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AAnnttiicchhoolliinneerrggiicc DDrruuggss 
Dr. D. K. Brahma 
Associate Professor 
Department of Pharmacology 
NEIGRIHMS, S...
 Parasympathetic Nervous System plays an important Role 
in physiologic and pathophysiologic responses - “Rest and 
Diges...
Recall - Muscarinic (M) and 
Nicotinic (N) Receptors: 
Muscarinic (M) - 
GPCR 
Nicotinic (N) – ligand 
gated
Muscarinic Receptor Subtypes: M1, M2, M3, 
M4 and M5 
M1 M2 M3 
Location Autonomic ganglia, 
Gastric glands and CNS 
Heart...
 Nicotinic receptors: nicotinic actions of ACh 
are those that can be reproduced by the 
injection of Nicotine (Nicotiana...
SSiitteess ooff CChhoolliinneerrggiicc ttrraannssmmiissssiioonn 
aanndd ttyyppeess ooff RReecceeppttoorrss 
Site Types Sel...
 Natural: Atropine and Hyoscine (scopolamine) 
 Semisynthetic derivtives: Homatropine, 
Atropine methonitrate, Hyoscine ...
 Atropine (hyoscyamine) is found in the plant Atropa 
belladonna, or deadly nightshade 
 Also in Datura stramonium, also...
 Atropine: Ester of tropic acid (aromatic acid) + 
tropine 
 Scopolamine: Ester of tropic acid (aromatic acid) + 
scopin...
Atropine causes reversible (surmountable) 
blockade of cholinomimetic actions at muscarinic 
receptors 
◦ blockade by a s...
 Absorption: 
◦ The natural alkaloids and most tertiary antimuscarinic drugs are well 
absorbed from the gut and conjunct...
 Central Nervous System: Overall CNS stimulant 
◦ Atropine has only peripheral effects and minimal minimal 
stimulant eff...
Paralysis of accommodations - 
Atropine
Effect of Scopolamine
 CVS: 
◦ Moderate and high doses: TACHYCARDIA 
◦ More In young adults - Because of Vagotonia 
◦ MOA: SAN, AVN are richly ...
HHeeaarrtt rraattee aanndd ssaalliivvaarryy sseeccrreettiioonn 
aafftteerr AAttrrooppiinnee
Respiratory System: 
◦ Smooth muscles and secretor glands receive 
innervations from parasympathetic system 
◦ Bronchodil...
GIT: 
◦ Decrease in GI motility 
◦ Gastric emptying time is prolonged, and 
intestinal transit time is lengthened 
◦ Dry ...
Various Effects of Atropine
Mydriatic and Cycloplegic 
Used as eye drop or ointment: 
◦ Diagnostic: 
 Atropine 1% ointment is used 
◦ Measurement o...
 Antisecretory: 
1. Preanaesthetic medication: 
 To reduce secretions 
 To prevent laryngospasm 
1. Peptic ulcer 
2. Pu...
◦ Parkinsonism: Mild cases of parkinsonism 
(early cases), Drug induced Parkinsonism and 
adjunct to Levodopa 
◦ Motion si...
CCVVSS:: 
◦ Vagolytic - Marked reflex vagal discharge in myocardial 
infarction - depression of SA or AV node function to...
Commonly occurring but of non serious type 
Mydriasis and cycloplegia – using as 
antisecretory or Preanaesthetic medica...
Diagnosis: Methacholine 5 mg or 
Neostigmine 1 mg SC – no muscarinic 
effects 
Treatment: 
◦ Gastric lavage in case of i...
Glaucoma – Narrow angle (Precipitation 
of angle closure) 
BHP – urinary retention 
Acid peptic ulcer diseases (Non-sel...
 Incomplete Oral absorption, Poor penetration in Eye and 
CNS, Longer acting than Atropine, Higher Nicotinic Blocking 
Pr...
 Dicyclomine and valethamate 
 Dicyclomine: Direct SM relaxant and weak antispasmodic 
◦ Lesser side effects than Atropi...
 Oxybutynin: 
◦ Specific selectivity for receptors in Urinary bladder and salivary 
gland (M1/M3) 
◦ Additional smooth mu...
MMyyddrriiaattiiccss 
Homatropine, 
Cyclopentolate and 
Tropicamide – 
various 
ophthalmological 
procedures as 
substitut...
Ganglion stimulants: 
◦ Selective agonists: Nicotine, Lobeline, DMPP and TMA 
◦ Non-selective: Acetylcholine, carbachol, ...
Atropine and its Pharmacological Effects 
◦ Therapeutic uses of Atropine 
◦ Mechanism of Mydriasis and Cycloplegia 
Name...
THANK YOU
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Anticholinergics - drdhriti

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  • Phenyl trimethyl ammonium
  • Transcript of "Anticholinergics - drdhriti"

    1. 1. AAnnttiicchhoolliinneerrggiicc DDrruuggss Dr. D. K. Brahma Associate Professor Department of Pharmacology NEIGRIHMS, Shillong
    2. 2.  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 IInnttrroodduuccttiioonn
    3. 3. Recall - Muscarinic (M) and Nicotinic (N) Receptors: Muscarinic (M) - GPCR Nicotinic (N) – ligand gated
    4. 4. Muscarinic Receptor Subtypes: M1, M2, M3, M4 and M5 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 Agonists Oxotremorine and MCN vasodilatation and MCN-343A Methacholine Bethanechol Antagonis ts Pirenzepine Methoctramine & Triptramine Darifenacin
    5. 5.  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 NNiiccoottiinniicc ((NN)) RReecceeppttoorrss
    6. 6. SSiitteess ooff CChhoolliinneerrggiicc ttrraannssmmiissssiioonn aanndd ttyyppeess ooff RReecceeppttoorrss Site Types Selective agonist Selective antagonist All Postganglionic Parasympathetic Postganglionic sympathetic to sweat gland & BV Muscarini c Muscarine Atropine Ganglia (Both Para and sympathetic and also Adrenal Medulla NN DMPP Hexamethoniu m Skeletal Muscle NM PTMA Curare CNS Muscarini c Muscarine Oxotremori ne Atropine
    7. 7.  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 CCllaassssiiffiiccaattiioonn -- AAnnttiicchhoolliinneerrggiiccss
    8. 8.  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 AAttrrooppiinnee aass PPrroottoottyyppee
    9. 9.  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 AAttrrooppiinnee -- CChheemmiiccaallllyy
    10. 10. 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 M1, M2, and M3 Some quaternary amine antimuscarinic agents have significant ganglion-blocking actions AAttrrooppiinnee -- MMeecchhaanniissmm
    11. 11.  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 AAttrrooppiinnee -- PPhhaarrmmaaccookkiinneettiiccss
    12. 12.  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 Pharmacological EEffffeeccttss -- AAttrrooppiinnee
    13. 13. Paralysis of accommodations - Atropine
    14. 14. Effect of Scopolamine
    15. 15.  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 PPhhaarrmmaaccoollooggiiccaall EEffffeeccttss ooff AAttrrooppiinnee –– ccoonnttdd..
    16. 16. HHeeaarrtt rraattee aanndd ssaalliivvaarryy sseeccrreettiioonn aafftteerr AAttrrooppiinnee
    17. 17. 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) PPhhaarrmmaaccoollooggiiccaall EEffffeeccttss ooff AAttrrooppiinnee –– ccoonnttdd..
    18. 18. 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 PPhhaarrmmaaccoollooggiiccaall EEffffeeccttss ooff AAttrrooppiinnee –– ccoonnttdd..
    19. 19. Various Effects of Atropine
    20. 20. 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) AAnnttiicchhoolliinneerrggiiccss -- OOpphhtthhaallmmiicc uusseess
    21. 21.  Antisecretory: 1. Preanaesthetic medication:  To reduce secretions  To prevent laryngospasm 1. Peptic ulcer 2. Pulmonary embolism 3. Hyperhidrosis  Antispasmodic: ◦ Intestinal and renal colic – not in biliary colic ◦ Diarrhoea (nervous and drug induced) – Lomotil ◦ Pylorospasm, gastric hypermotility, gastritis, nervous dyspepsia etc. TThheerraappeeuuttiicc UUsseess AAnnttiicchhoolliinneerrggiiccss
    22. 22. ◦ 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 UUsseess AAnnttiicchhoolliinneerrggiiccss –– ccoonnttdd..
    23. 23. CCVVSS:: ◦ 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 AAnnttiicchhoolliinneerrggiiccss –– uusseess
    24. 24. 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 AAnnttiicchhoolliinneerrggiicc -- AADDRRss
    25. 25. 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 Atropine Poisoning – contd.
    26. 26. Glaucoma – Narrow angle (Precipitation of angle closure) BHP – urinary retention Acid peptic ulcer diseases (Non-selective ones) – precipitation of symptoms Anticholinergic -- CCoonnttrraaiinnddiiccaattiioonnss
    27. 27.  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 Atropine SSuubbssttiittuutteess -- QQuuaarrtteerrnnaarryy ccoommppoouunnddss
    28. 28.  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 TTeerrttiiaarryy AAmmiinneess
    29. 29.  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 Individual Drugs – Vasicoselective
    30. 30. MMyyddrriiaattiiccss Homatropine, Cyclopentolate and Tropicamide – various ophthalmological procedures as substitutes of Atropine
    31. 31. 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 Drugs acting in Autonomic ganglia
    32. 32. 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 Remember !!!
    33. 33. THANK YOU
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