SKELETAL MUSCLE RELAXANTS

SKELETAL MUSCLE RELAXANTS

·         These agents possess structural group that allow interaction with nicotinic cholinergic receptors (N_M)

Classification

1.      Non-depolarizing / competitive N_M blocker

Long acting – d-tubacurarine, Pancuronium, Gallamine

Intermediate acting – Atracurium, Vencuronium

Short acting – Mivacurium

2.      Depolarizing non-competitive N_M blocker

Suxamethonium, Decamethonium

Non-depolarizing / competitive N_M blocker

·         These agents combine with nicotinic receptors in the N_M junction and prevent the binding of Ach.

·         Binding of the Ach with the nicotinic receptors cause opening of sodium ion channels allowing depolarization of muscle membrane and contraction of skeletal muscle normally.

·         Occupation of these sites by the N_M blockers do not allow conformational change in the nicotinic receptors needed for opening of the channel and subsequent depolarization of the membrane and muscle contraction. They lack intrinsic activity.

·         As it is a competitively blocking, their actions overcome by increasing the Ach concentration i.e., by administering the Ach esterase enzyme inhibitors like Neostigmine.

d-tubacurarine

·         This drug is the prototype of  competitive N_M blocker

·         Curare is a generic term applied to many plant extract used by South American tribal as arrow poison for game hunting.

·         Muscles that sub serve very fine movements are more sensitive than stronger muscle showing course movement.

·         Extraoccular muscles are affected first followed by face, limb and trunk and then intercostals muscles and finally diaphragm. Recovery is in the reverse order.

·         Pain is felt and consciousness present.

·         Cause histamine release from mast cells by direct action.

·         At clinical doses there is a partial blockade at ganglia and adrenal medulla on N_N  receptors.

·         On rapid intravenous administration hypotension and tachycardia noticed.

·         Bronchoconstriction occurs due to histamine release.

·         Not used in hepatic and renal failure patients and in tachycardia condition. Used with caution in Myasthenia gravis condition.

·         Aminoglycosides inhibit the Ach release from cholinergic nerve terminals by competing with calcium ions. Hence they enhance the N_M blockade.

·         When these groups of drugs are administered along with Calcium channel blockers or general anaesthetics, the N_M blocking effect is enhanced.

 Clinical use

·         As preanaesthetic medication

·         To reduce severity of spasm in tetanus

·         For orthopedic manipulation and fracture reduction.

Pancuronium

·         Five times potent than d-tubacurarine

·         It will not have any action on autonomic ganglia and adrenal medulla

·         It does not release histamine form mast cell

·         Only mild side effect noticed

·         Used as an adjunct to general anaesthesia.

·         Inexpensive, so widely used in Veterinary medicine.

Gallamine

·         Less potent than d-tubacurarine

·         Occasionally used to capture exotic species (Crocodiles) often needs reversal and seldom used in Veterinary practice.

Vencuronium

·         It will not have any action on autonomic ganglia and adrenal medulla

·         It does not release histamine form mast cell

·         Good muscle relaxant with regard to CNS stability.

Atracurium

·         Four times less potent than pancuronium

·         It has unique property that its molecules undergo spontaneous breakdown due to temperature and pH dependant process – Hoffmann elimination

Mivacurium

·         More potent than atracurium

·         Mild histamine releaser

·         It does not need reversal agent.

Depolarizing N_M blocking drugs

Depolarizing N_M blocker attach with the N_M receptor

Depolarize post junctional membrane by opening sodium ion channel

(having affinity and intrinsic activity)

The drug attach to receptor for longer period

 

Constant stimulation results in persistent depolarization

Repetitive excitation and transient muscle fasciculation (Phase I)

Continued binding of drug

 

Incapable of transmitting further impulse

 

Closure of sodium ion channel

 

Repolarization despite continuous presence of drug

 

Resistant to further depolarization

Flaccid paralysis (Phase II)

Suxamethonium

·         It is an ultra short acting drug. The duration varies with species, 3 min in pig and 30 min in dog.

·         Muscle fasciculation noticed prior to muscle relaxation. Without analgesia it will be painful to bear the fasciculation.

·         Neostigmine and Aminoglycoside potentiates its action and prolongs the recovery.

·         Does not block ganglia except in high dose and it is a weak histamine releaser.

·         It increases intraocular pressure due to prolonged contraction of Extraoccular muscles.

·         It is metabolized by plasma pseudocholine esterase enzyme.

Clinical use

·         Facilitate endotracheal intubation in pigs, cats and primates.

·         Used for short term muscle relaxation for surgical and diagnostic purpose.

Dexamethonium

·         Actions similar to Suxamethonium

·         Long acting when compared to suxamethonium.