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Cholinergic system model questions & answers

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Cholinergic system model questions & answers

  1. 1. [Cholinergic system]<br />Model Questions and answers<br /><br />
  2. 2. Q. Enumerate the different steps in cholinergic transmission, in the order of occurrence. Add a note on synthesis of acetylcholine in cholinergic nerve endings. 4 + 1<br />Cholinergic transmission<br />Impulse conduction<br />Arrival of impulse<br />Synthesis, Storage & release<br />of Ach by exocytosis<br />Combination of Ach<br />With receptors<br />Postjunctional activity: <br /><ul><li>Excitatory[EPSP] or
  3. 3. Inhibitory[IPSP]</li></ul>Termination of <br /> Ach action<br /> hydrolysis by true cholinesterase<br />Synthesis of ACH<br />ATP <br />+ Acetate <br />+ CoEn-A<br />Acetylcholine + CoEn-A<br />= Acetyl CoEn-A<br /> + [acetyl transferase]<br />Choline<br />
  4. 4. Q. Classify anti-cholinesterases with examples. Discuss the pharmacotherapy of organophosphorous poisoning. 3 + 2<br />Ans. CLASSIFICATION<br />Reversible anticholinesterases<br />CarbamatesAcridine<br />Tacrine.<br />Physostigmine<br />Neostigmine<br />Pyridostigmine<br />Edrophonium<br />Ambenonium<br />Demecarium<br />Rivastigmine, <br />Donepezil, <br />Galantamine.<br />Irreversible anticholinesterases<br />Organophosphates Carbamates<br />EchothiophateCarbaryl*<br />Parathion* Propoxur*<br />Malathion*<br />Diazinon*<br />Tabun#<br />Sarin#<br />Soman#<br />Ans. ‘PHARMACOTHERAPY’ OF OP POISONING<br /><ul><li>Termination of exposure-copious washing
  5. 5. Signs and symptoms are due to excess of cholinergic activity resulting in excess of parasympathetic or sympathetic activity.
  6. 6. Antimuscarinic drug Atropine is the specific antidote[DOC]
  7. 7. Atropine 2mg i.v, repeated every 10 minutes until atropinization symptoms appear.
  8. 8. Maintenance dose continued for 2 weeks
  9. 9. Pralidoxime, cholinesterase activator, is administered for nicotinic adverse effects, after atropine. 1-2g slow i.v.
  10. 10. Pralidoxime is C.I. in carbamate poisoning
  11. 11. Diazepami.v. if convulsions are present
  12. 12. Other supportive measures</li></li></ul><li>Q. Name six groups of drugs used in the treatment of glaucoma Explain the mechanism of action of latanoprost. 3+2<br />Prostaglandin analogues<br />Eg. Latanoprost<br />2. β Adrenergic blockers<br />Eg. Timolol<br />3. α Adrenergic agonists<br />Eg. Apraclonidine<br />4. Carbonic anhydrase inhibitors<br />Eg. Acetazolamide<br />5. Miotics<br />Eg. Pilocarpine<br />6. Mannitol<br />MOA of latanoprost<br /><ul><li>MOA- Increases permeability of tissues in ciliary muscles
  13. 13. Increases uveo-scleral outflow
  14. 14. May also increase trabecular out flow</li></li></ul><li>Ans. Mydriatic<br />α Adrenergic agonists -Eg. Phenylephrine<br />Antimuscarinics- Atropine, Homatropine, tropicamide, Cyclopentolate,<br />Anticholinesterases- Physostigmine<br />Ganglionic blockers- Eg. Hexamethonium<br />Uses <br />Facilitates fundus [eye] examination [Phenylephrine without cycloplegia]<br />Refraction testing [Antimuscarinics]<br />Alternatively with miotics to prevent formation of adhesions or to break-between iris and lens/cornea<br />To give rest to internal ocular muscles and as anodyne in inflammatory conditions of eye like iridocyclitis[ Atropine]<br />Q. Enumerate mydriatics. Discuss the uses of various mydriatics 2 + 3<br />
  15. 15. Q. Name two cholinesterases. Mention differences between them. 1 + 2<br />Ans.<br />Two cholinesterases<br />Acetyl cholinesterase[true] 2. Butyrylcholinesterase [pseudo]<br />Differences<br />
  16. 16. Write briefly on Edrophonium test. 3<br /> [Tensilon]Edrophonium test<br />To aid diagnosis<br />i.v.2 mg of edrophonium chloride->45 seconds -> 8 mg if the first dose is without effect ->Brief improvement in strength ->MG diagnosis<br />To moderate treatment in patient already being treated and c/o muscle weakness<br />i.v. 2 mg.<br />Decrease in strength indicates cholinergic crisis [Overdose of anticholinesterases in tt] <br />Improvement signifies myasthenic crisis [Under dose of anticholinesterases in tt]<br />
  17. 17. Q. Location of different subtypes of cholinoreceptors 2 <br />Ans<br /> <br />Location<br />Receptor<br />Gastric glands, Autonomic ganglia & CNS<br />M1<br />SA node, AV node, Atrium, Ventricle, Auto receptors <br />M2<br />Visceral smooth muscle, Iris, Ciliary muscle, Exocrine glands, Vascular endothelium.<br />M3<br />CNS<br />M4<br />M5<br />NM junction<br />NM<br />Autonomic ganglia, Adrenal medulla<br />NN<br />
  18. 18. Q. Why neostigmine is preferred over physostigmine in the treatment of myasthenia gravis? <br /> 2<br />Ans. <br />Unlike physostigmine<br />They have direct action on Nicotinic receptors at NM junction -Hence augmentation of action<br />Being quaternary compounds do not cross BBB –No CNS effects <br />
  19. 19. Q. Rationale for use of Timolol in glaucoma 3<br />Ans<br />It is a non-slectiveβ blocker.<br />It blocks the β2 receptors in ciliary body and reduces the secretion of aqueous humor.<br />Produce smooth and sustained fall in IOT<br />No change in pupil size as with pilocarpine.<br />Convenience of dosage-once or twice daily<br />Less adverse effects<br />It has systemic ADEs like worsening of bronchial asthma, CHF and bradycardia<br />
  20. 20. Q. Treatment of Atropine poisoning 2<br />Ans<br />Gastric lavage with KMNO4-if ingested<br />Nursed in a dark, quite room<br />Cold sponging<br />Physostigmine-1-3 mg i.v/s.c<br />General supportive measures[ i.v. fluids, diazepam, respiration]<br />
  21. 21. Q. Explain the actions of atropine on the eye and CNS. Explain the therapeutic uses of atropine substitutes 1+4<br />Ans<br />Atropine on eye-<br />It competitively blocks M3 receptors in constrictor pupillaeand ciliary muscle and effect passive mydriasis& Cycloplegia. It also increases IOT and abolishes light reflex.<br />Atropine on CNS<br />It crosses BBB. It is a CNS stimulant. Depresses vestibular system. Blocks cholinergic activity in basal ganglia and reduces tremor and rigidity in parkinsonism<br />High doses produce delirium and hallucinations.<br />……..See next slide for uses of atropine substitutes<br />
  22. 22. Q. Therapeutic uses of atropine substitutes<br />Ans<br />Motion sickness-Scopolamine<br />Mydriatics-Homatropine, tropicamide, cyclopentolate<br />Preanesthetic-Glycopyrrolate<br />Intestinal and renal colic-Dicyclomine<br />COPD, bronchial asthma-ipratropium & tiotropium bromide<br />Parkinsonism-trihexyphenydyl<br />Bradyarrhythmias-Atropine<br />
  23. 23. Q. Write briefly on cycloplegicmydriatics -3<br />Ans.<br />Cycloplegicmydriatics are the drugs which paralyze ciliary muscles and constrictor pupillae<br />Antimuscarinics like atrpoine competitively block M3 receptors in these sites and effect Cycloplegia, passive mydriasis and abolish light reflex<br />Eg. Atropine, homoatropine, tropicamide, cyclopentolate<br />Atropine is the longest acting[7days] & tropicamide is the shortest.<br />They are used for fundus examination, refractory testing , to give rest to muscles of eye and to break iris adhesions alternatively with miotics<br />
  24. 24. Q. Mention two drugs used in myesthenia gravis. How will you differentiate myastenic crisis from choloinergic crisis 1+4<br />Ans<br />Drugs in MG<br />Anticholinesterases-Eg. Neostigmine, Pyridostigmine<br />Glucocorticoids-Prednisolone<br />Immunosuppresants-Azathioprine, Cyclosporine<br />Cholinergic and myasthenic crisis<br />Differentiated by Edrophonium test<br />i.v.2 mg of edrophonium chloride-><br />Decrease in strength indicates cholinergic crisis [Overdose of anticholinesterases in tt] <br />Improvement signifies myasthenic crisis [Under dose of anticholinesterases in tt]<br />
  25. 25. Q. Mention any SIX drugs used in glaucoma. Explain the mechanism of action of any one drug 5<br />Drugs used in glaucoma<br />Pilocarpine<br />Timolol<br />Latanaprost<br />Acetazolamide<br />Apraclonidine<br />Mannitol<br /> MOA of α2 agonists<br />α 2 agonists primarily reduce secretion of aqueous humor by acting on the α 2 receptors on the ciliary body. Subsidiary action is their α 1action, constriction of ciliary blood vessels,reduction in the synthesis of aqueous humor <br />
  26. 26. Q. Uses and adverse effects of neuromuscular blockers 5<br />Uses<br />Ans.<br />Surgical relaxation[Adsjuant to GA]<br />Tracheal Intubation<br />Control of Ventilation-to reduce chest wall resistance in pts on ventilators<br />Treatment of Convulsions in epilepsy<br />SCH - brief procedures – endotracheal intubation, laryngoscopy, esophagoscopy, reduction of fractures and dislocations.<br />With ECT-to prevent convulsions & trauma<br />Adverse effects<br />Muscle Pain-Myalgias are a common postoperative complaint [SCh]<br />Respiratory paralysis<br />Flushing<br />Fall in BP[dtc]<br />Precipitation of asthma[dtc]<br />Malignant hyperthermia[SCh]<br />Increased Intraocular Pressure[SCh]<br />Increased Intragastric Pressure[SCh]<br />Hyperkalemia [SCh+burns etc.]<br />
  27. 27. Mention any SIX antimuscarinic agents Mention one use for each 5<br />Uses<br />Antimuscarinics<br />Atropine<br />Scopolamine<br />Homatropine<br />Glycopyrrolate<br />Benzhexol<br />Ipratropium bromide<br />OP poisoning<br />Travel sickness<br />Mydriatic for testing of errors of refraction<br />Preanesthetic-antisecretory<br />Parkinsonism<br />As bronchodilator in COPD & Bronchial asthma<br />
  28. 28. Q. List the differences between physostigmineand neostigmine- 2<br />
  29. 29. Q. Explain the pharmacological basis for the following. 2<br />2. Pyridostigmine is used in myasthenia gravis<br />1. Atropine is contraindicated in patients with Glaucoma<br />The intraocular tension tends to rise, especially in narrow angle glaucoma, as drainage of aqueous humor is compromised by crowding of the iris at angles<br />Pyridostigmine is a reversible anti cholinesterase<br />It inhibits the acetyl cholinesterase at neuromuscular junction and potentiates the action of Ach.<br />More acetylcholine is made available to stimulate the less than normal no. of nicotinic receptors in myasthenia gravis.<br />There by improves the muscle power, reduces fatigue.<br />It requires less frequent dosing compared to neostigmine<br />
  30. 30. Write briefly on ‘Succinylcholine’5<br />Chemistry: Resembles Ach, quaternary compound<br />MOA: It is a depolarizing neuromuscular blocker. Produces Phase I block by persistent depolarization of nicotinic receptor and phase II block by receptor desensitization. Duration is about five mts.<br />PK: Not absorbed orally nor crosses BBB. Hydrolyzed by pseudocholinesterase. Resistant to true cholinesterase.<br />ADEs: In those with variant pseudocholinesterase can produce succinylcholineapnoea.<br />Along with fluorinated anesthetics, in susceptible individuals can produce malignant hyperthermia.<br />Hyperkalaemiain those with trauma and burns<br />DIs: Should not be mixed with thiopentone in the same syringe<br />Uses:<br />1. Short procedures like endoscopies, <br />2. Fracture reduction<br />3. Tracheal intubation<br />
  31. 31. Q. Enumerate the types & subtypes of cholinergic receptors. Mention the sites where acetylcholine is theprincipal neurotransmitter. 2+2=4<br />Types & subtypes<br />Muscarinic<br />M1, M2, M3, M4, M5<br />Nicotinic<br />NN, NM<br />Cholinergic sites<br />M1: Autonomic Ganglia, Gastric glands, CNS<br />M2: SA node, AV node, atrium, ventricle, <br />M3: Visceral smooth muscle<br />Iris, ciliary muscles, exocrine glands, vascular endothelium<br />M4, M5 : CNS<br />NN :Autonomic ganglia & adrenal medulla<br />NM :Neuromuscular junction<br />
  32. 32. MCQ-1<br /> <br />Reactivation of cholinesterase enzyme inhibited by the following agent does not involve hydrolysis<br />A. Edrophonium C. Physostigmine<br />B. Galantamine D. Neostigmine<br />
  33. 33. MCQ<br /> <br />Anticholinergic which can be used to facilitate testing errors of refraction includes<br />Dicyclomine<br />Clidinium<br />Oxybutynin<br />Cyclopentolate<br />
  34. 34. MCQ<br /> <br />Miotics include<br />Anticholinesterases<br />α1 Adrenergic agonists<br />Ganglionic blockers <br />Antimuscarinics<br />
  35. 35. MCQ<br /> <br />Non-selective betablockers used in the pharmacotherapy of glaucoma includes<br />Betaxolol<br />Atenolol<br />Timolol<br />Esmolol<br />
  36. 36. MCQ<br />Preferred anticholinesterase used in the treatment of Belladona[Atropine] poisoning is<br />Physostigmine<br />Edrophonium<br />Neostigmine <br />Parathion<br />
  37. 37. MCQ<br />Phenylephrine instilled in eye produces:<br />Mydriasis but no cycloplegia.<br />Cycloplegia but no mydriasis<br />Both mydriasis and cycloplegia.<br />Neither mydriasis nor cycloplegia.<br />
  38. 38. MCQ<br />Following are the drugs instilled locally into the eye in glaucoma EXCEPT<br />Timolol<br />Dorzolamide<br />Acetazolamide<br />Dipivefrine<br />
  39. 39. MCQ<br />Following drugs can be used in organophosphorous poisoning EXCEPT<br />Prolidoxime<br />Atropine<br />Diazepam<br />Acetylcholine<br />
  40. 40. MCQ<br />Which of the following skeletal muscle relaxant is shortest acting<br />D-tubocuraine<br />Pancuronium<br />Cisatra curium<br />Succinyl choline<br />
  41. 41. The cholinomimetic drug which is not an alkaloid<br />Acetylcholine<br />Muscarine<br />Pilocarpine<br />Arecoline<br />
  42. 42. The antimuscarinic agent which has high affinity for receptors in urinary bladder and salivary gland<br />Oxybutynin<br />Ipratropium<br />Pirenzepine<br />Tropicamide<br />
  43. 43. Parasympathomimetics produce-<br />Miosis, bradycardia, bronchodilatation<br />Mydriasis, bradycardia, bronchoconstriction<br />Miosis, bradycardia, bronchoconstriction<br />Miosis, tachycardia, bronchoconstriction<br />
  44. 44. Neostigmine can be used in all the following conditions, except:<br />Cholinergic crisis<br />Myasthenia gravis<br />Paralytic ileus<br />Curare poisoning<br />
  45. 45. Pralidoxime is a<br />Non-selective muscarinic receptor blocker<br />Selective M1 receptor blocker<br />Cholinesterase enzyme reactivator<br />Cholinomimetic alkaloid <br />
  46. 46. Following are the drugs effective in glaucoma, EXCEPT <br />Dipivefrine<br />Pilocarpine<br />Timolol<br />Dopamine<br />
  47. 47. Ipratropium bromide inhalation is preferred over atropine as bronchodilator because<br />Does not affect the mucociliary secretion<br />Not absorbed when it is swallowed<br />Lack of CNS effects<br />All of the above<br />
  48. 48. In which condition atropine is contraindicated?<br />Heart block<br />Peptic ulcer<br />Hypertrophy of prostrate<br />Bronchial asthma<br />
  49. 49. Post operative muscle soreness may be a side effect of the following neuromuscular blocker<br />d-Tubocurarine<br />Succinylcholine<br />Pancuronium<br /> -Atracurium<br />
  50. 50. Which of the following drugs undergoes “Hoffmann” elimination.<br />Succinylcholine<br />Pancuronium<br />Vecuronium<br /> -Atracurium<br />
  51. 51. Pseudocholinesterase can metabolize the following drugs, EXCEPT<br /> <br />Succinylcholine<br />Procaine<br />Acetylcholine<br />Bethanechol<br />
  52. 52. Timolol reduces the intraocular pressure by<br />Reducing the aqueous humor secretion<br />Producing miosis<br />Producing mydriasis<br />Constricting the ciliary blood vessels <br />
  53. 53. The anticholinesterase agent not useful in Alzheimer’s disease<br />Rivastigmine<br />Donepezil<br />Pyridostigmine<br />Galantamine<br />
  54. 54. All of the following drugs are clinically used in myasthenia gravis EXCEPT<br />Neostigmine<br />Prednisolone<br />Pyridostigmine<br />Pilocarpine<br />
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