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Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
Anticholinergics (updated 2011) - drdhriti
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Anticholinergics (updated 2011) - drdhriti

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An updated PowerPoint presentation on Anticholinergic drugs suitable for UG MBBS level Medical students

An updated PowerPoint presentation on Anticholinergic drugs suitable for UG MBBS level Medical students

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  • Phenyl trimethyl ammonium
  • Transcript

    • 1. Anticholinergic Drugs Department of Pharmacology NEIGRIHMS, Shillong
    • 2. Introduction
      • Parasympathetic Nervous System plays an important Role in physiologic and pathophysiologic responses - “Rest and Digest”
      • Drugs that block Cholinoreceptors have important clinical effects, some of which are of great clinical value
      • Cholinoceptor antagonists are, like agonists - Muscarinic and Nicotinic
      • Antinicotinic – ganglion blockers and MN junction blockers
        • Discussed elsewhere (SMR Chapter)
      • Muscarinic blockers
        • Atropine is the prototype – many synthetic and semi synthetics are available now
        • All are competitive blockers
    • 3.
      • Recall - Muscarinic (M) and Nicotinic (N) Receptors:
      Muscarinic (M) - GPCR Nicotinic (N) – ligand gated
    • 4. Muscarinic Receptor Subtypes: M 1 , M 2 , M 3 , M 4 and M 5 M1 M2 M3 Location Autonomic ganglia, Gastric glands and CNS Heart and CNS SMs of Viscera, Eye, exocrine glands and endothelium Functions EPSP & Histamine release & acid secretion with CNS learning and motor functions Less impulse generation, less velocity of conduction, decreased contractility, less Ach release Visceral SM contraction, Constriction of pupil, contraction of Cilliary muscle and vasodilatation Agonists Oxotremorine and MCN and MCN-343A Methacholine Bethanechol Antagonists Pirenzepine Methoctramine & Triptramine Darifenacin
    • 5. Nicotinic (N) Receptors
      • Nicotinic receptors: nicotinic actions of ACh are those that can be reproduced by the injection of Nicotine (Nicotiana tabacum)
        • Can be blocked by tubocurarine and hexamethonium
      • ligand-gated ion channels
        • activation results in a rapid increase in cellular permeability to Na+ and Ca++ resulting - depolarization and initiation of action potential
    • 6. Sites of Cholinergic transmission and types of Receptors Site Types Selective agonist Selective antagonist All Postganglionic Parasympathetic Postganglionic sympathetic to sweat gland & BV Muscarinic Muscarine Atropine Ganglia (Both Para and sympathetic and also Adrenal Medulla N N DMPP Hexamethonium Skeletal Muscle N M PTMA Curare CNS Muscarinic Muscarine Oxotremorine Atropine
    • 7. Classification - Anticholinergics
      • Natural: Atropine and Hyoscine (scopolamine)
      • Semisynthetic derivtives: Homatropine, Atropine methonitrate, Hyoscine butylbromide, Ipratropium bromide, Tiotropium bromide
      • Synthetic Compounds:
        • Mydriatics: Cyclopentolate and Tropicamide
        • Vasicoselective: Oxybutynin, Flvoxate, Tolterodine
        • Antiprkinsonian: Trihexyphenidyl, Procyclidine, Biperiden
        • Antisecretory:
          • Quartenary ammonium compounds: Propantheline, Oxyphenonium, Clidinium, Glycopyrrolate, Isopropamide
          • Tertiary amines: Dicyclomine, Valethamate, Pirenzepine
    • 8. Atropine as Prototype
      • Atropine (hyoscyamine ) is found in the plant Atropa belladonna, or deadly nightshade
      • Also in Datura stramonium, also known as jimsonweed (Jamestown weed) or thorn apple
      • Scopolamine (hyoscine) occurs in Hyoscyamus niger
      • Many antihistaminics: Histamine, Serotonin, & Ergots alkaloids, Antipsychotic Agents & Lithium and antidepressant drugs have similar structures and, predictably, significant antimuscarinic effects
      Datura stramonium Atropa belladona
    • 9. Atropine - Chemically
      • Atropine: Ester of tropic acid (aromatic acid) + tropine
      • Scopolamine: Ester of tropic acid (aromatic acid) + scopine
      • Chemically tropine and scopine are closely similar
      • Most of the actions of both are similar
    • 10. Atropine - Mechanism
      • Atropine causes reversible (surmountable) blockade of cholinomimetic actions at muscarinic receptors
        • blockade by a small dose of atropine can be overcome by a larger concentration of acetylcholine or equivalent muscarinic agonist
      • Atropine is highly selective for muscarinic receptors
      • Does not distinguish between the M 1 , M 2 , and M 3
      • Some quaternary amine antimuscarinic agents have significant ganglion-blocking actions
    • 11. Atropine - Pharmacokinetics
      • Absorption:
        • The natural alkaloids and most tertiary antimuscarinic drugs are well absorbed from the gut and conjunctival membranes – some even over the skin (scopolamine)
        • Quaternary ones – only upto 30%
      • Distribution:
        • Atropine and the other tertiary agents are widely distributed in the body
        • Scopolamine is rapidly and fully distributed into the central nervous system where it has greater effects than most other antimuscarinic drugs
        • Quaternary derivatives are poorly taken up by the brain
      • Metabolism:
        • Atropine is metabolized in liver by conjugation and 60% excretes unchanged in urine
        • Effects disappear quickly within 2 Hrs except eye
    • 12. Pharmacological Effects - Atropine
      • Central Nervous System: Overall CNS stimulant
        • Atropine has only peripheral effects and minimal minimal stimulant effect on CNS – low entry
        • Atropine stimulates many medullary centres – vagal, respiratory and vasomotor
        • Depresses vestibular excitation – antimotion sickness property
        • Scopolamine has more marked central effects – amnesia and drowsiness
        • Parkinson's disease is reduced by centrally acting antimuscarinic drugs – acting on Basal ganglia (atropine)
      • Eye:
        • Topical atropine and other tertiary antimuscarinic drug - results in unopposed sympathetic dilator activity and mydriasis
        • Cycloplegia: desirable in Ophthalmology
          • but hazardous in narrow angle glaucoma
        • Dry Eye: Not desirable
    • 13. Paralysis of accommodations - Atropine
    • 14. Effect of Scopolamine
    • 15. Pharmacological Effects of Atropine – contd.
      • CVS:
        • Moderate and high doses: TACHYCARDIA
        • More In young adults - Because of Vagotonia
        • MOA: SAN, AVN are richly supplied by Parasympathetic Nerves
          • Atropine produces PS blockade in SAN – tachycardia
          • AVN – Atropine produces PS blockade – higher AV conduction rate (reduced PR interval in ECG)
        • IM/SC injection initially – transient BRADYCARDIA – may be due to inhibition of presynaptic M1 autoreceptor inhibition (not due to stimulation of vagal centre)
          • Evidenced by Pirenzepine injection does not cross BBB
        • BP: Parasympathetic nerve stimulation dilates coronary arteries, and sympathetic cholinergic nerves (predominant) cause vasodilatation in the skeletal muscle vascular bed - Atropine can block this vasodilatation
          • But, histamine release cause direct vasodilatation
        • However, No marked effect on BP
    • 16. Heart rate and salivary secretion after Atropine
    • 17. Pharmacological Effects of Atropine – contd.
      • Respiratory System:
        • Smooth muscles and secretor glands receive innervations from parasympathetic system
        • Bronchodilatation and reduction in secretion in asthma
        • Particularly used in COPD and prior to initiation of inhalation therapy in asthma
      • Sweat glands:
        • Suppresses thermoregulatory sweating – peripheral and central action
        • May cause "atropine fever“ - children
      • Urinary:
        • Slows voiding
        • Useful in spasm conditions – inflammation
        • Danger – Elderly (BHP)
    • 18. Pharmacological Effects of Atropine – contd.
      • GIT:
        • Decrease in GI motility
        • Gastric emptying time is prolonged, and intestinal transit time is lengthened
        • Dry mouth occurs frequently in patients taking antimuscarinic drugs
        • Gastric secretion is blocked with larger doses – blocks acid, pepsin and mucus secretion
        • Pirenzepine is more effective
    • 19. Various Effects of Atropine
    • 20. Anticholinergics - Ophthalmic uses
      • Mydriatic and Cycloplegic
      • Used as eye drop or ointment:
        • Diagnostic:
          • Atropine 1% ointment is used
            • Measurement of refractive error
            • Ophthalmic examination of retina - fundoscopy
            • Preferred ones: Homatropine, Tropicamide and cyclopentolate – shorter action
        • Therapeutic Uses:
          • For resting eye: Iritis, iridocyclitis, keratitis, corneal ulcer etc.
          • Alternating with miotics (prevention of synechia)
    • 21. Therapeutic Uses Anticholinergics
      • Antisecretory:
        • Preanaesthetic medication:
          • To reduce secretions
          • To prevent laryngospasm
        • Peptic ulcer
        • Pulmonary embolism
        • Hyperhidrosis
      • Antispasmodic:
        • Intestinal and renal colic – not in biliary colic
        • Diarrhoea (nervous and drug induced) – Lomotil
        • Pylorospasm, gastric hypermotility, gastritis, nervous dyspepsia etc.
    • 22. Uses Anticholinergics – contd.
        • Parkinsonism: Mild cases of parkinsonism (early cases), Drug induced Parkinsonism and adjunct to Levodopa
        • Motion sickness:
          • Hyoscine (scopolamine) is the drug used – Oral, injection and transdermal patch
          • 0.2 mg orally given as prophylaxis before journey
          • Not effective in other type of vomiting
        • Twilight sleep: sedation and amnesia
      • To antagonize Muscarinic effects of Drugs and Poisons: Anti-ChE, Mushroom poisoning, and to block Muscarinic effects of Neostigmine, Cobra envenometion
    • 23. Anticholinergics – uses
      • CVS:
        • Vagolytic - Marked reflex vagal discharge in myocardial infarction - depression of SA or AV node function to impair cardiac output - Parenteral atropine or a similar antimuscarinic drug
        • Hyperactive carotid sinus reflexes
      • Respiratory:
        • Ipratropium Bromide – in COPD and chronic bronchitis
          • Improves mucociliary clearance and bronchodilatation
    • 24. Anticholinergic - ADRs
      • Commonly occurring but of non serious type
      • Mydriasis and cycloplegia – using as antisecretory or Preanaesthetic medication
      • Poisoning:
        • Causes:
          • Drug overdose
          • Consumption of Belladona and Datura seeds
        • Symptoms:
          • Dry mouth, difficulty in swallowing and talking
          • Dry, flushed and hot skin, fever, decreased bowel sound, photophobia
          • Excitement, psychotic behavior, delirium and hallucinations
          • Hypotension and cardiovascular collapse
    • 25. Atropine Poisoning – contd.
      • Diagnosis: Methacholine 5 mg or Neostigmine 1 mg SC – no muscarinic effects
      • Treatment:
        • Gastric lavage in case of ingestion – KMNO4
        • Dark Room
        • Cold sponging and ice bags
        • Physostigmine 1–3 mg SC or IV
        • Maintenance of blood volume, assisted respiration and Diazepam to control convulsions
    • 26. Anticholinergic - Contraindications
      • Glaucoma – Narrow angle (Precipitation of angle closure)
      • BHP – urinary retention
      • Acid peptic ulcer diseases (Non-selective ones) – precipitation of symptoms
    • 27. Atropine Substitutes - Quarternary compounds
      • Incomplete Oral absorption, Poor penetration in Eye and CNS, Longer acting than Atropine, Higher Nicotinic Blocking Property, NM Blockade
      • Drugs:
        • Hyoscine Butylbromide: Oesophageal and GIT spastic conditions – Buscopan
        • Atropine methonitrate: Abdominal colics and hypercidity
        • Ipratropium Bromide: Selective action on Bronchial SM
          • Enhanced mucocilliary clearance (contrast to Atropine)
          • Slowly acting Bronchodilator - 1-2 Hrs (prophylactic use)
          • Acts mainly on larger Central airways (contrast to sympoathomimetics)
          • More effective in COPD than Asthma
          • Other Drugs – Tiotropium bromide, Propantheline, Oxyphenonium, Clidinium and Glycopyrrolate
    • 28. Tertiary Amines
      • Dicyclomine and valethamate
      • Dicyclomine: Direct SM relaxant and weak antispasmodic
        • Lesser side effects than Atropine
        • Atropine toxicity in infants (not recommended below 6 months)
      • Valethmate: Dilatation of Cervix in delayed labour
    • 29. Individual Drugs – Vasicoselective
      • Oxybutynin:
        • Specific selectivity for receptors in Urinary bladder and salivary gland (M1/M3)
        • Additional smooth muscle relaxation property
        • Uses:
          • Bladder surgery after urologic surgery
          • Spina bifida and nocturnal enuresis
          • Involuntary voiding in patients with neurologic disease - children with meningomyelocele
          • Dose: 5 mg BD/tds or local instillation
      • Tolterodine – M3 selective
      • Flavoxate – similar to Oxybutynin
      • Drotaverine: Newer Drug - Non anticholinergic smooth muscle relaxant – elevation of cAMP/cGMP
        • Renal colic, biliary colic, IBS, uterine spasms etc.
        • Dose: 40 – 80 mg tds
    • 30. Mydriatics
      • Homatropine, Cyclopentolate and Tropicamide – various ophthalmological procedures as substitutes of Atropine
    • 31. Drugs acting in Autonomic ganglia
      • Ganglion stimulants:
        • Selective agonists: Nicotine, Lobeline, DMPP and TMA
        • Non-selective: Acetylcholine, carbachol, Pilocarpine, Anticholinesterases
      • Ganglion Blockers:
        • Competitive blockers:
          • Quaternary compounds: Hexamethonium, Pentolinium
          • Secondary/tertiary: Mecamylamine, Pempidine
        • Persistent depolarizers: Nicotine (large dose) and Anticholinesterases
    • 32. Remember !!!
      • Atropine and its Pharmacological Effects
        • Therapeutic uses of Atropine
        • Mechanism of Mydriasis and Cycloplegia
      • Names of Atropine Substitutes with their Uses
        • Details of Atropine Substitutes – Ipratropium bromide
      • Treatment of Atropine Poisoning
      • Ganglion Stimulants and Blockers Drugs
    • 33. THANK YOU

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