Pharmacology of ANS: Anticholinergics PDF

Pharmacology of ANS Anticholinergics Dr. Rajasekhar Chinta Associate Professor of Pharmacology MUCM, Level 09-ACB-01 Learning outcomes Classification of antimuscarinic drugs Pharmacological actions of atropine Therapeutic uses of atropine,...

Pharmacology of ANS Anticholinergics Dr. Rajasekhar Chinta Associate Professor of Pharmacology MUCM, Level 09-ACB-01 Learning outcomes Classification of antimuscarinic drugs Pharmacological actions of atropine Therapeutic uses of atropine, scopolamine and glycopyrrolate Adverse effects Atropine poisoning and management Antimuscarinic drugs and their therapeutic uses 2 Introduction Atropa belladonna, Datura – natural source 3 Classification Natural alkaloids: Atropine, Hyoscine, Scopolamine Semisynthetic atropine derivatives: Homatropine, Hyoscine butyl bromide, Ipratropium bromide, Tiotropium bromide. Synthetic compounds:  Mydriatics: Cyclopentolate, Tropicamide. 4 Classification  Antisecretory-antispasmodics:  Quaternary compounds: Propantheline, Oxyphenonium, Isopropamide, Glycopyrrolate.  Tertiary amines: Dicyclomine, Pirenzepine.  Vasicoselective: Oxybutynin, Flavoxate, Tolterodine.  Antiparkinsonian: Trihexyphenidyl (Benzhexol), Procyclidine, Biperiden 5 Pharmacological actions of atropine CNS: Low doses – No effect Therapeutic doses – stimulates various medullary centers – vagal, respiratory, vasomotor center. Depresses vestibular excitation and vomiting center → anti- motion sickness action 6 Pharmacological actions… CNS: Blocks cholinergic overactivity in the basal ganglia → suppresses symptoms of Parkinsonism (benztropine) Cortical excitation, restlessness, disorientation, hallucinations, delirium, followed by respiratory depression and coma (high doses) 7 8 Pharmacological actions… EYE: Blockade of M3 (circular muscle of iris / iris sphincter muscle / pupillary sphincter / pupillary constrictor) → no miosis → unopposed sympathetic α1 stimulation (radial muscle of iris) → dilatation of pupil → passive (indirect) mydriasis Normal pupillary responses are blocked → eyes become unresponsive to light → loss of light reflex Wide pupillary dilatation → photophobia 9 Radial muscle Ciliary muscle Pharmacological actions… EYE: Blocks M3 receptors (ciliary muscle of lens) → no response to cholinergic stimulation → relaxation of ciliary muscle → suspensory ligaments get tightened → flattening of the lens (less convex lens) → eyes get set for distant vision → cycloplegia Rise in intraocular pressure in patients with a narrow anterior chamber angle Dry eyes 11 Pharmacological actions… CVS: Blocks M2 (SA node) → no / ↓ vagal effect → tachycardia (moderate to high dose) AV conduction → shorten the refractory period of AV node → ↑ ventricular rate (patients with atrial flutter or fibrillation) 12 Pharmacological actions… CVS: No marked effect of atropine on BP Higher doses of atropine dilates cutaneous blood vessels especially of the face (atropine flush) – M3 13 Pharmacological actions… Respiratory system: M3 (bronchial smooth muscles) → bronchodilatation & reduces airway resistance M3 (secretory glands of the pulmonary airway) → inhibits secretions (nose, mouth, pharynx and bronchi) → drying of mucus membrane of the respiratory tract → suppression of mucociliary clearance During general anesthesia → reduces tracheobronchial secretions → reduce laryngospasm 14 Pharmacological actions… GIT: M1 (parietal cells of stomach) → ↓ the basal secretion M3 (salivary glands) → ↓ salivary secretion → dry mouth M3 (smooth muscles of GIT) → ↓ tone and motility of the gut → ↑ gastric emptying time, closure of sphincters, ↓ in peristaltic movements → constipation Spasmolytic action → can relax the gut, bile duct and gall bladder 15 Pharmacological actions… Genitourinary tract: M3 (smooth muscles of ureters and urinary bladder) → muscle relaxation → urinary retention 16 Pharmacological actions… Sweat glands: M3 (sweat glands) → suppresses sweating → dry & hot skin Toxic doses → ↑ body temperature, ↓ all body secretions → atropine fever In infants and children below 5 years of age, therapeutic doses of atropine can also cause atropine fever 17 Therapeutic uses of atropine Second degree heart block Scopolamine- Motion sickness Sinus bradycardia Glycopyrrolate- Preanesthetic Preanesthetic medication medication OP and mushroom poisoning Retinal examination; prevention of synechiae (adhesion of iris to lens or cornea) after surgery 18 Adverse effects of atropine Dryness of mouth Blurred vision and photophobia Dry or sandy eyes Precipitation of glaucoma Constipation Urinary retention Decreased sweating, dry and hot skin 19 Atropine poisoning > 80 mg ingestion 100 mg is lethal Manifestations: Dry skin (as dry as bone) - Dry mouth Hyperpyrexia (atropine fever) - Slurred speech Flushing of face (as red as beet) Mydriasis and photophobia (as blind as bat) 20 Manifestations Difficulty in micturition Confusion, delirium, restlessness, hallucinations (as mad as wet hen) Cardiovascular collapse Respiratory paralysis Coma 21 Treatment of atropine poisoning General measures: (symptomatic management is more effective and less dangerous) Hospitalization Gastric lavage Control hyperpyrexia (cooling blankets) Convulsions – Diazepam ANTIDOTE: Physostigmine (1–4 mg in adults, 0.5–1 mg in children) slow i.v. 22  Therapeutic uses Antimuscarinic drugs Motion sickness Scopolamine Benzhexol, benztropine, Parkinson’s disease procyclidine Refractory testing, fundoscopic examinations, iritis, to Tropicamide, break adhesions between lens and cornea in iridocyclitis cyclopentolate, (As mydriatic and cycloplegic) homatropine Sinus bradycardia, AV block (As cardiac vagolytic) Atropine Bronchial asthma and chronic obstructive pulmonary Ipratropium, tiotropium disease (COPD) Preanesthetic medication Glycopyrrolate, atropine Peptic ulcer Pirenzepine, telenzepine Intestinal colic, renal colic, biliary colic, traveler’s Dicyclomine diarrhea, irritable bowel syndrome (As antispasmodics) Urinary incontinence, nocturnal enuresis Flavoxate, oxybutynin Hyperhidrosis, excessive salivation Dicyclomine 23