Anticholinergic Drugs-Nov.2024 PDF

In The Name of God Cholinoceptor Blockers 1 Dr. Marjan Nassiri- Asl Professor of Pharmacology  School of Medicine, Shahid 2 Aims Learn about the classification, mechanism of action and pharmacokinetics of antimuscarinic d...

In The Name of God Cholinoceptor Blockers 1 Dr. Marjan Nassiri- Asl Professor of Pharmacology  School of Medicine, Shahid 2 Aims Learn about the classification, mechanism of action and pharmacokinetics of antimuscarinic drugs Learn the effects of anticholinergic on the major organ systems Learn the major clinical indications, adverse effects and contraindications for the use of muscarinic antagonists Learn the effects of the ganglion-blockers and clinical indications 3 Anticholinergic drugs classification Anticholinergic drugs Loading… Antimuscarinic Antinicotinic 4 Antimuscarinic drugs classification Antimuscarinic drugs M1 Slightly M3 selective Nonselective selective (Atropine) (Darifenacin) (Pirenzepine) May be selective gastrointestinal tract 5 Antimuscarinic drugs Act like competitive pharmacologic antagonists Most of them are relatively nonselective They can also be subdivided based on their Loading… primary clinical target organs (CNS, eye, bronchi, or GIT and GUT) 6 Atropine The prototypical nonselective muscarinic blocker It is eliminated partially by metabolism in the liver and partially unchanged in the urine Half-life 2 h Duration of action of normal doses is 4–8 h except in the eye 72h  Effects of muscarinic blocking drugs 7 Why causes Bradycardia? 8 Clinical Uses 9 Parkinsonism Tremor and rigidity seem to result from a relative excess of cholinergic activity Benztropine, Trihexyphenidyl, Biperiden 10 Benztropine Is sometimes used parenterally to treat acute dystonias caused by first-generation antipsychotic medications❋ ❋ ✻Drug-induced ✻ parkinsonism: Haloperidol, Trifluoperazine, Perphenazine 11 Motion sickness Scopolamine (Hyoscine) Loading… Drowsiness, amnesia in sensitive individuals In toxic doses, can cause excitement, agitation, hallucinations, and coma 12 Eye Clinical uses 1. Accurate measurement of refractive error in uncooperative patients (eg, young children) requires ciliary paralysis 2. Mydriasis greatly facilitates ophthalmoscopic examination of the retina 13 Eye Tropicamide (0.5-4 h) Cyclopentolate (2-12 h) Homatropine (24 h) Atropine (>72 h) Toxicity: Increased IOP in closed-angle glaucoma 14 COPD, Asthma COPD: Chronic Obstructive Pulmonary Disease 15 COPD, Asthma Bronchodilator Ipratropium (t1/2 2 h) Longer duration of Tiotropium (t½ 25 h) action Aclidinium (t½ 6 h) Umeclidinium (t½ 11 h) Glycopyrrolate (t ½ 1.2 h) Asthma 16 Combination therapy for the inhalation treatment of COPD Antimuscarinic drugs + long-acting β2-adrenoceptor agonists 17 Atropine Parenteral has long been used to reduce airway secretions during general anesthesia 18 Gastrointestinal Disorders 1. Can provide some relief in the treatment of common traveler’s diarrhea 2. Other mild or self-limited conditions of hypermotility 19 Gastrointestinal Disorders Dicyclomine Clidinium Scopolamine (Hyoscine) Hyoscyamine Atropine + diphenoxylate Anti-diarrheal drug 20 Pirenzepine M1-selective inhibitor For treatment of peptic ulcer (in Europe) 21 Cholinergic Poisoning Atropine sulfate Reduces the muscarinic signs of poisoning with AChE inhibitors Pralidoxime Regenerates active AChE  Urinary Disorders 22 1- Reduce bladder spasms after urologic surgery, e.g., prostatectomy Oxybutynin 23 Urinary Disorders 2-Urinary incontinence Slightly M3-selective antimuscarinics 1. Tolterodine 2. Darifenacin 3. Solifenacin 4. Fesoterodine Selectivity for M3 receptors than oxybutynin/once-daily dosing 24 Cardiovascular disorders Vasovagal attack (vagal discharge) May experience faintness or even syncope Hyperactive carotid sinus reflexes in response to pressure on the neck, e.g., from a tight collar Parenteral atropine or a similar antimuscarinic drug is appropriate therapy 25 Adverse Effects Hyperthermia Hot, dry flushed skin Dry mouth Tachycardia Amnesia, delirium, agitation, hallucinations Constipation Urinary retention Mydriasis, blurred vision 26 Cutaneous vasodilation At toxic doses, antimuscarinic agents cause, esp. in the upper portion of the body The mechanism is unknown 27 Treatment of toxicity Treatment of toxicity is usually symptomatic Severe tachycardia may require cautious administration of small doses of physostigmine Hyperthermia can usually be managed with cooling blankets or evaporative cooling 28 Contraindication In infants because of the danger of hyperthermia Glaucoma (esp. close angel) In elderly men with a history of prostatic hyperplasia In erectile dysfunction since acetylcholine plays a role in smooth muscle relaxation in genital erectile tissue 29 Cholinesterase Regenerators Pralidoxime (PAM) Is the prototype cholinesterase regenerator These chemical antagonists contain an oxime group ( NOH), Loading… which has an extremely high affinity for the phosphorus atom in organophosphate insecticides 30 It is not recommended for use in carbamate AChE inhibitor overdosage 31 Antinicotinic classification 32 Ganglion-Blocking Drugs Competitive pharmacologic antagonists Some also block the pore of the nicotinic channel itself The first successful agents for the treatment of hypertension Now obsolete for this indication 33 Ganglion-Blocking Drugs Hexamethonium Mecamylamine 34 Mecamylamine A nicotinic ganglion blocker Enters the CNS Some benefits in smoking cessation  Toxicity Inte 35 rrup t sym path etic Ganglion blockers cont rol of veno us tone Marked venous pooling Postural hypotension 36 Other Toxicity Rarely used in clinical practice 37 Neuromuscular-Blocking Drugs Produce marked skeletal muscle relaxation that is important in: 1. Surgery 2. Mechanical ventilation of patients Atracurium, Vecuronium 38 Summary Describe classification, mechanism of action and pharmacokinetics of antimuscarinic drugs Describe the effects of anticholinergic on the major organ systems You can describe the major clinical indications, adverse effects and contraindications for the use of muscarinic antagonists Describe the effects of the ganglion-blockers and clinical indications 39 Reference 1. Bertram G. Katzung, Marieke Kruidering-Hall, Anthony J. Trevor. Katzung & Trevor's Pharmacology: Examination & Board Review, 13e. 2021, McGraw-Hill Education, Ch 8 2. Bertram G. Katzung, Todd W Vanderah. Basic and Clinical Pharmacology, 16e. 2023, McGraw-Hill Education, Ch 8 40 Thanks for Your Attention [email protected]