcholine receptors at neuromuscular junction.
This class includes various drugs like
Note: Gallamine is a neuromuscular blocker as well as muscarinic blocker leading to tachycardia. Nowadays its use is declined due to availability of alternative agents.
The first drug in this category is d-tubocurarine. It is a natural alkaloid obtained from dried bark and stem of Chondodendron tomentosum. The dextro isomer of the compound has skeletal muscle relaxant activity. The drug is a quaternary ammonium compound hence ionized and can’t cross the blood brain barrier. Therefore is shows only peripheral actions.
In ancient days, it is usually coated at the tip of the arrow which when pierces into animal skin paralyses skeletal muscle of animal preventing its escape. Hence it is called as arrow poison.
d-tubocurarine also shows action at ganglia and mast cells. Ganglionic block produces hypotension which is further increased by histamine release. Histamine release also leads to bronchoconstriction.
Unlike depolarising neuromuscular blockers, they don’t produce any initial muscle fasciculations and postoperative pain.
Gallamine is a partial M2 antagonist and neuromuscular blocker. Due to its antimuscarinic effects it produces tachycardia hence nowadays it is less preferred.
Drugs ending with suffix curnoium are structural derivatives of curarae alkaloids. Pancuronium is one of the drugs in this category that is again bis quaternary compound but with steroidal ring. It has two advantages over tubocurarine.
- Fast onset of action
- No hypotension and bronchoconstriction
Still it produces the following disadvantages such as
- Long acting
- Produces tachycardia
So the muscle relaxation produced by pancuronium is long lasting and not recovered even after surgery. Vecuronium and rocuronium are the next derivatives with fast onset and medium duration of action. They also have less chance of producing tachycardia hence more preferred.
These are short acting neuromuscular blockers. Cisatracurium is a cis-isomer of atracurium.
Atracurium is intentionally prepared as short acting. The injection of this drug is kept at acidic environment where it is highly stable. Once injected into the body it is fragmented due to change in the pH thereby shows its acting for very short period.
Mivacurium is another short acting neuromuscular blocker that undergoes rapid hydrolysis by plasma cholinesterases.
Note: Compare it with succinylcholine. Both the drugs are short acting due to hydrolysis by plasma cholinesterase. But succinylcholine is a depolarising and mivacurium is a non-depolarising neuromuscular blocker.