MUSCLE RELAXANTS

1. MUSCLE RELAXANTS

2. Muscle Relaxants are classified as: I)Peripherally acting A.Neuromuscular blocking agents:- • Depolarizing muscle relaxants. • Non-depolarizing muscle relaxants B.) Directly acting: Dantrolene, Quinine II)Centrally acting • Chlorzoxazone,Chlormezanone, Diazepam, Baclofen, Tizanidine, Metaxalone.

3. Depolarizing Muscle relaxants: • Succinylcholine (short acting) Non-depolarizing Muscle relaxants: Short acting: • Mivacurium Intermediate –acting: • Atracurium, • Cisatracurium, • Vecuronium, • Rocuronium Long acting : • Doxacurium • Pancuronium • Pipecuronium

4. 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.

5. Systemic effects • Cardiovascular: 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.

6. 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 hyperthermia • Severe Anaphylaxis • Masseter 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)

7. CONTRAINDICATIONS • Hyperkalemia: Serum K > 5.5 is an absolute contraindication for use of Sch. • Head Injury : It increase ICP • Newborns 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 year after burns. In these conditions the denervated/regenerating nerve develops extra junctional receptors which can produce hyperkalemia.

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

9. 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.

10. 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, Cisatracurium • OTHERS includes Gallamine, Alcuronium

11. Differences between Depolarizing & Non-depolarizing block

12. NDMR are used in anaesthesia for: • Maintenance of anaesthesia. • For intubation where succinylcholine is contraindicated ( Rocuronium is of choice) • For precurarization to prevent postoperative myalgias by succinylcholine.

13. STEROIDAL COMPOUNDS Pancuronium(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 Pipercuronium • It 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. Rocuronium • 8 times more potent than vecuronium and it also has earlier onset of action • Because of onset comparable to succinylcholine it is suitable for rapid sequence intubation as an alternative to succinylcholine.

14. Benzylisoquinoline compounds • D- Tubocurare • It 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 histamine • It causes maximum ganglion blockade. Because of ganglion blocking & histamine releasing property it can produce severe hypotension. • Due to histamine release it can produce severe bronchospasm.

15. Centrally acting muscle relaxants • These are drugs which produce muscle relaxation through central mechanism both at supraspinal & spinal level • Polysynaptic reflexes involved in maintenance of muscle tone are inhibited at both spinal & supraspinal level. It also produces sedation Uses • Muscle spasms. • Tetanus : IV diazepam is most effective. • Spastic neurological diseases like cerebral palsy,Spinal injuries. • Close reductions & dislocations in orthopedics.

16. 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 Action • It 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: • Neostigmine • Pyridostigmine • Edrophonium • Physostigmine

17. 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.

18. SIGNS OF ADEQUATE REVERSAL • Regular respiration with adequate tidal volume i.e. patient is able to maintain oxygen saturation on room air. • Spontaneous eye opening • Spontaneous limb movement • Able to protrude tongue • Upper airway reflexes returns like patient is able to cough & spit. • Able to lift head for more than 5 seconds. This is the best clinical sign.

19. CAUSES OF INADEQUATE REVERSAL • Inadequate dose of neostigmine. • Overdose of inhalational agents/opioids. • Renal Failure,Hepatic failure • Hypothermia • Electrolyte abnormalities (Hypokalemia, Hypocalcemia) • Associated neuromuscular diseases. • Shock • Acid Base abnormalities especially acidosis. It is impossible to reverse a patient with pCO2 more than 50mmHg.

20. Factors Prolonging the neuromuscular blocakde • Neonates • Old age • Obesity • Hepatic disease (both depolarizer & NMDR) • Renal disease ( only NDMR) • Inhalational agents : Prolong the block by both depolarizers & NDMR. Inhalational agents decrease the requirement of relaxant .The maximum relaxation is by ether followed by desflurane • Antibiotics: Both depolarizers & NMDR • Aminoglycosides. • Tetracyclines.

21. Local Anaesthetics : Except procaine local anaesthetics prolong the action by stabilizing post synaptic membrane. • Hypothermia : Decreases metabolism of muscle relaxants. • Hypocalcemia: Calcium is required for producing action potential. Action of NDMR is enhanced. • Hypokalemia : NMDR block is enhanced. • Acid base imbalances especially acidosis. • Calcium channel blockers • Dantrolene • Neuromuscular disease • Hypermagnesemia.

22. Drugs which antagonise Neuromuscular Blockade • They reverse the block by NDMR only • Phenytoin • Carbamazepine • Calcium • Cholinesterase inhibitors • Azathioprine • Steroids.