Cholinergic system model questions & answers

[Cholinergic system]Model Questions and answersDr.U.P.RathnakarMD.DIH.PGDHMwww.scribd.com

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 + 1Cholinergic transmissionImpulse conductionArrival of impulseSynthesis, Storage & releaseof Ach by exocytosisCombination of AchWith receptorsPostjunctional activity: Excitatory[EPSP] or

Inhibitory[IPSP]Termination of Ach action hydrolysis by true cholinesteraseSynthesis of ACHATP + Acetate + CoEn-AAcetylcholine + CoEn-A= Acetyl CoEn-A + [acetyl transferase]Choline

Q. Classify anti-cholinesterases with examples. Discuss the pharmacotherapy of organophosphorous poisoning. 3 + 2Ans. CLASSIFICATIONReversible anticholinesterasesCarbamatesAcridineTacrine.PhysostigmineNeostigminePyridostigmineEdrophoniumAmbenoniumDemecariumRivastigmine, Donepezil, Galantamine.Irreversible anticholinesterasesOrganophosphates CarbamatesEchothiophateCarbaryl*Parathion* Propoxur*Malathion*Diazinon*Tabun#Sarin#Soman#Ans. ‘PHARMACOTHERAPY’ OF OP POISONINGTermination of exposure-copious washing

Signs and symptoms are due to excess of cholinergic activity resulting in excess of parasympathetic or sympathetic activity.

Antimuscarinic drug Atropine is the specific antidote[DOC]

Atropine 2mg i.v, repeated every 10 minutes until atropinization symptoms appear.

Maintenance dose continued for 2 weeks

Pralidoxime, cholinesterase activator, is administered for nicotinic adverse effects, after atropine. 1-2g slow i.v.

Pralidoxime is C.I. in carbamate poisoning

Diazepami.v. if convulsions are present

Other supportive measuresQ. Name six groups of drugs used in the treatment of glaucoma Explain the mechanism of action of latanoprost. 3+2Prostaglandin analoguesEg. Latanoprost2. β Adrenergic blockersEg. Timolol3. α Adrenergic agonistsEg. Apraclonidine4. Carbonic anhydrase inhibitorsEg. Acetazolamide5. MioticsEg. Pilocarpine6. MannitolMOA of latanoprostMOA- Increases permeability of tissues in ciliary muscles

Increases uveo-scleral outflow

May also increase trabecular out flowAns. Mydriaticα Adrenergic agonists -Eg. PhenylephrineAntimuscarinics- Atropine, Homatropine, tropicamide, Cyclopentolate,Anticholinesterases- PhysostigmineGanglionic blockers- Eg. HexamethoniumUses Facilitates fundus [eye] examination [Phenylephrine without cycloplegia]Refraction testing [Antimuscarinics]Alternatively with miotics to prevent formation of adhesions or to break-between iris and lens/corneaTo give rest to internal ocular muscles and as anodyne in inflammatory conditions of eye like iridocyclitis[ Atropine]Q. Enumerate mydriatics. Discuss the uses of various mydriatics 2 + 3

Q. Name two cholinesterases. Mention differences between them. 1 + 2Ans.Two cholinesterasesAcetyl cholinesterase[true] 2. Butyrylcholinesterase [pseudo]Differences

Write briefly on Edrophonium test. 3 [Tensilon]Edrophonium testTo aid diagnosisi.v.2 mg of edrophonium chloride->45 seconds -> 8 mg if the first dose is without effect ->Brief improvement in strength ->MG diagnosisTo moderate treatment in patient already being treated and c/o muscle weaknessi.v. 2 mg.Decrease in strength indicates cholinergic crisis [Overdose of anticholinesterases in tt] Improvement signifies myasthenic crisis [Under dose of anticholinesterases in tt]

Q. Location of different subtypes of cholinoreceptors 2 Ans LocationReceptorGastric glands, Autonomic ganglia & CNSM1SA node, AV node, Atrium, Ventricle, Auto receptors M2Visceral smooth muscle, Iris, Ciliary muscle, Exocrine glands, Vascular endothelium.M3CNSM4M5NM junctionNMAutonomic ganglia, Adrenal medullaNN

Q. Why neostigmine is preferred over physostigmine in the treatment of myasthenia gravis? 2Ans. Unlike physostigmineThey have direct action on Nicotinic receptors at NM junction -Hence augmentation of actionBeing quaternary compounds do not cross BBB –No CNS effects

Q. Rationale for use of Timolol in glaucoma 3AnsIt is a non-slectiveβ blocker.It blocks the β2 receptors in ciliary body and reduces the secretion of aqueous humor.Produce smooth and sustained fall in IOTNo change in pupil size as with pilocarpine.Convenience of dosage-once or twice dailyLess adverse effectsIt has systemic ADEs like worsening of bronchial asthma, CHF and bradycardia

Q. Treatment of Atropine poisoning 2AnsGastric lavage with KMNO4-if ingestedNursed in a dark, quite roomCold spongingPhysostigmine-1-3 mg i.v/s.cGeneral supportive measures[ i.v. fluids, diazepam, respiration]

Q. Explain the actions of atropine on the eye and CNS. Explain the therapeutic uses of atropine substitutes 1+4AnsAtropine on eye-It competitively blocks M3 receptors in constrictor pupillaeand ciliary muscle and effect passive mydriasis& Cycloplegia. It also increases IOT and abolishes light reflex.Atropine on CNSIt crosses BBB. It is a CNS stimulant. Depresses vestibular system. Blocks cholinergic activity in basal ganglia and reduces tremor and rigidity in parkinsonismHigh doses produce delirium and hallucinations.……..See next slide for uses of atropine substitutes

Q. Therapeutic uses of atropine substitutesAnsMotion sickness-ScopolamineMydriatics-Homatropine, tropicamide, cyclopentolatePreanesthetic-GlycopyrrolateIntestinal and renal colic-DicyclomineCOPD, bronchial asthma-ipratropium & tiotropium bromideParkinsonism-trihexyphenydylBradyarrhythmias-Atropine

Q. Write briefly on cycloplegicmydriatics -3Ans.Cycloplegicmydriatics are the drugs which paralyze ciliary muscles and constrictor pupillaeAntimuscarinics like atrpoine competitively block M3 receptors in these sites and effect Cycloplegia, passive mydriasis and abolish light reflexEg. Atropine, homoatropine, tropicamide, cyclopentolateAtropine is the longest acting[7days] & tropicamide is the shortest.They are used for fundus examination, refractory testing , to give rest to muscles of eye and to break iris adhesions alternatively with miotics

Q. Mention two drugs used in myesthenia gravis. How will you differentiate myastenic crisis from choloinergic crisis 1+4AnsDrugs in MGAnticholinesterases-Eg. Neostigmine, PyridostigmineGlucocorticoids-PrednisoloneImmunosuppresants-Azathioprine, CyclosporineCholinergic and myasthenic crisisDifferentiated by Edrophonium testi.v.2 mg of edrophonium chloride->Decrease in strength indicates cholinergic crisis [Overdose of anticholinesterases in tt] Improvement signifies myasthenic crisis [Under dose of anticholinesterases in tt]

Q. Mention any SIX drugs used in glaucoma. Explain the mechanism of action of any one drug 5Drugs used in glaucomaPilocarpineTimololLatanaprostAcetazolamideApraclonidineMannitol MOA of α2 agonistsα 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

Q. Uses and adverse effects of neuromuscular blockers 5UsesAns.Surgical relaxation[Adsjuant to GA]Tracheal IntubationControl of Ventilation-to reduce chest wall resistance in pts on ventilatorsTreatment of Convulsions in epilepsySCH - brief procedures – endotracheal intubation, laryngoscopy, esophagoscopy, reduction of fractures and dislocations.With ECT-to prevent convulsions & traumaAdverse effectsMuscle Pain-Myalgias are a common postoperative complaint [SCh]Respiratory paralysisFlushingFall in BP[dtc]Precipitation of asthma[dtc]Malignant hyperthermia[SCh]Increased Intraocular Pressure[SCh]Increased Intragastric Pressure[SCh]Hyperkalemia [SCh+burns etc.]

Mention any SIX antimuscarinic agents Mention one use for each 5UsesAntimuscarinicsAtropineScopolamineHomatropineGlycopyrrolateBenzhexolIpratropium bromideOP poisoningTravel sicknessMydriatic for testing of errors of refractionPreanesthetic-antisecretoryParkinsonismAs bronchodilator in COPD & Bronchial asthma

Q. List the differences between physostigmineand neostigmine- 2

Q. Explain the pharmacological basis for the following. 22. Pyridostigmine is used in myasthenia gravis1. Atropine is contraindicated in patients with GlaucomaThe intraocular tension tends to rise, especially in narrow angle glaucoma, as drainage of aqueous humor is compromised by crowding of the iris at anglesPyridostigmine is a reversible anti cholinesteraseIt inhibits the acetyl cholinesterase at neuromuscular junction and potentiates the action of Ach.More acetylcholine is made available to stimulate the less than normal no. of nicotinic receptors in myasthenia gravis.There by improves the muscle power, reduces fatigue.It requires less frequent dosing compared to neostigmine

Write briefly on ‘Succinylcholine’5Chemistry: Resembles Ach, quaternary compoundMOA: 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.PK: Not absorbed orally nor crosses BBB. Hydrolyzed by pseudocholinesterase. Resistant to true cholinesterase.ADEs: In those with variant pseudocholinesterase can produce succinylcholineapnoea.Along with fluorinated anesthetics, in susceptible individuals can produce malignant hyperthermia.Hyperkalaemiain those with trauma and burnsDIs: Should not be mixed with thiopentone in the same syringeUses:1. Short procedures like endoscopies, 2. Fracture reduction3. Tracheal intubation

Q. Enumerate the types & subtypes of cholinergic receptors. Mention the sites where acetylcholine is theprincipal neurotransmitter. 2+2=4Types & subtypesMuscarinicM1, M2, M3, M4, M5NicotinicNN, NMCholinergic sitesM1: Autonomic Ganglia, Gastric glands, CNSM2: SA node, AV node, atrium, ventricle, M3: Visceral smooth muscleIris, ciliary muscles, exocrine glands, vascular endotheliumM4, M5 : CNSNN :Autonomic ganglia & adrenal medullaNM :Neuromuscular junction

MCQ-1 Reactivation of cholinesterase enzyme inhibited by the following agent does not involve hydrolysisA. Edrophonium C. PhysostigmineB. Galantamine D. Neostigmine

MCQ Anticholinergic which can be used to facilitate testing errors of refraction includesDicyclomineClidiniumOxybutyninCyclopentolate

MCQ Miotics includeAnticholinesterasesα1 Adrenergic agonistsGanglionic blockers Antimuscarinics

MCQ Non-selective betablockers used in the pharmacotherapy of glaucoma includesBetaxololAtenololTimololEsmolol

MCQPreferred anticholinesterase used in the treatment of Belladona[Atropine] poisoning isPhysostigmineEdrophoniumNeostigmine Parathion

MCQPhenylephrine instilled in eye produces:Mydriasis but no cycloplegia.Cycloplegia but no mydriasisBoth mydriasis and cycloplegia.Neither mydriasis nor cycloplegia.

MCQFollowing are the drugs instilled locally into the eye in glaucoma EXCEPTTimololDorzolamideAcetazolamideDipivefrine

MCQFollowing drugs can be used in organophosphorous poisoning EXCEPTProlidoximeAtropineDiazepamAcetylcholine

MCQWhich of the following skeletal muscle relaxant is shortest actingD-tubocurainePancuroniumCisatra curiumSuccinyl choline

The cholinomimetic drug which is not an alkaloidAcetylcholineMuscarinePilocarpineArecoline

The antimuscarinic agent which has high affinity for receptors in urinary bladder and salivary glandOxybutyninIpratropiumPirenzepineTropicamide

Parasympathomimetics produce-Miosis, bradycardia, bronchodilatationMydriasis, bradycardia, bronchoconstrictionMiosis, bradycardia, bronchoconstrictionMiosis, tachycardia, bronchoconstriction

Neostigmine can be used in all the following conditions, except:Cholinergic crisisMyasthenia gravisParalytic ileusCurare poisoning

Pralidoxime is aNon-selective muscarinic receptor blockerSelective M1 receptor blockerCholinesterase enzyme reactivatorCholinomimetic alkaloid

Cholinergic system model questions & answers

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Cholinergic system model questions & answers