Myasthenia Gravis disease pharmacology ppt.pptx

Myasthenia Gravis disease pharmacology

1. Myasthenia Gravis Presented By: Paradhe Ayodhya Tanaji Guided By : Dr. Mandade Sir M Pharm 1 st Year (Pharmacology) (Pharmacology Department) Sudhakar Rao Naik Institute Of Pharmacy Pusad

2. Content M yasthenia gravis I ntroduction E tiology of MG D rug used in M G

3. Myasthenia Gravis M yasthenia gravis which is a L atin or G reek in origin means grave or serious muscle weakness M yasthenia gravis is an autoimmune disorder affecting the myoneural junction characterized by fluctuating in neuromuscular or voluntary muscle weakness and fatigability not a brain disorder-brain function normally I t is an autoimmune disorder in which weakness is cause by circulating antibodies that block the acetylcholine receptor mainly nicotinic neuromuscular receptor at the postsynaptic nm junction inhibiting the excitatory neurotransmitter acetylcholine throughout nm junction

4. Sign and symptoms Chewing problem, limited facial expressions, Facial paralysis, difficulty in breathing, difficulty in walking

5. Anatomy of neuromuscular junction components P resynaptic nerve S ynaptic cleft P ostsynaptic nerve NMJ is specialized synapse between neuron and muscle I t allows signals from the nervous system to contact muscle fibers causing them to contract A cetylcholine plays an important role in neurotransmission acetylcholine vesicles present in presynaptic nerve once a motor nerve action potential reaches to the presynaptic nerve terminal it cause increase in the intracellular calcium concentration

6. T his increase in calcium concentration allows the acetylcholine vesicles to fuse with plasma membrane at the presynaptic membrane and thus releasing acetylcholine into the synapse. Acetylcholine present in synapse it is able to bind nicotinic acetylcholine receptor, increasing conductance of certain cations sod. and pot. in the postsynaptic membrane and producing an excitatory effect. Diagnosis- Edrophonium is used for diagnosis of myasthenia gravis Edrophonium MG cholinergic crisis patients feels better after patients conditions worsen after getting edrophonium edrophonium

7. Etiology of Mg In mg antibodies are directed towards the acetylcholine receptor at the NMJ of skeletal muscle result in: 1. Destruction of all one third of nicotinic NMJ receptor in skeletal muscle 2. Flattening of postsynaptic folds 3. Widening of synaptic cleft acetylcholine is an important neurotransmitter that stimulates muscle contraction

8. E tiology of MG Normal Neuromuscular Transmission Neuromuscular Transmission In Myasthenia Gravis Motor Nerve Impulse Travel To Motor Nerve Terminal Acetylcholine Is Released . Acetylcholine Defuse Across Synapse In MG Acetylcholine Receptor Site In Motor Acetylcholine Receptor Site Weakened Or Destroy By The End Plates Depolarized Muscle Fibers Attachment Of Antibodies On Nm Receptors And Block Them Depolarization Spreads And Causing Depolarization And Muscle Contraction Does Not Occurs, Muscle Contraction Neuromuscular Transmission Is Blocked.

9. Treatment for MG Classification 1.ACHE inhibitors N eostigmine, P yridostigmine 2. Immunosuppressant’s A zathioprine, Cyclosporine 3. T hymectomy- removal of thymus gland which is part of immune system, may reduce mg symptoms 4. P lasmapheresis- nothing but plasma exchange this process remove harmful antibodies from blood which may result improvement in muscle strength 5. Combination of medicine Steroids addition with immunosuppressant 6. Others A minoglycoside antibiotics, P henytoin, C hloroquine

10. Pharmacology Of Neostigmine N eostigmine is choline esterase inhibitors, polar compound (water soluble) mechanism of action Neostigmine inhibit the hydrolysis of acetylcholine by binding with the enzyme acetylcholine choline esterase at the site of cholinergic transmission by reducing the hydrolysis of acetylcholine the transmission of nerve impulses increases to the muscles fibers and muscle get contaminated

11. Pharmacokinetics 1. absorption- poorly absorbed orally mainly given by IM, IV, SC onset of action 10-20 min ( inj.) bioavailability is 115% 2. distribution- bound to human serum albumin 15-25% not distributed in cornea and BBB 3. metabolism- slowly hydrolysis by acetylcholine esterase and also plasma esterase mainly metabolized in liver 4. excretion- unchanged form 70% and alcoholic metabolites 30% excreted in urine

12. Uses M ainly used in MG N eostigmine inj. prevent or treat certain kidney or intestinal problems G iven after surgery to help the reverse effect of certain type of medicines that have been used to muscle relax Adverse Effects M uscarinic- nausea, vomiting, dizziness, abdominal cramps, increase salivation, increase bronchial secretion, bradycardia, acidity, bronchoconstriction so atropine given with neostigmine because atropine block M1, M2, M3 receptors N icotinic- muscle cramps, weakness, Contraindication renal failure, peritonitis condition hypersensitivity reaction, epilepsy, bradycardia, bronchial asthma, peptic ulcer

13. References 1 . Essential of medical pharmacology 8 th edition KD Tripathi 2. H arrison’s neurology in clinical medicine, 3 rd edition myasthenia gravis and other diseases of the neuromuscular junctiondaniel b. drachman 3. L aura dresser et al myasthenia gravis: Epidemiology, P athophysiology And Clinical Manifestation

14. Thank you