Cholinergic Antagonist Lecture Notes PDF

Cholinergic Antagonist Learning outcomes Understand the basic pharmacology of major muscarinic antagonists - Pharmacokinetics, MOA, organ system effects Understand the therapeutic applications of major muscarinic antagonists and the most significant risks associated with their use. Choli...

Cholinergic Antagonist Learning outcomes Understand the basic pharmacology of major muscarinic antagonists - Pharmacokinetics, MOA, organ system effects Understand the therapeutic applications of major muscarinic antagonists and the most significant risks associated with their use. Cholinergic Antagonist Muscarinic Receptor Antagonist Muscarinic antagonist Recap !  Physiological Response to Muscarinic Blockade Tissue Response Eye Sphincter muscle (iris) Dilation- mydriasis Ciliary muscle Relaxation- distant vision Heart SA node Increase in HR Atria Increase in contractility AV node Increase in conduction + blicj Ventricle Increase in contractility Lung Bronchial smooth muscle Dilation Bronchial glands Decreased secretion Stomach Gastric smooth muscle Decreased motility & tone Sphincters Contraction Intestinal glands Decreased secretion  Physiological Response to Muscarinic Blockade Tissue Response Bladder Detrusor Relaxation Trigone & internal sphincter Contraction Adrenal medulla Decreased secretion NE & Epi Exocrine glands Pancreas Decreased secretion Salivary Decreased secretion Lacrimal Decreased secretion Pharyngeal Decreased secretion Sweat glands Decreased secretion Clinically Used Muscarinic Antagonist Atropine Hyoscine ( CT HAPI  ) Ipratropium Tiotropium Cyclopentolate Pirenzepine Atropine Atropine Natural alkaloid Tertiary amine relatively ______ soluble and cross BBB Competitively ________ binding of ACh to muscarinic receptors. Clinical uses: Sinus bradycardia As pre-anaesthetic medication (to dry secretion) Organophosphate poisoning Atropine Natural alkaloid Tertiary amine relatively ________ soluble and cross BBB Competitively _________ binding of ACh to muscarinic receptors. Clinical uses: Sinus bradycardia as pre-anaesthetic medication (to dry secretion) Organophosphate poisoning Sinus bradycardia Sinus Bradycardia treatment: Atropine MOA Atropine _________ the heart rate and improves the atrioventricular conduction by blocking the parasympathetic influences on the heart Atropine Natural alkaloid Tertiary amine relatively lipid soluble and cross BBB Competitively blocks binding of ACh to muscarinic receptors. Clinical uses: Sinus bradycardia as pre-anaesthetic medication (to dry secretion) Organophosphate poisoning Atropine Natural alkaloid Tertiary amine relatively lipid soluble and cross BBB Competitively blocks binding of ACh to muscarinic receptors. Clinical uses: Sinus bradycardia as pre-anaesthetic medication (to dry secretion) Organophosphate poisoning Side Effects of Atropine (Reactions unrelated to the therapeutic aim, occur at therapeutic doses) Scopolamine Scopolamine (Hyoscine) Competitive ___________ of ACh at muscarinic receptors Penetrate into the brain more readily compared to atropine Clinical uses: Prevention of nausea & vomiting in motion sickness Motion Sickness  Motion Sickness: Scopolamine MOA Blocks muscarinic receptors on vomiting centre (cut off vomiting impulse) Scopolamine butylbromide (Hyoscine butylbromide) Competitive antagonist of ACh at muscarinic receptors Poorly absorbed, _________CNS effects Clinical uses: Antispasmodic in IBS (hyoscine butylbromide) Antispasmodic: Scopolamine butylbromide MOA Ipratropium & Tiotropium Ipratropium, tiotropium Synthetic ___________ amine Short acting: ipratropium bromide Long acting: tiotropium bromide Clinical use: treatment of bronchospasm associated with asthma, chronic obstructive pulmonary disease, including chronic bronchitis and emphysema (administered via inhalation) Bronchoconstriction: Ipratropium & Tiotropium MOA Cyclopentolate Cyclopentolate Clinical use: To produce mydriasis and cycloplegia for diagnostic purposes Pirenzepine Pirenzepine M1 selective antagonist Clinical use: Peptic ulcer disease  Clinical Uses Clinical Use Muscarinic antagonist Neurological Prevention of motion sickness Hyoscine Parkinsonism, movement disorders caused Benzhexol, by APD Benztropine Opthalmic To dilate pupil Tropicamide, cyclopentolate Cardiovascular Treatment of sinus bradycardia Atropine Respiratory Asthma, COPD Ipratropium, Preanaesthetic med (to reduce salivary & tiotropium respiratory secretion) Atropine, glycopyrrolate Gastrointestinal Antispasmodic in IBS Hyoscine/ Peptic ulcer disease Dicycloverine Pirenzepine Organophosphorus Nerve agent/ insecticide poisoning Atropine poisoning Concept of Dominant Tone The dominant tone in an organ means that the branch of ANS (parasympathetic or sympathetic) innervating that organ dominant or more active. Drugs affecting the system which is dominant will have a more noticeable effect in that organ. E.g. gastrointestinal tract: dominant tone  parasympathetic system. IF cholinergic antagonist is given marked reduction in peristaltic activity & reduced GI tract secretion Thank you