MUSCLE RELAXANTS.pptx that's great slides gwe

Muscle relaxants

1. MUSCLE RELAXANTS Dr. NAJJUMA LAZIA

2. Introduction Inhalational agents (nitrous oxide, diethyl ether, cyclopropane and chloroform)were discovered before muscle relaxants. Surgical access for some procedures difficult Available options then were inhalational agents and local analgesia

3. Introduction Increased mortality and morbidity at initial discovery of muscle relaxants as demonstrated in a retrospective study by Beecher & Todd (1954). Later large doses were used and use of routine tracheal intubation and artificial ventilation then evolved.

4. Neuromuscular transmission. Acetylcholine is released from presynaptic nerve endings on passage of a nerve impulse down the axon to the nerve terminal. The junction cleft and post synaptic junction folds contains acetyl cholinesterase The nicotinic acetylcholine receptors on the postsynaptic membrane have five sub units

5. Feedback mechanism at the junction

6. Neuromuscular transmission Activation of the receptor allows movement of cations such as Na+, K+, Ca2+ and Mg2+ along their concentration gradients. When the end-plate potential reaches this critical threshold, it triggers an all-or-nothing action potential that passes around the sarcolemma to activate muscle contraction via a mechanism involving Ca2+ release from the sarcoplasmic reticulum.

7. Neuromuscular transmission In health, postsynaptic acetylcholine receptors are restricted to the neuromuscular junction. In many disease states affecting the neuromuscular junction, this control is lost and acetylcholine receptors of the fetal type develop on the adjacent muscle surface.

8. Pharmacology Neuromuscular blocking agents used regularly by anesthetists are classified into depolarizing (or noncompetitive) agents non-depolarizing (or competitive) agents

9. Structure of suxamethonium

10. Depolarizing muscle relaxants The only depolarizing relaxant now available in clinical practice is succinylcholine . It has the capacity to cling to each of the α units o f the postsynaptic acetylcholine receptor, altering its structural conformation and opening the ion channel, but for a longer period than does a molecule of acetylcholine.

11. Depolarizing muscle relaxants Administration of succinylcholine therefore results in an initial depolarization and muscle contraction, termed fasciculation . further action potentials cannot pass down the ion channels and the muscle becomes flaccid; repolarization does not occur.

12. Depolarizing muscle relaxants Dose 1 to 1.5mg/kg Onset of muscle relaxation; I minute Metabolised by plasma cholinesterase Recovery from neuromuscular block may start to occur within 3 min and is complete within 12–15 min. The use of neostigmine is contraindicated for reversing muscle blockade due to suxamethonium

13. Depolarizing muscle relaxants Uses Rapid sequence induction Difficult airway

14. Depolarizing muscle relaxants The exact structure of plasma cholinesterase is determined genetically by autosomal genes . A patient who is a heterozygote for the atypical gene demonstrates a longer effect from a standard dose of succinylcholine (about 30 min). If the individual is a homozygote for the atypical gene ,the duration of action of succinylcholine may exceed 2 h.

15. Depolarizing muscle relaxants The fluoride and silent have very little capacity to metabolize succinylcholine and thus neuromuscular block in the homozygous state can last for at least 3 h. How do manage such patients???

16. Other causes of prolonged blockade Pregnancy Liver disease Carcinomatosis and starvation Hypothyroidism Renal disease Cardiopulmonary bypass, plasmapheresis Anticholinesterases

17. Side effects of suxamethonium Muscle pains Increased intra-ocular pressure Increased intra-gastric pressure Hyperkalemia (renal failure , burns, neuromuscular disorders) Cardiovascular effects Anaphylactic reactions

18. Non depolarizing muscle relaxants . Unlike succinylcholine, these drugs do not alter the structural conformity of the postsynaptic acetylcholine receptor and therefore do not produce an initial contraction. Instead, they compete with the neurotransmitter How is recovery achieved?

19. Non depolarizing agents Benzylisoquinolinium compounds Tubocurarine Alcuronium Atracurium Mivacurium cisatracurium , Aminosteroid Pancuronium Vecuronium Pipecuronium Rocuronium

20. NDMBs A dose of at least 2 × ED95 is required to produce adequate conditions for reliable tracheal intubation in all patients.

21. Atracurium Dose Causes histamine release and may therefore produce a local wheal and flare around the injection site, especially if a small vein is used A metabolite of atracurium degradation, l audanosine has epileptogenic properties,

22. Rocuronium has a very rapid onset of action for a non-depolarizing muscle relaxant. The drug is excreted unchanged in the urine and in the bile, and thus the duration of action may be increased by severe renal or hepatic dysfunction.

23. Factors affecting the durationof blockade by NDMBs Suxamethonium Inhalational agents especially isoflurane, sevoflurane and enflurane PH changes Body temperature Age Electrolyte changes Myasthenia gravis

24. Reversal agents

25. Anticholinesterase These agents are used in clinical practice to inhibit the action of acetyl cholinesterase at the neuromuscular junction, thus prolonging the half-life of acetylcholine and potentiating its effect, especially in the presence of residual amounts of non-depolarizing muscle relaxant at the end of surgery.

26. Anticholinesterase The most commonly used anticholinesterase during anesthesia is neostigmine, but edrophonium and pyridostigmine are also available.

27. Neostigmine Neostigmine potentiates the action of acetylcholine wherever it is a neurotransmitter, including all cholinergic nerve endings. The usual dose of neostigmine is 0.035 mg kg–1, in combination with either atropine or Glycopyrrolate 0.01 mg kg–1. Neostigmine takes at least 2 min to have an initial effect, and recovery from neuromuscular block is maximally enhanced by 10 min.

28. Sugammedex A γ-cyclodextrin, was designed to chelate or encapsulate rocuronium (and to a lesser extent vecuronium) in the plasma, preventing its access to the nicotinic receptor and encouraging dissociation from it.