anticholinergics Pharmacology 2nd MBBS CBME.pptx

pharmacology of atropine ans its substitutes

1. Dr. A. Sirisha MBBS, MD Dept . Of Pharmacology Atropine & Atropine Substitutes 11/18/2024 Dr Sirisha A

2. PH 1.14 Describe mechanism of action, types, doses, side effects , indications and contraindications of cholinergic and anticholinergic drugs 11/18/2024 Dr Sirisha A Competency

3. To Classify , describe the mechanism of action, indications, contra indications, adverse effects of anti cholinergics . To compare and contrast atropine and scopolamine. To classify atropine substitutes based on their indications giving examples of drugs To justify drug/s of choice for various functional abnormalities of micturition 11/18/2024 Dr Sirisha A SLO

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7. Drugs opposing the action of Acetyl Choline ( ACh ) : Anti Muscarinic drugs / Atropine related drugs : act mainly at post ganglionic cholinergic nerve endings. Anti Nicotinic Drugs Ganglion Blocking drugs Neuromuscular blocking drugs 11/18/2024 Dr Sirisha A Introduction

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9. Muscarinic receptor antagonists / Atropinic / Parasympatholytic drugs Eg ., Atropine and related alkaloids Plant sources : Atropine – prototype drug Introduction 11/18/2024 Dr Sirisha A Atropa Belladona Atropa acuminata Hyoscyamus niger Scopola carnioloca Datura strontium

10. Atropa belladonna 11/18/2024 Dr Sirisha A

11. Blockade of muscarinic receptors M1- Autonomic ganglia, Gastric glands, Enteric neurones, CNS M2 - Heart, Nerve endings, Visceral smooth muscles M3 – Visceral and bronchial smooth muscles, Eye, Exocrine glands, Vascular endothelium 11/18/2024 Dr Sirisha A Mechanism of action

12. 11/18/2024 Dr Sirisha A Mechanism of action

13. CNS: Over all stimulant action Stimulates - Vagal, respiratory, vasomotor. ↓ vestibular excitation - Anti motion sickness property. ACh in basal ganglia - suppresses tremor & rigidity of parkinsonism. High doses - cortical excitation, restlessness, disorientation, hallucinations, delirium f/b Resp. depression & coma 11/18/2024 Dr Sirisha A Atropine : Pharmacological Actions

14. Blocks M 2 receptors on SA node. On IM/SC inj. – transient initial bradycardia Abbreviates refractory period of A-V node & facilitates A-V conduction. PR interval is shortened. 11/18/2024 Dr Sirisha A Pharmacological actions : CVS ACH M 2 receptors on heart ↓ HR Atropine ↑ HR

15. Blood Pressure : No marked effect ↑HR & VMC stimulation - ↑BP while Histamine release & direct vasodilatation(at high doses) - ↓ BP 11/18/2024 Dr Sirisha A Pharmacological actions : CVS

16. 11/18/2024 Dr Sirisha A Autonomic control on Pupil

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18. Topical instillation – Mydriasis Abolition of light reflex Cycloplegia Resulting in photophobia, blurring of near vision. ↑ Intra ocular tension (specially in narrow angle glaucoma). Ciliary muscles recover earlier than sphincter pupillae 11/18/2024 Dr Sirisha A Atropine Actions : On Eye for 7-10 days

19. Relaxation of all visceral smooth muscle (M 3 blocker) GIT : Tone & amplitude of contractions ↓(stomach & intestine) Passage of chyme is slowed- constipation occurs & spasm relieved. Resp. system : Bronchodilatation & ↓ air way resistance in COPD & asthma. Atropine : On Smooth muscles 11/18/2024 Dr Sirisha A

20. Urinary bladder & Ureter : Relaxes ureter & bladder - urinary retention esp. in older ♂ with prostate hypertrophy. Beneficial for ↑ bladder capacity & controlling detrusor hyper reflexia in neurogenic bladder / enuresis. Biliary tract and Uterus : minimal action 11/18/2024 Dr Sirisha A Atropine : Pharmacological Actions

21. Glands: ↓ sweat, salivary, tracheo -bronchial & lacrimal secretions (M 3 blockade) Skin – dry, talking & swallowing may be difficult ↓ acid, pepsin & mucus secretion in stomach & ↓ bicarbonate secretion also. But ↑ PH is modest. Intestinal & pancreatic secretions not ↓ much B ile is not under cholinergic control – not affected. 11/18/2024 Dr Sirisha A Atropine : Pharmacological Actions

22. Body temperature: ↑ in high doses Due to inhibition of sweating Stimulation of temp. regulating centre in hypothalamus. Children are more susceptible to atropine fever . Local anaesthetic: mild action on cornea. Atropine : Pharmacological Actions 11/18/2024 Dr Sirisha A

23. The sensitivity of different organs and tissues of atropine varies and can be graded as- Saliva, sweat, bronchial secretions > Bronchial muscle, heart > smooth mus., intestine, bladder > gastric glands. 11/18/2024 Dr Sirisha A Atropine : Pharmacological Actions

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25. Dry mouth, difficulty in swallowing & talking Dry, flushed, hot skin (esp. over neck & face), fever Difficulty in micturition , ↓ bowel sounds, scarlet rash. Dilated pupil, photophobia, blurring of vision. Palpitation Excitement, psychotic behaviour, ataxia, delirium, visual hallucinations. Hypotension, weak & rapid pulse, collapse, respiratory depression Severe poisoning - Convulsions & coma. 11/18/2024 Dr Sirisha A Side Effects And Toxicity

26. Belladona poisoning may occur due to drug over dose or consumption of seeds & berries of Belladona / Datura plant Signs & symptoms : Exaggeration of pharmacological actions occur. 11/18/2024 Dr Sirisha A Atropine Toxicity

27. Diagnosis : Methacholine 5mg / Neostigmine 1mg fails to induce Muscarinic symptoms Treatment: Gastric lavage with tannic acid (KMnO 4 is ineffective) P t. should be kept in a dark quiet room Cold sponging or ice bags for ↓ temperature Physostigmine 1-3mg SC / IV Repeated 4 th - 6 th hrly . Other measures like maintenance of CAB, Diazepam to control convulsions. 11/18/2024 Dr Sirisha A Atropine Toxicity

28. Contraindications: Absolutely CI in narrow iridocorneal angle Caution in elderly males with prostatic hypertrophy. Atropine 11/18/2024 Dr Sirisha A

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30. Introduced for better therapeutic selectivity. Either synthetic /semi synthetic Chemically either Quarternary Ammonium compounds or Tertiary amines 11/18/2024 Dr Sirisha A ATROPINE Substitutes

31. Differences Quaternary Ammonium drugs Tertiary amine drugs Lipid insoluble Lipid soluble Orally Not well absorbed Well absorbed Elimination is slower & majority are longer acting better elimination Does not cross BBB Crosses BBB Exhibit greater degree of Nicotinic blocking action, ganglionic blockade - postural hypotension, impotence More selective for Muscarinic receptors 11/18/2024 Dr Sirisha A

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33. Acts selectively on Bronchial muscle (larger central airways ) does not depress mucociliary clearance by bronchial epithelium, has no anti secretory action Gradual onset & late peak (60-90mts), acts for 4-6 hrs Uses : Suitable for regular prophylactic use of bronchial asthma. More effective in COPD. Dose : 40-80mcg by inhalation ADR : local :- Dryness of mouth, scratching in trachea, cough, bad taste, nervousness. 11/18/2024 Dr Sirisha A Ipratropium bromide

34. Long acting Muscarinic antagonist (LAMA) Given inhalational 11/18/2024 Dr Sirisha A Tiotropium bromide

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36. Anti secretory anti spasmodic drug Uses : Nervous dyspepsia, Gastritis, Irritable bowel syndrome ( IBS), Colic 11/18/2024 Dr Sirisha A Clidinium

37. Anti secretory Potent & rapidly acting without central effects Uses : Pre- anaesthetic medication & during anaesthesia - parenteral COPD – inhalational( LAMA). 11/18/2024 Dr Sirisha A Glycopyrrolate

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39. Smooth muscle relaxant , antiemetic 20mg oral/IM, Uses : Motion sickness, morning sickness, dysmenorrhoea , IBS 11/18/2024 Dr Sirisha A Dicyclomine

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41. Other drugs: Darifenacin , Solifenacin 11/18/2024 Dr Karuna Sree, Dept. Of Pharmacology, KIMS Vasicoselective drugs Drug Uses Oxybutynin : M1/M3 receptors in urinary bladder, salivary glands with addt . Sm musc . Relaxant & local aneasthetic property Urinary frequency, urge incontinence in c/o neurogenic bladder, spina bifida, nocturnal enuresis Tolterodine : M3 selective Urinary frequency & urgency Flavoxate Urinary frequency & urgency with LUTI

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43. Non- anticholinergic smooth muscle relaxant MOA : Inhibits phophodiesterase (PDE-4) enzyme → cAMP / cGMP levels → mus. relaxation Uses : Intestinal, biliary , renal colic, IBS, uterine spasms Dose : 40-80 mg ADR : Headache, Dizziness, Constipation, Flushing. On IV inj. Fall in BP 11/18/2024 Dr Sirisha A Drotaverine

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46. Drug Dose Uses Homatropine 10 times less potent. Onset : 45-60 min. 1% or 2% drops Mydriasis : 1-3 days Accomodation : 1-2days. Mydriatic Cyclopentolate Potent & rapidly acting Onset : 30-60min. 0.5 – 1% eye drops DOA -1 day. Cycloplegic Refraction, iritis , uveitis Tropicamide Quickest (20-40 min) & briefest (3-6 hrs) 0.5-1% eye drops Refractive errors, fundoscopy 11/18/2024 Dr Sirisha A Mydriatics

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48. Trihexyphenidyl ( benzhexol ), Orphenadrine , Procyclidine , Biperiden . 10-25% improvement in cl.features (improvement : tremor> R igidity > hypokinesia ) Sialorrhoea improved – peripheral effect. Uses : given alone in mild cases of parkinson’s disease / usually combined levodopa Drug induced parkinsonism 11/18/2024 Dr Sirisha A Anti parkinsonian drugs

49. 11/18/2024 Dr Sirisha A Uses

50. Preanaesthetic medication : to ↓ secretions, prevent laryngospasm & vasovagal attack. Peptic ulcer : ↓ gastric secretions of fasting, neurogenic phase. Pulmonary embolism : ↓ reflux secretions Parkinsonism : ↓ excessive sweating, salivation 11/18/2024 Dr Sirisha A Antisecretory Uses

51. Intestinal, renal colic, abdominal Cramps NOT EFFECTIVE IN BILIARY COLIC Nervous, drug induced & functional diarrhoea Spastic constipation, irritable bowel syndrome Pylorospasm , gastritis, nervous dyspepsia, gastric hypermotility To relieve urinary frequency & urgency, enuresis in children Dysmenorrhea 11/18/2024 Dr Sirisha A Antispasmodic Uses

52. Bronchial Asthma, Asthmatic Bronchitis, COPD. As mydriatic & cycloplegic : Diagnostic : Refractive error testing Therapeutic : Iritis , Iridocyclitis,choroiditis,keratitis , Corneal Ulcer As Cardiac vagolytic : in counteracting bradycardia / partial heart block 11/18/2024 Dr Sirisha A Uses

53. For Central action : Parkinsonism Motion sickness Hyoscine : Sedation & amnesia during labour (Twilight sleep), to control maniacal states & as lie detector. 11/18/2024 Dr Sirisha A Uses

54. To antagonise muscarinic effects of drugs & poisons : Anticholinesterase, mushroom poisoning. To block the muscarinic actions of neostigmine 11/18/2024 Dr Sirisha A Uses

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57. Anticholinergic drugs are the muscarinic receptor blockers and atropine is the prototype drug. Main actions are ↑ HR, relaxes smooth muscles, ↓secretions and central effects. Atropine substitutes are used as anti secretory , antispasmodic, brochial asthma/COPD, mydriatics , antiparkinsons , vagolytic drugs. 11/18/2024 Dr Sirisha A Summary

58. Which of the responses to atropine listed below is most likely to be different in an elderly versus a young patient? (A) Inhibition of sweating (B) Tachycardia (C) Mydriasis (D) Drowsiness 11/18/2024 Dr Sirisha A MCQ 1

59. An elderly male aged 74 years was brought to the hospital since he had not passed urine for the past 24 hours and had severe pain in lower abdomen. On examination there was a bulge in the pubic region due to full urinary bladder. On catheterization, he passed 1.5L urine and the pain was relieved. He gave the history of having difficulty in passing urine, poor stream, frequent urge to urinate and post-void dribbling for the last 3 years. Over the past few days he had been experiencing episodes of vertigo for which he was prescribed a medicine that he was taking for 2 days. Examination of the prescription revealed that he was taking tab. Dimenhydrinate 50 mg 3 times daily. Could there be any relationship between the anti-vertigo medication and the episode of acute urinary retention? 11/18/2024 Dr Sirisha A Case study 1

60. Dimenhydrinate is a H1 antihistaminic- antivertigo drug with potent antimuscarinic action. Since muscarinic cholinoceptors mediate neurogenic contraction of the detrusor muscle, antimuscarinic drugs interfere with vesical contractions needed for urination. Elderly men with benign hypertrophy of prostate have bladder neck obstruction and are prone to develop urinary retention as a side effect of antimuscarinic drugs. This patient has history indicative of prostatic hypertrophy. 11/18/2024 Dr Sirisha A Case study 1

61. A 50-year-old male farm worker is brought to the emergency room. He was found confused in the orchard and since then has lost consciousness. His heart rate is 45, and his blood pressure is 80/40 mm Hg. He is sweating and salivating profusely. Which of the following treatments is indicated? A. Physostigmine . B. Norepinephrine. C. Trimethaphan . D. Atropine. E. Edrophonium . 11/18/2024 Dr Sirisha A MCQ 2

62. A 75-year-old man who was a smoker is diagnosed with chronic obstructive pulmonary disease and suffers from occasional bronchospasm. Which of the following would be effective in treating him? A. Ipratropium aerosol. B. Scopolamine patches. C. Mecamylamine . D. Oxygen. 11/18/2024 Dr Sirisha A MCQ 3