ATRACURIUM BESYLATE

By- Anita.F.Lopes

ATRACURIUM BESYLATEDrug Category

Neuromuscular Non-depolarizing Agents (intermediate-duration)

Nicotinic Antagonists

NORMAL PHYSIOLOGYAcetyl Coholine: a neurotransmitter which

acts on cholinergic receptors Cholinergic Receptors (Protein based

receptors) are of two types:- 1) Nicotinic Acetyl Coholine

Receptor: (Ionotropic receptor) 2) Muscurinic Acetyl Coholine

Receptor (Metabotropic receptor): Responds to Muscurine

It has G-Protein receptor complex in the cell membrane of certain neurons

Muscarine, L-(+)-muscarine, or muscarin is a natural product found in certain mushrooms.

Muscarine mimics the function of the natural neurotransmitter acetylcholine in the muscarinic part of the cholinergic nervous system.

NEUROMUSCULAR BLOCKING AGENTS

Non-depolarizingBind to cholinergic receptors and prevent acetylcholine (Ach) from stimulating receptorsEg: Curare (alkaloid arrow poison: blocks nicotinic receptors )Effect: compete with Ach for nicotinic receptor binding sites.

The blockade is competitive, hence muscle paralysis occurs gradually.

NEUROMUSCULAR BLOCKING AGENTS

Depolarising:Produce what appears to be a "persistent" depolarisation of the NMJ.

Cause depolarisation by mimicking the effect of Ach but

without being rapidly hydrolysed by acetylcholinesterase. Propagation of an action potential is prevented by the

area of inexcitability that occurs around the Ach receptors.

Examples include suxamethonium (1951) and decamethonium (1948)Model = succinylcholine (Nicotinic Ach Receptor agonist causes persistent depolarisation at motor end plate…transient fasciculations and then paralysis

Action occurs in two phases:

 Phase I - initial brief depolarisation of post-junctional membrane skeletal muscle, thus causing contraction; fasciculations are seen and repolarisation is inhibited

 Phase II-"desensitisation blockade"

After the drug has been present for a period of time, the motor end plate loses its sensitivity and depolarisation cannot occur; desensitisation continues for several minutes, even after drug is no longer present.

Depolarising NMJ blockers produce persistent depolarisation = desensitisation

Fasciculations can be prevented by pretreatment with a competitive agent.

INDICATIONS Adjunct to anesthesia to facilitate

endotracheal intubation   To provide skeletal muscle relaxation

during surgery or mechanical ventilation.

CONTRAINDICATIONS Known to have a hypersensitivity

TRACRIUM from multiple-dose vials containing benzyl alcohol as a preservative is contraindicated in patients with a known hypersensitivity to benzyl alcohol.

COMPLICATIONS Histamine release Effects of histamine release:

- bronchospasm- dilatation of peripheral blood vessels (decreased blood pressure)- excessive secretions -anticoagulant effect 

Interactions of NMJ blockers 

Blockade is potentiated with general inhalational anaesthetics; antibiotics,

e.g. gentamycin (decrease Ach release) and tetracyclines (chelate calcium and decrease Ach release).Blockade is reduced with anticholinesterase agents. Results in increased Ach levels at the NMJ, thus antagonising the effects of competitive agents.

MECHANISM OF ACTION Inducing: Atracurium antagonizes the

neurotransmitter action of acetylcholine (An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of acetylcholine, aneurotransmitter) by binding competitively with cholinergic receptor sites on the motor end-plate.

Reversal: This antagonism is inhibited, and neuromuscular block reversed, by acetylcholinesterase inhibitors such as neostigmine, edrophonium, and pyridostigmine.

DRUG INTERACTION Enhances the neuromuscular blocking action of

TRACRIUM include: enflurane; isoflurane; halothane; certain antibiotics, especially the aminoglycosides and polymyxins; lithium; magnesium salts; procainamide; and quinidine.

If other muscle relaxants are used during the same procedure, the possibility of a synergistic or antagonist effect should be considered.

TRACRIUM should not be administered until a patient has recovered from succinylcholine-induced neuromuscular block, because the prior administration of succinylcholine does not enhance the duration, but quickens the onset and may increase the depth, of neuromuscular block induced by TRACRIUM.

TOXICITY Excessive doses can be expected to

produce enhanced pharmacological effects.

Over dosage may increase the risk of histamine release and cardiovascular effects, especially hypotension.

Amanita muscaria, the mushroom from which muscarine was isolated.