SKELETAL MUSCLE RELAXENT.pptx

drugs used as skeletal muscle relaxant

1. PHARMACOLOGY-1 SKELETAL MUSCLE RELAXANT UNIT-3

2. INTRODUCTION; The drugs which are used to treat skeletal muscle spasticity( a motor disorder characterized by rapid and involuntary muscle contraction results in muscle stiffness and difficulties in speech and movement. ) are called as skeletal muscle relaxant . These can produce their action either by acting on central nervous system or by acting at peripheral nervous system. These drugs are commonly used with general anaesthetics to produce muscle relaxation on surgical procedures and also for increase the action of general anaesthetic.

3. CLASSIFICATION;

4. PERIPHERALLY ACTING MUSCLE RELAXANT; Peripherally acting drugs are exert their action either by directly acting on muscle fibers or by act at NeuroMuscular junction (NMJ).Based on this factor peripheral muscle relaxant is further divided into * Neuromuscular blocking agent *Directly acting agents ADVANTAGES; » They Improve the quality of life »They do not cause unconsciousness »They exhibit synergistic action with general anaesthetic DISADVANTAGES: » They are not effective for all kind of pain » They cause loss of voluntary power »No antagonist is available to antagonize the action of depolarizing muscle relaxant.

5. Neuromuscular blocking agents ;(NMBA’s) Neuromuscular blocking agents are the peripherally acting skeletal muscle relaxant they reduce the spasticity without affecting the consciousness and normal voluntary movements. They generally block the neuromuscular transmission by acting presynaptically through inhibition of acetylcholine synthesis or release or by acting postsynaptically at Non receptor. As this result the development of muscle action potential required for Muscular contraction is inhibited. Based on mechanism of blocking the impulse transmission at the neuromuscular junction, The neuromuscular blocking agents are classified into Depolarizing blocking agents Non depolarizing blocking agents

6. DEPOLARIZING BLOCKING AGENT; GENERAL MECHANISM Depolarizing blockers act by binding to Nicotinic receptors (Nm) on the motor end plate and causes the opening of sodium channels(Na++) this leads to depolarization further contact of drug with receptor leads to desensitization of the receptor which caused the paralysis of the muscle. The mechanism of depolarising blocking agents is occurs by two phases namely depolarization phase and desensitizing phase. DEPOLARISATION PHASE; Drug bind to the nicotinic receptor (Nm) and causes the opening of ion channels causes entry of sodium ions.This is causes the persistent depolarization so that it is called as Depolarisation phase. DESENSITIZING PHASE: Continuous exposure of drug to the nicotinic receptor causes the desensitization of receptor which is unresponsive to the acetyl choline (Ach) which is results in the paralysis or relaxation of skeletal muscle

7. PHARMACODYNAMICS; 1. On Skeletal system; A single IV dose of succinylcholine (Sch) produce transistant muscular fasciculations followed by muscle paralysis . 2. On Cardiovascular system; On repeated administration of Succinylcholine initially causes bradycardia and then causes tachycardia due to its action with muscarinic receptor 3. On Respiratory system; Due to the contraction of the internal and external intercostal muscles respiratory depression is occurs. 4. On Eye; Due to the contraction extraocular muscle results in the increased intraocular pressure (IOP) causes the eye pain. 5. On Autonomic ganglia ; Sch stimulates the ganglia because of its agonistic action on Nicotinic receptor(Nn)

8. PHARMACOKINETICS; As these drugs process quaternary ammonium groups in their molecule they are not absorbed completely when taken orally.therefore these drugs are administered by intravenous route. They do not cross the blood-brain barrier and placental barrier drugs like succinylcholine get rapidly hydrolysed by plasma pseudocholinesterase to succinylmonocholine and then to succinic acid and Choline. Succinylcholine was rapidly hydrolysed by pseudocholinesterase therefore the duration of action of the drug is in the range of 3 to 10 minutes but in people having liver diseases or deficiency of this enzymes having prolonged duration of action this is refers as succinylcholine apnoea There is no antidote is available therefore, fresh frozen plasma is infused into the patient Patient should be ventilated artificially until full recovery Anaesthesia should be continued until full recovery

9. ADVERSE EFFECTS; Muscle pain is due to initial fasciculations (muscle soreness). Increased IOP due to contraction of external ocular muscle and its last for few minute . Aspiration of gastric contents may occur due to increased intragastric pressure. Hyperkalemia due to fasciculations release potassium(k+) into the blood . Sinus bradycardia is due to vagus stimulation succinylcholine apni prolonged apnea. CONTRAINDICATIONS; Contraindicated in case of hypokalemia, glaucoma and Myasthenia gravis.special precautions are to be taken during severe burns, hepatic and renal failure pregnancy lactation and in Pediatrics.

10. DRUGS; Succinylcholine; It is also called suxamethonium chloride. succinylcholine is hygroscopic compound consisting to molecules of acetylcholine which are further linked by acetyl group. Decamethonium; It was the first synthesized neuromuscular blocking agent. neuromuscular blockade is due to 10 to 12 unsubstituted methylene group. Its onset of action is slow when compared to the suxamethonium .It is excreted in urine as unchanged drug .

11. NON-DEPOLARISING BLOCKING AGENT; Nondepolarizing blocking agents acticet competitive antagonist again acetylcholine Postsynaptic acetylcholine receptor site they are also known as competitive neuromuscular blockers. GENERAL MECHANISM; Non depolarising muscle relaxant bind to the nicotinic receptor(NM) Competitively against acetylcholine result in the inhibition of sodium Channels and Excitatory postsynaptic potential. These drug block the NM receptor thus prevent the binding of acetylcholine . Because of this the frequency of opening of sodium channel is reduced and the end plate potential is not generated in the absence of plate potential the motor nerve impulse is fail to induce the contraction in the skeletal muscle and thus the skeletal muscle relaxation is induced. This agent prevents the depolarization caused by acetylation so that these are called as non depolarizing blocking agent.

12. PHARMACODYNAMICS; On GIT ; Non depolarizing blocking drugs reduce the tone and motility of the GIT due to the ganglionic blockade. On Respiratory system; They may cause bronchospasm by releasing histamine from the mast cell. On central nervous system ;As these drugs cannot penetrate the blood-brain barrier therefore they do not produce any CNS effect. On skeletal muscles; competitive blockers upon intravenous administration produce muscle weakness followed by flaccid paralysis . On cardiovascular system; Competitive blockers produce significant decrease in the blood pressure mainly by releasing histamine and partially by blocking autonomic ganglia and reduce the the venous return. Other nondepolarizing Drugs produce insignificant effect on blood pressure and heart rate.

13. PHARMACOKINETICS; Nondepolarizing blockers are not well absorbed when taken orally hence their intravenous administration is recommended. Their penetration capacity through the lipoidal membrane is very poor so that they does not cross the blood-brain barrier and placental barrier. In neuromuscular blocking agents there is a correlation between the elimination and duration of action. For examples; Drugs eliminated by Kidneys like d-TC & pancuronium have longer duration of action. Drugs eliminated by liver like vecuronium atracurium have intermediate duration of action . Drugs eliminated by plasma like my back curium have shorter duration of action.

14. ADVERSE EFFECTS; Respiratory paralysis and hypoxia; The major drawback of the nondepolarizing blockers is respiratory paralysis and hypoxia this can be treated by giving neostigmine and artificial . Hypotension; Hypotension is commonly seen in hypovolemic patients and can be treated by giving IV fluids. Asthma; Drugs like d-TC and Histamine releasing drugs induce asthma this can be counteracted by giving antihistamines. Tachycardia ; Pancuronium vecuronium and gallamine cause tachycardia tachycardia due to their vagal ganglion blockade effect. Miscellaneous; They cause paralysis of oesophageal sphincter and diaphragm due to which gastric juice returns into the oesophagus.

15. LA-NDB IN’A-NDB IN’A-NDB SA-NDB

16. DIRECTLY ACTING AGENTS; DANTROLENE; Dantrolene is an analogue of Phenytoin whose site of action lies outside the central nervous system. MECHANISM OF ACTION; Dantrolene interferes with the release of Calcium from its stores in skeletal muscles( sarcoplasmic reticulum ). It inhibit the excitation-contraction coupling in the muscle fibre . Calcium is released from the sarcoplasmic reticulum via Calcium channel called the ryanodine receptor (RyR) channel and dantrolene blocks the opening of this channel results in the the relaxation of skeletal muscle.

17. Pharmacokinetics; It is a poorly absorbed by the GIT through the oral route. its half life is about 9 to 12 hours. It is mainly metabolized in the liver and excreted in the bile and urine. Adverse effects ; Diarrhoea, Sedation, Muscular weakness, Hepatotoxicity. Therapeutic Uses; Dantrolene is used to treat spastic disorder resulting from spinal cord injury and multiple sclerosis. This Drug of choice for the treatment of malignant hyperthermia caused by Succinylcholine. It is also used in the treatment of neuroleptic malignant syndrome.

18. A Seminar by; Venkatesan.B;- 2 Year BPHARM