2. 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, Quinine II)Centrally acting o 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. R enal 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 DepolarizingNondepolarizing Also called Phase I block- Block preceded by muscle fasciculationsNo fasciculations Depolarizing blocking drugs are called Leptocurare Called pachycurare Does not require reversal rather cholinesterase inhibitors (Neostigmine) can prolong the depolarizing block ( because these agents also inhibit the pseudocholinesterase). Reversed by cholinesterase inhibitors like Neostigmine.

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.