1. MUSCLE RELAXANTS

2. MORPHOLOGY :  NMJ is specialised on both nerve and muscle side to transmit & recieve chemical messages  each motor neuron runs from ventral horn of spinal cord/medulla to the NMJ as a large myelinated axon.  motor neuron repeatedly branches to contact many muscle cells & gather them in a functional group known as Motor Unit

3.  Junctional/synaptic cleft : the nerve is separated from muscle surface by a gap of approxmiately 50nm.  Basal lamina : these are the protein filaments that holds the nerve & muscle in a tight alignment that spnas the cleft between nerve & end plate  muscle surface is heavily corrugated with deep invaginations of the junctional cleft - primary & secondary cleft.

4. FORMATION OF NEUROTRANSMITTER AT MOTOR NERVE ENDINGS  axon of motor nerve carries electric signals from spinal cord to muscles  all the ion channels,enzymes,proteins,macromolecules, and membrane components needed by the nerve ending to synthesize,store & release Ach are made in cell body and transmitted to nerve ending by axonal trasnport  Ach is stored in the cytoplasm until it is trasnported into vesicles for release.

5. NERVE ACTION POTENTIAL

7. DRUG EFFECTS ON POSTJUNCTIONAL RECEPTORS NON DEPOLARISING MUSCLE RELAXANTS  all NDMRs impair or block neurotransmitter by competitively preventing the binding of Ach to the muscle AChR.  final outcome- block/transmission- depends on the relative concentrations of chemicals and their comparative affinities for receptor

8. REVERSAL  normally Acetylcholinesterase destroys Acetylcholine & removes it from a competition for a receptor. inhibitor of Acetylcholinesterase such as neostigmine blocks it -Ach conc rises high conc shifts the competition between Ach &NDMR in favor of the former,thereby improving the chance of two Ach molecules binding to a receptor causes reversal of NDMR effect.

9. SUCCINYLCHOLINE :  have affinity & submaximal intrinsic activity at N m receptor. acts on the receptors of the muscle,stimulates them and ultimately causes relaxation. it acts via 2 phases : phase 1: during this phase ( depolarising phase) they cause muscle fasciculations while they are depolarising muscle fibres phase 2 :after sufficient depolarisation has occured,phase 2(desensitisation phase) sets in and the muscle is no longer able to respond to Ach released by the nerve endings.

10. ROUTES AND DOSES :  I/V dose - 0.5-2mg/kg;onset of action : within 30seconds,duration of action 3- 5mins  intubation dose : 1-1.5mg/kg IV or 2.5-4mg/kg IM  ONSET : 60-90sec after IV adminstration and 2-3mins after IM dose  Duration : 4-6mins after IV DOSE & 10-30mins after IM dose  Hydrolysis : plasma pseudocholinesterase

11. EFFECTS :  CNS :  Raised intracranial pressure and raised intraocular pressure.  CVS : Because of cross-reactivity at the muscarinic acetylcholine receptors, Sch causes vagal cardiac dysrhythmias. Bradycardia, junctional rhythm and sinus arrest can occur particularly if a second dose is administered and particularly in Children.  RESPIRATORY : Occasionally leads to bronchospasm and excessive salivation due to muscarinic effects. Intragastric pressure is increased thereby theoretically increasing the risk of re gurgitation.

12. MISCELLANEOUS : Most of the other effects are secondary to the depolarization and subsequent contraction of skeletal muscle. Sch elevates serum potassium 0.3-0.5 mEq/L in normal patients. It can cause an exaggerated release Of potassium (leading to fatal hyperkalemia) in those With neuromuscular or muscle disease. Post-operative myalgia is Common particularly in young adults. Succinylcholine is a potent trigger of malignant hyperthermia

13.  CONTRAINDICATIONS : > Malignant Hýperthermia (MH) or presence of conditions associated with Pseudocholinesterase deficiency. > Deficiency can result as a genetic defect, as a consequence of various medications or a rescondition which would predispose to hyperkalemia after Sch-induced muscle contraction. Examples include recent paralysis (spinal cord injury or stroke), amyotrophic lateral sclerosis (ALS). Duchenne's muscular dystrophy and recent burn or crush injury. Myotonia ult of liver disease. > The latter two causes are usually relative while the genetic defect can produce a complete lack of pseudocholinesterase activity in homozygous individuals.The use of succinylcholine in a patient with pseudocholinestersase deficiency leads to prolonged paralysis. >Hyperkalemia >Presence of neurologic or muscular congenita or myotonia dystrophica can manifest sustained contraction with Sch.

14. ATRACURIUM :  Class : Nondepolarizing skeletal muscle relaxant (NDMR),: short-acting.  Uses: Atracurium is used to facilitate intubation and controlled ventilation action.  Main action : Competitive, non-depolarizing neuromuscular blockade.  Main action : Atracurium acts by competitive antagonism of acetylchOIine at nicotinic (n2) receptors in the post-synaptic membrane Of the neuromuscular junction.

15. The drug is administered intravenously. The ED95 of atracurium is estimated to be 0.23 mg/kg. An initial dose of 0.3-0.6 mg/kg is recommended, providing muscle relaxation for between 15 and 35 minutes Maintenance Of neuromuscular blockade may be achieved With bolus doses Of 0.1-0.2 mg/kg.

16. Effects : <> Musculoskeletal : The neuromuscular blockade effects of non-depolarizing muscle relaxants are potentiated by succinylcholine, volatile anesthetics. aminoglycosides, lithium, loop diureties, lidocaine, magnesiurm, lithium, ganglionic blockers hypothermia, hypokalemia and respiratory acidosis. Enhanced neuromuscular blockade is seen in patients with myasthenia gravis or myopathies The effects of ndmr are antagonized by cholinesterase inhibitors. Increased resistance to ndmr is seen inpatients on theophylline, burn patients and those with paresis or paralysis. Histamine release may occur with rapid administration or higher dosages produces an excitatory metabolite called laudanosine Muscle relaxants are the most common cause of anaphylactoid reactions under general anesthesia.

17. CIS -ATRACURIUM : CLASS : Non-depolarizing skeletal muscle relaxant (NDMR); intermediate-acting. ACTION : Competitive, non-depolarizing neuromuscular blockade. Mode of action: Cisatracurium acts by competitive antagonism of acetylcholine at nicotinic (N2) receptors at the post-synaptic membrane of the neuromuscular junction. An initial doge of 0.15 mg/kg is recommended, providing good to excellent intubating conditions in 120 seconds.

18. VECURONIUM Main action Competitive non-depolarizing neuromuscular blockade. Mode of action Vecuroniurn acts by competitive antagonism Of acetylcholine at nicotinic (N2) receptors at the post-synaptic membrane of the neuromuscular junction. drug also have some pre-junctional action, An initial dose of 0.08-0.1 mg/kg is recommended, providing muscle relaxation for between 25 and 40 minutes, Maintenance of neuromuscular blockade may be achieved with bolus doses of 0.02- 0.03 mg/kg. Vecuroniurn may be administered by intravenous infusion at a rate of 0.8-1.4 micrograms/kg/min. non-cumulative with repeated administration

19. Effects CVS : Vecuronium hasminimal cardiovascular effects; with large doses, a slight (9%) increase in the cardiac output and 12% decrease in the systemic vascular resistance may occur. Unlike pancuronium, the drug will not antagonize the haemodynamic changes or known side effects produced by other pharmaceutical agents or surgical factors. RESPIRATORY : Neuromuscular blockade leads to apnoea.Vecuroniurn has a very low potential for histamine release; bronchospasm is extremely uncommon. CNS : has no effect on intracranial or intraocular pressure

20. ROCURONIUM Class Non-depolarizing muscle relaxant (NDMR); shortacting Main action Competitive neuromuscular blockade Mode of action Rocuronium acts by competitive antagonism of acetylcholine at nicotinic (N2) receptors at the post-synaptic membrane of the neuromuscular junction;

21. Rocuroniurn is administered intravenously; The normal intubating dose is 0.6 mg/kg, with subsequent doses ot 0.15mg/kg This intubating dose equates to twice the ed90 for rocuronium (ed90 0.3 mg/kg) and results in excellent intubating conditions in 80% of cases within 60 seconds. A dose of 1 mg/kg is recommended when rocuronium is used during modified rapid sequence induction, resulting in intubating conditions within 60 seconds approx.

22. Dose Intubation: 0.45-.9 mg/kg Maintenance bolus 0.1-0.2 mg/kg Onset Dose-dependent: 1-1-5 minutes (0.6 mg/kg) 0.5-1.0 minutes (0.9 mg/kg) Higher dose is therefore suitable for rapid sequence induction. Duration Dose-dependent: 31 minutes (0.6 mg/kg), 90 minutes (0.9 mg/kg) Elimination Hepato-biliary (70%); renal (10%)

23. Effects CVS Very weak vagolytic effect. Musculoskeletal The neuromuscular blockade effects of non-depolarizing muscle relaxants are potentiated by succinylcholine, volatile anesthetics, aminoglycosides, lithium, loop diuretics, lidocaine, magnesium, lithium, ganglionic blockers, hypothermia, hypckalemia and respiratory acidosis. Enhanced neuromuscular blockade is seen in patients with myasthenia gravis or myopathies. The effects of NDMR are antagonized by cholinesterase inhibitors. Increased resistance to ÑDMRS is seen in patients On theophylline, burn patients and those with paresis or paralysis. Muscle relaxants are the most common cause of anaphylactoid reactions under general anesthesia.

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