Skeletal muscle relaxants drugs 0001.pptx assignment.pptx

Study hard

1. PHARMACOLOGY ASSIGNMENT Skeletal Muscle Relaxants

2. Drug List Neuromuscular Blockers Spasmolytic Drugs Central Peripheral Non- depolarizing Blockers Tubocurarine Mivacurium Cisatracurium Depolarizing Blockers Succinylcholine Baclofen Tizanidine Gabapentin Benzodiazepines Dantrolene Botulinum Toxin * More drugs are mentioned in other slides

3. 1. P resynaptic term i nal 2. S arcolemma 3. Synaptic vesicles 4. Acetylcholine receptors 5. Mitochondrion

4. Muscle Relaxants What are they used for? Facilitate intubation of the trachea Facilitate mechanical ventilation Optimized surgical working conditions Treatment of Convulsions/ seizures

5. Also used for Muscle spasticity Muscle Spasms What are spasticity and spasms? Spasticity can be described as involuntary muscle stiffness and spasms as involuntary muscle contractions. Any muscle can be affected but spasticity and spasms tend to predominantly affect a person's limbs or trunk.

6. Muscle Spasticity The Adducted/Internally Rotated Shoulder The Flexed Wrist T h e Pronated Forearm The Cllnched Fist The Flexed Elbow The T humb -in- Pa l m Deform i ty Eq u inovaru s Striatal Toe Stiff Knee

7. Definition of muscle spasm Increased muscle tone together with muscle weakness It is often associated with cerebral palsy, multiple sclerosis, and stroke.

8. Causes of Muscle Spasms Seen after musculoskeletal injury and inflammation Involve afferent nociceptive input from damaged area Excitation of alpha motor outflow Tonic contraction of affected muscle Build up of pain- mediating metabolites

9. Levels of Muscle Relaxant Intervention Spinal Cord NEUROMUSCULAR Junction Muscle Cells

10. Muscle Relaxants Definition: Drugs which relax skeletal muscles by acting at the neuromuscular junction Depolarizing muscle relaxant Succinylcholine Nondepolarizing muscle relaxants Short acting Intermediate acting Long acting

11. They can also be called Antagonist {nondepolarizing) neuromuscular blocking drugs prevent access of acetylcholine to its NM receptor and prevent depolarization of the motor end plate (d- tubocurarine) Agonist {depolarizing) neuromuscular blocking drugs produce excessive depolarization of the motor end plate by causing excessive stimulation of the NM receptor (Succinylcholine)

12. Drug List

13. Drug List Neuromuscular Blockers Spasmolytic Drugs Central Peripheral Non- depolarizing Blockers Tubocurarine Mivacurium Cisatracurium Depolarizing Blockers Succinylcholine Baclofen Tizanidine Gabapentin Benzodiazepines Dantrolene Botulinum Toxin * More drugs are mentioned in other slides

14. Succinylcholine What is the mechanism of action ? Physically resemble Ach Act as acetylcholine receptor agonist Not metabolized locally at NMJ Metabolized by pseudocholinesterase in plasma Depolarizing action persists > Ach Continuous end- plate depolarization causes muscle relaxation Neuromuscular blockers

15. Succinylcholine Wvtett Ls tvte cLLV\- LcetL use of succLV\- rjLcvtoLLV\- e? Most often used to facilitate intubation Onset 30- 60 seconds, duration 5- 10 minutes

16. Succinylcholine What is phase I neuromuscular blockade? Repetitive firing and release of neurotransmitter. Acetylcholine receptors remain open. Preceded by fasciculations. What is phase II neuromuscular blockade? Postjunctional membrane does not respond to ACh even when resting membrane potential is restored i.e. Desensitisation blockade or Phase 11 block.

17. Succinylcholine Does tt l1ave stc;{e effects? Cardiovascular Fasciculation Muscle pain Increase intraocular pressure Increase intragastric pressure Increase intracranial pressure Hyperkalemia Malignant hyperthermia

18. Nondepolarizing Muscle Relaxants Long acting Pancuronium Intermediate acting Atracurium Vecuronium Rocuronium Cisatracurium Short acting Mivacurium Mechanism of Action All bind nicotinic Ach receptors and competitively block Acetylcholine, thereby preventing muscle contraction i.e. They are competitive antagonists

19. Tubocurarine This was the first muscle relaxant used clinically Therapeutic Use: Adjuvant drugs in surgical anesthesia Pharmacology: Must be given by injection because they are poorly absorbed orally. Do not cross the BBB. Elimination: Generally excreted unchanged (i.e. not metabolized). Adverse Effects: Tubocurarine causes release of histamine from mast cells - decrease in blood pressure, bronchospasms, skin wheals. Drug interaction: Competes with succinylcholine for it's the end plate depolarizing effect.

20. Pancuronium It is an Aminosteroid compound Onset 3- 5 minutes, duration 60-90 minutes liver (15%) Elimination mainly by kidney (85%), Side effects : hypertension, tachycrdia, dysrhythmia,

21. Vecuronium Analogue of pancuronium Much less vagolytic effect and shorter duration than pancuronium Onset 3- 5 minutes duration 20-35 minutes Elimination 40% by kidney, 60% by liver

22. Rocuronium Analogue of vecuronium Rapid onset 1- 2 minutes, duration 20- 35 minutes Onset of action similar to that of succinylcholine Intubating dose 0.6 mg/kg Elimination primarily by liver, slightly by kidney

23. Atracurium Metabolized by Ester hydrolysis Hofmann elimination (spontaneous degradation in plasma and tissue at normal body pH and temperature) Onset 3- 5 minutes, duration 25-35 minutes Side effects: histamine release causing hypotension, tachycardia, bronchospasm Laudanosine toxicity (Laudanosine is a metabolite of atracurium and cisatracurium. It decreases seizure threshold and this it can induce seizures, however 1 such concentrations are unlikely to be produced at therapeudc doses)

24. Cisatracurium Isomer of atracurium Metabolized by Hofmann elimination Onset 3-5 minutes, duration 20- 35 minutes Minimal cardiovascular side effects Much less laudanosine produced

25. Mivacurium Has the shortest duration of action of all nondepolarizing muscle relaxants Onset of action is significantly slower Use of a larger dose to speed the onset can be associated with profound histamine release leading to hypotension, flushing, and bronchospasm. Clearance of mivacurium by plasma cholinesterase is rapid and independent of the liver or kidney. Mivacurium is no longer in widespread clinical use. It is an investigational ultra- short- acting

26. Drug Interactions Cholinesterase Inhibitors decrease the effectiveness of nondepolarizing agents • Aminoglycoside antibiotics increase action of nondepolarizing drugs Calcium channel blockers increase the actions of nondepolarizing drugs Inhalational anesthetics enhance neuromuscular blockade by nondepolarizing drugs

27. Reversal of Neuromuscular Blockade Why do we need to reverse the effect of neuromuscular blockers? Because they paralyze the muscles. Once the surgery is over, the muscles need to work again. Goal: re-establishment of spontaneous respiration and the ability to protect airway from aspiration

28. Reversal of Neuromuscular Blockade by Anticholinesterases Effectiveness of anticholinesterases depends on the degree of recovery present when they are administered Anticholinesterases Neostigmine Onset 3-5 minutes, elimination halflife 77 minutes Pyridostigmine Edrophonium

29. Inhibiting activity of acetylcholineesterase More Ach available at NMJ, compete for sites on nicotinic cholinergic receptors Action at muscarinic cholinergic receptor Bradycardia Hypersecretion Increased intestinal tone

30. What do we do about side effects? Muscarinic side effects are minimized by anticholinergic agents Atropine Dose 0.01-0.02 mg/kg Scopolamine glycopyrrolate

31. Drug List Neuromuscular Blockers Spasmolytic Drugs Central Peripheral Non- depolarizing Blockers Tubocurarine Mivacurium Cisatracurium Depolarizing Blockers Succinylcholine Baclofen Tizanidine Gabapentin Benzodiazepines Dantrolene Botulinum Toxin * More drugs are mentioned in other slides

32. Centrally acting spasmolytic drugs Drug Baclophen Tizanidine Gabapentin Diazepam Mechanism GABA 6 receptors causing hyperpolarization by increasing potassium conductance Averse effects: drowsiness and increased seizure activity a2 adrenoreceptor agonist Unknown but may enhance GABA synthesis GABAA receptor

33. Baclofen Mechanism of action: GABA 8 agonist Clinical effects: decreased hyperreflexia; reduced painful spasms; reduced anxiety

34. Baclofen Adverse effects: weakness, sedation, hypotonia, ataxia, confusion, fatigue, nausea, liver toxicity Chronic effects: rapid withdrawal may cause seizures, confusion, increased spasticity Route of administration: oral, intrathecal

35. Tizanidine and Clonidine Mechanism of action: alpha-2 receptor agonist Clinical effects: reduced tone, spasm frequency, and hyperreflexia

36. Tizanidine and Clonidine Adverse effects: drowsiness, dizziness, dry mouth, orthostatic hypotension Chronic effects: rebound hypertension with rapid withdrawal Route of administration: oral, transdermal patch (Clonidine)

37. Benzodiazepines Diazepam Lorazepam (Ativan) Clonazepam Clorazepate Ketazolam Tetrazepam

38. Diazepam (Valium) Mechanism of action: enhance GABAA activity (chloride channels) Clinical effects: decreased resistance to passive joint range of motion (ROM) ; decreased hyperreflexia; reduced painful spasms; sedation; reduced anxiety

39. Diazepam (Valium) Adverse effects: sedation, weakness, hypotension, memory impairment, ataxia, confusion, depression Chronic effects: dependency, withdrawal, and tolerance possible Routes of administration: oral, intravenous, rectal

40. Peripheraly acting spasmolytic drugs Dantrolene Mechanism of action: Dantrolene reduces skeletal muscle strength by interfering with excitation-contraction coupling in the muscle fibers Normal contraction involves release of calcium from its stores in the sarcoplasmic reticulum through a calcium channel Dantrolene interferes with the release of calcium through this sarcoplasmic reticulum calcium channel.

41. Dantrolene: Indications: Muscle spasticity Malignant hyperthermia:

42. Botulinum Toxin (Botox) Enters the pre-synaptic terminal and binds to acetylcholine Inhibits acetlycholine from entering the synaptic cleft Toxin serves as a block at the neuromuscular unction Can be administered to a specific muscle or group via local injection

43. Botox Used in treatment of patients with focal dystonia as found in stroke and spinal cord lesions Used to restore volitional motor control thus increasing use of extremities and improving function, mobility and opportunities to participate in meaningful occupations Prevention of joint contraction and fixation

44. I hank¥OU