ANTICHOLINERGIC DRUG1 BY GULSHAN ATHBHAIYA.docx

ANTICHOLINERGIC DRUG1 BY GULSHAN ATHBHAIYA.docx

• 1.
  ANTICHOLIERGIC DRUGS |Gulshan A ANTICHOLINERGIC DRUGS - EASY NOTES DEFINITION Drugs that block or inhibit the action of acetylcholine at cholinergic receptors CLASSIFICATION A. ANTIMUSCARINIC DRUGS (Muscarinic Antagonists) 1. NATURALALKALOIDS  Atropine (from Atropa belladonna)  Scopolamine (Hyoscine)  Homatropine 2. SEMI-SYNTHETIC  Ipratropium  Tiotropium  Atropine methylnitrate 3. SYNTHETIC DRUGS a) Mydriatics/Cycloplegics:  Tropicamide  Cyclopentolate b) Antispasmodics:  Dicyclomine  Propantheline  Hyoscine butylbromide c) Antiparkinsonian:  Trihexyphenidyl (Benzhexol)  Benztropine  Biperiden  Procyclidine d) Bronchodilators:  Ipratropium  Tiotropium e) Antisecretory:  Pirenzepine
• 2.
  ANTICHOLIERGIC DRUGS |Gulshan A  Propantheline f) Urinary Antispasmodics:  Oxybutynin  Tolterodine  Solifenacin  Darifenacin B. ANTINICOTINIC DRUGS 1. Ganglionic Blockers  Mecamylamine  Trimethaphan (Covered separately) 2. Neuromuscular Blockers  Tubocurarine  Pancuronium (Separate category) MECHANISM OF ACTION Antimuscarinic Drugs  Action: Competitive antagonism at muscarinic (M) receptors  Block: M1, M2, M3, M4, M5 receptors  Result: Inhibit parasympathetic effects  Reversible: Can be overcome by high ACh concentrations Receptor Types:  M1: CNS, gastric parietal cells  M2: Heart (SA node, AV node)  M3: Smooth muscles, glands, eyes  M4 & M5: CNS PHARMACOLOGICALACTIONS 1. CARDIOVASCULAR SYSTEM Low Dose:  Slight bradycardia (central effect)
• 3.
  ANTICHOLIERGIC DRUGS |Gulshan A Therapeutic Dose:  ↑ Heart rate (tachycardia)  ↑ Cardiac output  Improved AV conduction  Prevents vagal bradycardia Effects:  Blocks M2 receptors in heart  Removes parasympathetic tone 2. SMOOTH MUSCLES GI Tract:  ↓ Motility (antispasmodic)  ↓ Tone  ↓ Peristalsis  Relaxation Bronchi:  Bronchodilation  ↓ Secretions  Useful in COPD, asthma Urinary Bladder:  ↓ Detrusor tone  Urinary retention  ↑ Bladder capacity Biliary Tract:  Relaxation  Antispasmodic 3. GLANDS (Antisecretory)  ↓ Salivation (dry mouth)  ↓ Sweating  ↓ Bronchial secretions  ↓ Gastric acid secretion
• 4.
  ANTICHOLIERGIC DRUGS |Gulshan A  ↓ Lacrimation 4. EYES Pupil:  Mydriasis (pupil dilation)  Cycloplegia (paralysis of accommodation)  ↑ Intraocular pressure (in glaucoma patients)  Photophobia 5. CENTRAL NERVOUS SYSTEM Low Doses:  Sedation (scopolamine)  Antiemetic effect  Prevention of motion sickness Therapeutic Doses:  Stimulation  Restlessness  Antiparkinsonian effect Toxic Doses:  Confusion  Hallucinations  Delirium  Coma INDIVIDUAL DRUGS - DOSES & USES 1. ATROPINE Dose:  Oral: 0.5-1 mg  IV/IM/SC: 0.4-0.6 mg  Premedication: 0.6 mg IM  Bradycardia: 0.5-1 mg IV (repeat if needed)
• 5.
  ANTICHOLIERGIC DRUGS |Gulshan A  Organophosphate poisoning: 2-4 mg IV every 5-10 min Uses: ✓ Cardiac: Bradycardia, heart block ✓ Premedication: Before anesthesia (↓ secretions) ✓ Poisoning: Organophosphate, cholinergic overdose ✓ Ophthalmology: Mydriasis, cycloplegia ✓ GI spasms: Antispasmodic ✓ Asthma: Emergency bronchodilator Special Features:  Prototype antimuscarinic drug  Crosses blood-brain barrier  Duration: 4-6 hours 2. SCOPOLAMINE (HYOSCINE) Dose:  Oral/IM/SC: 0.3-0.6 mg  Patch: 1.5 mg (72 hours)  Motion sickness: 0.6 mg 30 min before travel Uses: ✓ Motion sickness (drug of choice) ✓ Premedication (sedation + antisecretory) ✓ Postoperative nausea and vomiting ✓ Parkinsonism Special Features:  More CNS effects than atropine  Strong sedative and antiemetic  Causes amnesia  Better for motion sickness 3. IPRATROPIUM BROMIDE Dose:  Inhaler: 20-40 mcg, 3-4 times/day  Nebulizer: 250-500 mcg, 3-4 times/day  Nasal spray: 21-42 mcg per nostril
• 6.
  ANTICHOLIERGIC DRUGS |Gulshan A Uses: ✓ COPD (drug of choice) ✓ Asthma (with beta-agonists) ✓ Rhinorrhea Special Features:  Quaternary compound (doesn't cross BBB)  Minimal systemic effects  Onset: 15 min, Duration: 4-6 hours 4. TIOTROPIUM Dose:  Inhaler: 18 mcg once daily (HandiHaler)  Spray: 2.5 mcg, 2 puffs daily Uses: ✓ COPD maintenance (preferred) ✓ Long-term bronchodilation Special Features:  Long-acting (24 hours)  Once-daily dosing  M3 receptor selective 5. TROPICAMIDE Dose:  Eye drops: 0.5-1%  Apply 1-2 drops Uses: ✓ Mydriasis for fundoscopy ✓ Cycloplegia for refraction Special Features:  Short duration (4-6 hours)  Rapid onset (20-40 min)  Preferred for examination 6. CYCLOPENTOLATE
• 7.
  ANTICHOLIERGIC DRUGS |Gulshan A Dose:  Eye drops: 0.5-2% Uses: ✓ Cycloplegia for refraction (children) ✓ Mydriasis Special Features:  Duration: 6-24 hours  Stronger cycloplegia than tropicamide 7. HOMATROPINE Dose:  Eye drops: 2-5% Uses: ✓ Mydriasis ✓ Uveitis (to prevent adhesions) Special Features:  Intermediate duration (1-3 days)  Less potent than atropine 8. TRIHEXYPHENIDYL (BENZHEXOL) Dose:  Oral: 2-5 mg, 3 times/day  Maximum: 15 mg/day Uses: ✓ Parkinson's disease (tremor control) ✓ Drug-induced parkinsonism ✓ Dystonia Special Features:  Reduces tremor and rigidity  Less effective for bradykinesia  CNS penetration 9. BENZTROPINE Dose:
• 8.
  ANTICHOLIERGIC DRUGS |Gulshan A  Oral/IM/IV: 0.5-6 mg/day  Acute dystonia: 1-2 mg IM/IV Uses: ✓ Parkinson's disease ✓ Drug-induced extrapyramidal symptoms ✓ Acute dystonia Special Features:  Anticholinergic + antihistaminic  Also has dopamine reuptake inhibition 10. DICYCLOMINE (DICYCLOVERINE) Dose:  Oral: 10-20 mg, 3-4 times/day  IM: 20 mg, 4 times/day Uses: ✓ Irritable bowel syndrome (IBS) ✓ Abdominal cramps ✓ Infantile colic Special Features:  Direct smooth muscle relaxant  GI selective 11. HYOSCINE BUTYLBROMIDE (BUSCOPAN) Dose:  Oral: 10-20 mg, 3-4 times/day  IM/IV: 20 mg Uses: ✓ Abdominal cramps ✓ Renal/biliary colic ✓ IBS ✓ GI spasms Special Features:  Quaternary compound  Doesn't cross BBB  Fewer CNS effects
• 9.
  ANTICHOLIERGIC DRUGS |Gulshan A 12. PROPANTHELINE Dose:  Oral: 15 mg, 3 times/day + 30 mg at bedtime Uses: ✓ Peptic ulcer ✓ Urinary incontinence ✓ Hyperhidrosis (excessive sweating) 13. PIRENZEPINE Dose:  Oral: 50 mg twice daily Uses: ✓ Peptic ulcer disease Special Features:  M1 receptor selective  Selective for gastric acid secretion  Fewer side effects 14. OXYBUTYNIN Dose:  Oral: 5 mg, 2-3 times/day  Patch: 3.9 mg twice weekly Uses: ✓ Urge incontinence ✓ Overactive bladder ✓ Neurogenic bladder ✓ Nocturnal enuresis Special Features:  Also has direct smooth muscle relaxant effect  Available as patch (fewer side effects) 15. TOLTERODINE Dose:
• 10.
  ANTICHOLIERGIC DRUGS |Gulshan A  Oral: 2 mg twice daily  ER: 4 mg once daily Uses: ✓ Overactive bladder ✓ Urge incontinence Special Features:  Bladder selective  Fewer side effects than oxybutynin 16. SOLIFENACIN Dose:  Oral: 5-10 mg once daily Uses: ✓ Overactive bladder ✓ Urge incontinence Special Features:  M3 receptor selective  Once-daily dosing SIDE EFFECTS (Common) Remember: "Anti-SLUDGE" (Opposite of cholinergic) Mouth:  Dry mouth (xerostomia) ★★★  Difficulty swallowing Eyes:  Blurred vision  Photophobia  Mydriasis  Loss of accommodation Skin:  Dry skin  Flushing  Hyperthermia (no sweating)
• 11.
  ANTICHOLIERGIC DRUGS |Gulshan A GI:  Constipation  Decreased motility GU:  Urinary retention  Hesitancy CVS:  Tachycardia  Palpitations CNS:  Confusion (elderly)  Drowsiness or restlessness  Headache ADVERSE EFFECTS (Serious) Atropine Toxicity Mild to Moderate:  Dry mouth, thirst  Dilated pupils  Tachycardia  Hot, flushed skin  Fever  Agitation Severe:  Hyperthermia (very high fever)  Delirium  Hallucinations  Seizures  Coma  Respiratory failure  Death Classic Description:
• 12.
  ANTICHOLIERGIC DRUGS |Gulshan A "Red as a beet, Dry as a bone, Blind as a bat, Mad as a hatter, Hot as a hare"  Red: Flushed skin  Dry: No sweating, dry mouth  Blind: Mydriasis, blurred vision  Mad: Confusion, delirium  Hot: Hyperthermia DRUG INTERACTIONS 1. OTHER ANTICHOLINERGICS  Examples: Antihistamines, TCAs, phenothiazines  Effect: Additive anticholinergic effects  Risk: Severe dry mouth, constipation, confusion 2. CHOLINERGIC DRUGS  Examples: Neostigmine, pilocarpine  Effect: Mutual antagonism  Result: Reduced effectiveness of both 3. ANTACIDS  Effect: ↓ Absorption of anticholinergics  Management: Give 1-2 hours apart 4. ANTIARRHYTHMICS  Examples: Quinidine, disopyramide  Effect: Enhanced anticholinergic effects  Risk: Severe tachycardia 5. ALCOHOL & CNS DEPRESSANTS  Effect: Enhanced CNS depression (with scopolamine)  Risk: Excessive sedation 6. PHENOTHIAZINES & TCAs  Effect: Additive antimuscarinic effects  Risk: Paralytic ileus, hyperthermia 7. LEVODOPA  Effect: Decreased GI motility  Result: ↑ Levodopa absorption
• 13.
  ANTICHOLIERGIC DRUGS |Gulshan A 8. DIGOXIN  Effect: Increased digoxin absorption  Risk: Digoxin toxicity CONTRAINDICATIONS Absolute: 1. Angle-Closure Glaucoma ★★★  Mydriasis blocks drainage  ↑ Intraocular pressure  Risk of acute attack 2. Prostatic Hypertrophy (BPH)  Urinary retention worsens  Acute retention risk 3. Pyloric Stenosis  Further delays gastric emptying 4. Paralytic Ileus  ↓ GI motility worsens condition 5. Myasthenia Gravis  Worsens muscle weakness 6. Tachyarrhythmias  Further increases heart rate 7. Obstructive Uropathy  Urinary retention Relative Contraindications:  Elderly patients (confusion risk)  Hyperthyroidism  Coronary artery disease  Heart failure  Hypertension  Chronic lung disease  Hepatic/renal impairment
• 14.
  ANTICHOLIERGIC DRUGS |Gulshan A  Down syndrome (sensitive)  Hot weather (hyperthermia risk) THERAPEUTIC USES - DETAILED 1. CARDIOVASCULAR Sinus Bradycardia:  Atropine 0.5-1 mg IV  Repeat every 3-5 min (max 3 mg) Heart Block:  Atropine (temporary measure) During Anesthesia:  Prevent vagal bradycardia 2. OPHTHALMOLOGY Mydriasis for Examination:  Tropicamide (short-acting)  Cyclopentolate Refraction:  Cyclopentolate (children)  Homatropine Uveitis:  Atropine eye drops (prevent adhesions)  Homatropine 3. RESPIRATORY COPD:  Ipratropium (first-line)  Tiotropium (maintenance) Asthma:  Ipratropium (adjunct to β-agonists) Reduce Secretions:  Atropine in premedication
• 15.
  ANTICHOLIERGIC DRUGS |Gulshan A 4. GASTROINTESTINAL IBS:  Dicyclomine  Hyoscine butylbromide Peptic Ulcer:  Pirenzepine (M1 selective)  Propantheline Abdominal Cramps:  Hyoscine butylbromide  Dicyclomine Biliary/Renal Colic:  Hyoscine butylbromide + analgesic 5. URINARY SYSTEM Overactive Bladder:  Oxybutynin  Tolterodine  Solifenacin Urge Incontinence:  Tolterodine (preferred)  Darifenacin Nocturnal Enuresis:  Oxybutynin 6. CENTRAL NERVOUS SYSTEM Parkinson's Disease:  Trihexyphenidyl  Benztropine  Procyclidine Drug-Induced Parkinsonism:  Benztropine
• 16.
  ANTICHOLIERGIC DRUGS |Gulshan A  Trihexyphenidyl Motion Sickness:  Scopolamine (drug of choice)  Patch or oral 7. ANESTHESIA Premedication:  Atropine (↓ secretions, prevent bradycardia)  Scopolamine (sedation + antisecretory) During Surgery:  Prevent vagal reflexes 8. POISONING Organophosphate Poisoning:  Atropine: 2-4 mg IV, repeat every 5-10 min  Continue until atropinization  Plus Pralidoxime (PAM) Cholinergic Drug Overdose:  Atropine (muscarinic effects) Mushroom Poisoning (Muscarine):  Atropine 9. OTHER USES Hyperhidrosis:  Propantheline  Oxybutynin Rhinorrhea:  Ipratropium nasal spray Drooling (sialorrhea):  Glycopyrrolate ANTIDOTE FOR ANTICHOLINERGIC TOXICITY
• 17.
  ANTICHOLIERGIC DRUGS |Gulshan A Physostigmine Dose:  1-2 mg IV slowly (over 5 min)  Repeat after 20 min if needed  Pediatric: 0.02 mg/kg Indications:  Severe anticholinergic poisoning  CNS effects (delirium, coma)  Only when diagnosis is certain Mechanism:  Acetylcholinesterase inhibitor  Crosses blood-brain barrier  Reverses both peripheral and central effects Caution:  Can cause cholinergic crisis  Monitor closely  Have atropine ready COMPARISON TABLE Drug Duration Main Use Route Special Feature Atropine 4-6 hrs Bradycardia, poisoning All routes Prototype, crosses BBB Scopolamine 4-6 hrs Motion sickness PO, patch, IM Strong CNS effect Ipratropium 4-6 hrs COPD, asthma Inhaled No CNS effects Tiotropium 24 hrs COPD maintenance Inhaled Once daily Tropicamide 4-6 hrs Mydriasis (exam) Eye drops Short-acting Trihexyphenidyl 6-12 hrs Parkinsonism Oral Tremor control Oxybutynin 6-10 hrs Overactive bladder PO, patch Direct muscle effect Tolterodine 6-8 hrs Urge incontinence Oral Bladder selective Dicyclomine 4-6 hrs IBS Oral, IM GI selective SELECTIVE ANTIMUSCARINIC DRUGS
• 18.
  ANTICHOLIERGIC DRUGS |Gulshan A M1 Selective:  Pirenzepine → Gastric acid secretion M2 Selective:  None clinically available M3 Selective:  Tiotropium → Bronchodilation  Darifenacin → Bladder  Solifenacin → Bladder Advantage of Selectivity:  Fewer side effects  Better tolerability  Targeted action QUICK MNEMONICS Anticholinergic Side Effects: "Blind as a Bat, Red as a Beet, Dry as a Bone, Mad as a Hatter, Hot as a Hare" Uses: "BPUG-MO"  Bradycardia  Parkinsonism  Urinary incontinence  GI spasms  Motion sickness  Organophosphate poisoning Contraindications: "GAP-PM"  Glaucoma (angle-closure)  Arrhythmias (tachycardia)  Prostatic hypertrophy  Pyloric stenosis  Myasthenia gravis SPECIAL POPULATIONS Elderly:
• 19.
  ANTICHOLIERGIC DRUGS |Gulshan A  More sensitive to CNS effects  Higher risk of confusion, falls  Start with low doses  Monitor closely Children:  Risk of hyperthermia  More susceptible to toxicity  Use with caution Pregnancy:  Category B or C (most drugs)  Use only if benefit > risk  Crosses placenta EXAM FOCUS POINTS ✓ Atropine = Bradycardia + organophosphate poisoning ✓ Scopolamine = Motion sickness (drug of choice) ✓ Ipratropium/Tiotropium = COPD ✓ Tropicamide = Short-acting mydriatic for examination ✓ Physostigmine = Antidote for anticholinergic toxicity (crosses BBB) ✓ Trihexyphenidyl = Parkinson's tremor ✓ Oxybutynin/Tolterodine = Overactive bladder ✓ Contraindication = Angle-closure glaucoma (most important) ✓ Classic toxicity = "Red as beet, Dry as bone, Blind as bat, Mad as hatter, Hot as hare"