Anticholinergics - drdhriti
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Anticholinergics - drdhriti



A power point presentation on "anticholinergics" suitable for medical undergraduate MBBS level students of Pharmacology.;

A power point presentation on "anticholinergics" suitable for medical undergraduate MBBS level students of Pharmacology.;



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Anticholinergics - drdhriti Anticholinergics - drdhriti Presentation Transcript

  • Anticholinergic Drugs Department of Pharmacology NEIGRIHMS, Shillong
  • Introduction
    • 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
  • Classification
    • Natural: Atropine and Hyoscine (scopolamine)
    • Semisynthetic derivtives: Homatropine, Atropine methonitrate, Hyoscine butylbromide, Ipratropium bromide, Tiotropium bromide
    • Sythetic 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
  • Source and Chemistry
    • 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 antihistaminic: Histamine, Serotonin, & Ergots alkaloids, Antipsychotic Agents & Lithium and antidepressant drugs have similar structures and, predictably, significant antimuscarinic effects
    • Tertiary agents – Eye and CNS
    • Quartenary agents – More Peripheral effect
    Datura stramonium Atropa belladona
  • The Structure
  • 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
  • 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
    • Most synthetic antimuscarinic drugs are considerably less selective than atropine in interactions with nonmuscarinic receptors
    • Some quaternary amine antimuscarinic agents have significant ganglion-blocking actions
  • Pharmacological Effects - Atropine
    • Central Nervous System:
      • Atropine has 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
  • Paralysis of accommodations - Atropine
  • Effect of Scopolamine
  • Pharmacological Effects of Atropine – contd.
    • CVS:
      • SA node is very sensitive to muscarinic receptor blockade
      • Moderate to high dose of Atropine - blockade of vagal slowing and relative tachycardia
      • But lower doses - initial bradycardia before the effects of peripheral vagal block become manifested
      • Due to presynaptic muscarinic receptors on vagal postganglionic fibers that normally limit acetylcholine release in the sinus node and other tissues
      • However, no clinical significance – except in atrial flutter and fibrillation
      • Ventricles are less affected by antimuscarinic drugs
    • Blood Vessels:
      • 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
  • Heart rate and salivary secretion after Atropine
  • 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)
  • 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
  • Various Effects of Atropine
  • Therapeutic Uses Anticholinergics
    • Antisecretory:
      • Preanaesthetic medication:
        • To reduce secretions
        • To prevent laryngospasm
      • Peptic ulcer
      • Pulmonary embolism
    • Antispasmodic:
      • Intestinal and renal colic – not in biliary colic
      • Diarrhoea – Lomotil
    • Urinary: Reduction in urinary urgency in case of inflammatory diseases
  • Therapeutic Uses Anticholinergics
    • CNS Uses:
      • 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
  • 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
        • Tropicamide and cyclopentolate – shorter action
      • Therapeutic Uses:
        • For resting eye: Iritis, iridocyclitis, keratitis, corneal ulcer etc.
        • Alternating with miotics
  • 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
    • Hyperhidrosis
  • Anticholinergic - Contraindications
    • Glaucoma – Narrow angle (Precipitation of angle closure)
    • BHP – urinary retention
    • Acid peptic ulcer diseases (Non-selective ones) – precipitation of symptoms
  • 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
  • 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
  • Individual Drugs - Vasicoselective
    • Oxybutynin:
      • Specific selectivity for receptors in Urinary bladder and salivary gland
      • 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
    • 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
  • Drugs acting in Autonomic ganglia
    • Ganglion stimulants:
      • Selective agonists: Nicotine, Lobeline, DMPP TMA
      • Non-selective: Acetylcholine, carbcol, Pilocarpine, Anticholinesterases
    • Ganglion Blockers:
      • Competitive blockers:
        • Quaternary compounds: Hexmethonium, Pentolinium
        • Secondary/tertiary: Mecamylamine, Pempidine
      • Persistent depolarizers: Nicotine (large dose) and Anticholinesterases
  • Remember
    • Atropine and its substitutes
    • Pharmacological effects of Atropine
    • Mechanism of Mydriasis and Cycloplegia
    • Uses of different anticholinergic agents – vasicoselective and Ipratropium bromide
    • Treatment of Atropine Poisoning
    • Name of Ganglion blockers