Autonomic Nervous System Drugs PDF

4. ANS 1 Autonomic Nervous Syst...

4. ANS 1 Autonomic Nervous System Drugs: Introduction and Parasympathomimetics produces actions similar to Definition acetylcholine (ACh) or mimic the actions of ACh act on ACh receptor stimulants 1. Cholinergic drugs / Cholinomimetic Directly-acting directly binds and activate the drugs / Parasympathomimetics muscarinic and nicotinic receptors Types & produce the effects act on cholinesterase inhibitors Indirectly-acting increase local concentration of act by binding with the enzyme ACh Therapeutically not using stimulates both M & N receptors - Acetylcholine Diffuse action (nonselective action) produce more adverse effects Choline esters very short duration of action (few Rapidly hydrolyzed by AChEs seconds) Bethanichol stimulates only muscarinic Features receptors Directly acting severe salivations. ADRs sweating decreases intraocular pressure Alkaloid Pilocarpine (IOP) – by miosis Therapeutic uses increases drainage of aqueous humor Mitotics - rapidly reduces IOP Treatment of glaucoma Clinical uses Sj gren's syndrome Xerostomia Physostigmine Neostigmine Pyridostigmine Reversible (Carbamates) Edrophonium 2. Classifications of Cholinergic drugs Indirectly acting: Echothiophate Anticholinesterases (AntiChEs) Example Drugs Malathion Diazinon therapeutically not useful important as poisonous substances Irreversible (Organophosphates) Therapeutic values used as insecticides in agriculture elds commonly used as suicidal & homicidal poison MoA G-protein coupled receptor Muscarinic receptors (M) 3. Cholinergic receptors Ion-channel linked receptor Nicotinic receptors (N) Contraction of circular muscle of Miosis iris 1. Eyes Accommodation for near vision vision fixed for near objects (cyclospasm) reduces intraocular pressure esp. in glaucomatous patients ↑ GI motility & secretions 2. Smooth muscle - contracted Bronchospasm- Constriction of bronchial smooth muscles Respiratory tract (M3 receptors) Increases the tracheobronchial mucus secretions 1. Pharmacological actions contraction of detrusor muscle 3. Urinary bladder Facilitate the micturition (muscarinic) of ACh; relaxation of trigone & sphincter ↓PVR (pulmonary vascular resistance), 4. CVS ↓HR ↓Force of Contraction (atria) 5. Blood vessels (M3 receptors) Vasodilatation - ↓ BP Sweat (thermoregulatory) 6. Glands increased secretion Saliva from salivary glands Tears from lacrimal gland Sympathetic stimulation increase HR & BP Cholinergic drugs – direct acting Autonomic ganglia (NN) decrease HR & BP 4. Therapeutic value of ACh Parasympathetic stimulation increase GIT motility & secretion 2. Pharmacological actions increase frequency of micturition (nicotinic) of ACh Secretion epinephrine and Adrenal medulla (NN) norepinephrine Skeletal muscle (NM) Contraction (twitching) Sweating salivation decrease HR & BP Nausea 3. Adverse effects Bronchospasm Flushing abdominal pain diarrhea inhibit the breakdown of acetylcholine widely utilized as pesticides Acetylcholinesterase inhibitors or misused, produce toxic responses Cholinergic drugs – indirect acting Anticholinesterases in mammals and man MoA Refer to Excessive muscarinic and nicotinic stimulations Diarrhea, vomiting Urination Miosis, pin point pupil Bradycardia Muscarinic effects. ( DUMBBELSS ) Bronchoconstriction Excitation (CNS and muscle) Lacrimation Salivation 5. Toxicity of AChE inhibitors/ Sweating Organophosphorus Poisoning depolarizing neuromuscular blockade, excitation followed by Skeletal muscle depolarizing paralysis 去极化神经肌 阻滞，兴奋后去极化瘫 Nicotinic effects 痪 convulsions CNS stimulation coma Maintenance of respiration antidote for overdose of Management Toxicity of AChE All muscarinic effects are blocked cholinergic drugs, IV inject in large inhibitors by atropine doses Reactivation of AChE with initiated as soon as possible, prior Pralidoxime (PAM) to beginning of aging Pilocarpine 1. Open / Wide angle glaucoma Physostigmine Neostigmine 2. Myasthenia gravis Pyridostigmine Neostigmine 6. Overall Uses of Cholinergic Drugs 3. Post-operative urinary retention Pyridostigmine Bethanechol Neostigmine 4. Post operative parlytic ileus / Pyridostigmine congenital megacolon Bethanechol 5. Drug poisoning Atropine : Physostigmine a chronic autoimmune disorder antibodies destroy the Introduction communication between nerves and muscle resulting in weakness of the skeletal muscles affects the voluntary muscles of especially those that control the Affected the body, eyes, mouth, throat and limbs. strike anyone at any age Who more frequently seen in - young women (age 20 and 30) - men aged 50 and older unknown no cure Causes early detection and prompt medical management can help people live longer, more functional lives Drooping of one or both eyelids (ptosis) 7. Myasthenia gravis Double vision (diplopia) Altered speaking Difficulty swallowing Symptoms Problems chewing Limited facial expressions rising from sitting to standing climbing stairs Waddling gait, head drop and dif culty performing physical tasks brushing teeth (repetitive action) such as lifting washing hair physical activity often leads to tiredness Acetylcholinesterase inhibitors (pyridostigmine) Immunosuppressants Treatments (azathioprine) In selected cases Thymectomy surgical removal of the thymus gland fi ö fi 肉