MUSCLE RELAXANTS

Mr. D.Raju, M.pharm,Lecturer

Muscle Relaxants are classified as:I)Peripherally acting

A.Neuromuscular blocking agents:-1) Depolarizing muscle relaxants.2) Non-depolarizing muscle relaxants

B.) Directly acting: Dantrolene, QuinineII)Centrally acting

o Chlorzoxazone,Chlormezanone, Diazepam, Baclofen, Tizanidine, Metaxalone.

Depolarizing Muscle relaxants:Succinylcholine (short acting)

Non-depolarizing Muscle relaxants:Short acting:

MivacuriumIntermediate –acting:

Atracurium,Cisatracurium,Vecuronium,Rocuronium

Long acting :DoxacuriumPancuroniumPipecuronium

MECHANISM OF ACTION

SUXAMETHONIUM:• Block transmission by causing prolonged

depolarization of endplate at neuromuscular junction.

• Manifestation by initial series of muscle twitches (fasciculation) followed by flaccid paralysis.

• It immediately metabolize in plasma by Pseudo-cholinesterase which is synthesized by liver so to prevent its metabolism in plasma it should be given at faster rate.

SYSTEMIC EFFECTSCardiovascular: Produces muscarinic effects as acetylcholine , therefore causes bradycardia ( but when given high doses causes tachycardia because of stimulation of nicotinic receptors at sympathetic ganglions.)Hyperkalemia: Occurs due to excessive muscle fasciculations. Ventricular fibrillation can occur due to hyperkalemia.CNS: Increases intracranial tension ( due to contraction of neck vessels)Eye: Increases intraocular pressure.

GIT: Increases intra-gastric pressure , salivation, peristalsis.Muscle pains ( myalgia): This is a very common problem in post operative period. These are due to excessive muscle contractions.Malignant hyperthermiaSevere AnaphylaxisMasseter Spasm : Sch can cause masseter spasm especially in children & patients susceptible for malignant hyperthermia.

Doesnot require reversal rather cholinesterase inhibitors (neostigmine) can prolong the depolarizing block (because these agents also inhibits the pseudocholinesterase)

CONTRAINDICATIONSHyperkalemia: Serum K > 5.5 is an absolute contraindication for use of Sch.Head Injury : It increase ICPNewborns and infants: These have extrajunctional receptors which are sensitive to depolarizing agents & Sch can produce severe hyperkalemia by interacting with these receptors.Glaucoma & eye injuries.Up to 2-3 months after trauma, Up to 6 months after hemiplegia/paraplegia, Up to 1

Renal Failure : If associated with hyperkalemia.

Prolonged intra abdominal infection can be associated with hyperkalemia.Diagnosed case of atypical pseudocholinesterase & low pseudocholinesterase.Duchene muscular dystrophyDystrophia myotonica: Permanent contractures may develop if SCh is given in these patients.Tetanus.Gullian Barre SyndromeMetabolic Acidosis :Acidosis is associated with hyperkalemia.Shock : It is associated with acidosis which in turn is associated with hyperkalemia.Spinal cord injury.

NON-DEPOLARIZING MUSCLE RELAXANTS:Mechanism of action:

• It blocks nicotinic receptors competitively resulting in inhibition of sodium channels and excitatory post-synaptic potential.

• It binds at the same site at which acetylcholine binds.

• All NDMR are quarternary ammonium compounds & highly water soluble i.e. hydrophilic. So, they do not cross blood brain barrier & placenta except Gallamine.

BROAD CLASSIFICATION

These are broadly divided into steroidal compounds and benzylisoquinoline (BZIQ) compunds.STEROIDAL COMPOUNS: (vagolytic properties)

It includes PANCURONIUM,VECURONIUM , PIPECURONIUM,ROCURONIUM, RAPACURONIUM.BZIQ(Benzylisoquinoline): (hystamine realease)

It includes d-Tubocurare, Metocurine, Doxacurium, Atracurium, Mivacurium,

STEROIDAL COMPOUNDSPancuronium(PAVULON)

Very commonly used as it is inexpensive.It releases noradrenaline & can cause tachycardia & hypertension. Because of this there are increased chances of arrhythmia with halothane

PipercuroniumIt is a pancuronium derivative with no vagolytic activity, so cardiovascular stable, slightly more potent

Vercuronium (Norcuron)It is very commonly used now a days. It is cardiovascular stable. Shorter duration of action.It is the muscle relaxant of choice in cardiac patient.

Rocuronium8 times more potent than vecuronium and it also has earlier onset of actionBecause of onset comparable to succinylcholine it is suitable for rapid sequence intubation as an alternative to succinylcholine.

BENZYLISOQUINOLINE COMPOUNDS

D- TubocurareIt is named so because it was carried in bamboo tubes & used as arrow poison for hunting by Amazon people.It has highest propensity to release histamineIt causes maximum ganglion blockade. Because of ganglion blocking & histamine releasing property it can produce severe hypotension.

CENTRALLY ACTING MUSCLE RELAXANTS

These are drugs which produce muscle relaxation through central mechanism both at supraspinal & spinal levelPolysynaptic reflexes involved in maintenance of muscle tone are inhibited at both spinal & supraspinal level. It also produces sedation

UsesMuscle spasms.Tetanus : IV diazepam is most effective.Spastic neurological diseases like cerebral palsy,Spinal injuries.

REVERSAL OF BLOCK

Drugs used for reversal of block are cholinesterase inhibitors (anticholinesterases).Reversal should be given only after some evidence of spontaneous recovery appear.

Mechanism of ActionIt inactivate the enzyme acetylcholinesterase which is responsible for break down of actetylcholine, thus increasing the amount of acetylcholine available for competition with non depolarizing agent thereby re-establishing neuromuscular transmission.Anticholinesterases used for reversal are:

NeostigminePyridostigmineEdrophoniumPhysostigmine

These agents except physostigmine are quarternary ammonium compounds so they do not cross blood brain barrier.The biggest disadvantage is that these agents also increase the acetylcholine level at muscarinic receptors producing muscarinic side effects like bradycardia, bronchospasm.So, to prevent these muscarinic effects some anti cholinergic like atropine or glycopyrrolate is to be given with cholinesterase inhibitors.

Neostigmine : Anticholinergic preferred with it is glycopyrrolate because both have same onset of action (both are slow acting).

Edrophonium : Anticholinergic preferred with it is atropine (both fast acting).

Pyridostigmine: It is preferred drug for renal failure patients in whom a prolonged stay of muscle relaxant is expected.

DRUGS WHICH ANTAGONISE NEUROMUSCULAR BLOCKADE

They reverse the block by NDMR onlyPhenytoin Carbamazepine CalciumCholinesterase inhibitorsAzathioprineSteroids.