Dr.U.P.RathnakarMD.DIH.PGDHM

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[Cholinergic system]Model Questions and

answers

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

Cholinergic transmission– Impulse conduction

– Arrival of impulse

– Synthesis, Storage & releaseof Ach by exocytosis

– Combination of Ach– With receptors

– Postjunctional activity: Excitatory[EPSP] or Inhibitory[IPSP]

– Termination of Ach action hydrolysis by true cholinesterase

Synthesis of ACH

ATP + Acetate + CoEn-A

= Acetyl CoEn-A

+ [acetyl transferase] Choline

Acetylcholine + CoEn-A

Q. Classify anti-cholinesterases with examples. Discuss the pharmacotherapy of organophosphorous poisoning.

3 + 2Ans. CLASSIFICATION

Reversible anticholinesterases Carbamates Acridine

Tacrine.• Physostigmine• Neostigmine• Pyridostigmine• Edrophonium• Ambenonium• Demecarium• Rivastigmine, • Donepezil, • Galantamine. Irreversible anticholinesterases Organophosphates

Carbamates • Echothiophate Carbaryl*• Parathion* Propoxur*• Malathion*• Diazinon*• Tabun#• Sarin#• Soman#

Ans. ‘PHARMACOTHERAPY’ OF OP POISONING

• Termination 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• Diazepam i.v. if convulsions are present• Other supportive measures

Q. Name six groups of drugs used in the treatment of glaucoma

Explain the mechanism of action of latanoprost. 3+2

1. Prostaglandin analoguesEg. Latanoprost2. β Adrenergic blockersEg. Timolol3. α Adrenergic agonistsEg. Apraclonidine4. Carbonic anhydrase inhibitorsEg. Acetazolamide5. MioticsEg. Pilocarpine6. Mannitol

MOA of latanoprosto MOA- Increases permeability of

tissues in ciliary muscles• Increases uveo-scleral outflow• May also increase trabecular out

flow

Ans. Mydriatic1. α Adrenergic agonists -Eg. Phenylephrine2. Antimuscarinics- Atropine, Homatropine, tropicamide, Cyclopentolate,3. Anticholinesterases- Physostigmine4. Ganglionic blockers- Eg. Hexamethonium

Uses 5. Facilitates fundus [eye] examination [Phenylephrine without cycloplegia]6. Refraction testing [Antimuscarinics]7. Alternatively with miotics to prevent formation of adhesions or to break-between

iris and lens/cornea8. To 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 + 2

Ans.Two cholinesterases

1. Acetyl cholinesterase[true] 2. Butyrylcholinesterase [pseudo] Differences

Parameters True PseudoDistribution Cholinergic sites

RBC, gray matterPlasma, Liver, intestine, white matter

Effect on ACh Very fast Slow

Inhibition Sensitive to Physostigmine

Sensitive to OPs

Function Termination of Ach action

Hydrolysis of ingested esters

Succinylcholine No effect Hydrolysis

Write briefly on Edrophonium test. 3

 [Tensilon]Edrophonium testTo aid diagnosis• i.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 weakness• i.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

 

Gastric glands, Autonomic ganglia & CNS

SA node, AV node, Atrium, Ventricle, Auto receptors

Visceral smooth muscle,

Iris, Ciliary muscle, Exocrine glands,

Vascular endothelium.

CNS

NM junctionAutonomic ganglia,

Adrenal medulla

LocationM1

M2

M3

M4

M5

NM

NN

Receptor

Q. Why neostigmine is preferred over physostigmine in the treatment of myasthenia gravis?

2

Ans.

Unlike physostigmine1. They have direct action on Nicotinic receptors at

NM junction -Hence augmentation of action2. Being quaternary compounds do not cross BBB –

No CNS effects

Q. Rationale for use of Timolol in glaucoma 3

• Ans• It is a non-slective β blocker.• It blocks the β2 receptors in ciliary body and reduces

the secretion of aqueous humor.• Produce smooth and sustained fall in IOT• No change in pupil size as with pilocarpine.• Convenience of dosage-once or twice daily• Less adverse effects• It has systemic ADEs like worsening of bronchial

asthma, CHF and bradycardia

Q. Treatment of Atropine poisoning 2

• Ans• Gastric lavage with KMNO4-if ingested• Nursed in a dark, quite room• Cold sponging• Physostigmine-1-3 mg i.v/s.c• General 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+4

• Ans• Atropine on eye-• It competitively blocks M3 receptors in constrictor pupillae and ciliary

muscle and effect passive mydriasis & Cycloplegia. It also increases IOT and abolishes light reflex.

• Atropine on CNS• It crosses BBB. It is a CNS stimulant. Depresses vestibular system.

Blocks cholinergic activity in basal ganglia and reduces tremor and rigidity in parkinsonism

• High doses produce delirium and hallucinations.

……..See next slide for uses of atropine substitutes

Q. Therapeutic uses of atropine substitutes

• Ans• Motion sickness-Scopolamine• Mydriatics-Homatropine, tropicamide, cyclopentolate• Preanesthetic-Glycopyrrolate• Intestinal and renal colic-Dicyclomine• COPD, bronchial asthma-ipratropium & tiotropium

bromide• Parkinsonism-trihexyphenydyl• Bradyarrhythmias-Atropine

Q. Write briefly on cycloplegic mydriatics -3

• Ans.• Cycloplegic mydriatics are the drugs which paralyze ciliary

muscles and constrictor pupillae• Antimuscarinics like atrpoine competitively block M3

receptors in these sites and effect Cycloplegia, passive mydriasis and abolish light reflex

• Eg. Atropine, homoatropine, tropicamide, cyclopentolate• Atropine 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+4

• Ans• Drugs in MG

• Anticholinesterases-Eg. Neostigmine, Pyridostigmine• Glucocorticoids-Prednisolone• Immunosuppresants-Azathioprine, Cyclosporine

• Cholinergic and myasthenic crisis• Differentiated by Edrophonium test• i.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 5

Drugs used in glaucoma

1. Pilocarpine2. Timolol3. Latanaprost4. Acetazolamide5. Apraclonidine6. Mannitol

MOA of α2 agonists

• 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

Q. Uses and adverse effects of neuromuscular blockers 5

Uses• Surgical relaxation[Adsjuant to

GA]• Tracheal Intubation• Control of Ventilation-to reduce

chest wall resistance in pts on ventilators

• Treatment of Convulsions in epilepsy

• SCH - brief procedures – endotracheal intubation, laryngoscopy, esophagoscopy, reduction of fractures and dislocations.

• With ECT-to prevent convulsions & trauma

Adverse effects• Muscle Pain-Myalgias are a

common postoperative complaint [SCh]

• Respiratory paralysis• Flushing• Fall in BP[dtc]• Precipitation of asthma[dtc]• Malignant hyperthermia[SCh]• Increased Intraocular

Pressure[SCh]• Increased Intragastric

Pressure[SCh]• Hyperkalemia [SCh+burns etc.]

Ans.

Mention any SIX antimuscarinic agents Mention one use for each 5

1. Atropine2. Scopolamine3. Homatropine

4. Glycopyrrolate

5. Benzhexol6. Ipratropium

bromide

1. OP poisoning2. Travel sickness3. Mydriatic for testing of

errors of refraction4. Preanesthetic-

antisecretory5. Parkinsonism6. As bronchodilator in

COPD & Bronchial asthma

Antimuscarinics Uses

Q. List the differences between physostigmine and neostigmine- 2

Q. Explain the pharmacological basis for the following. 2

1. Atropine is contraindicated in patients with Glaucoma• 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

2. Pyridostigmine is used in myasthenia gravis• Pyridostigmine is a reversible anti

cholinesterase• It 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’ 5• Chemistry: Resembles Ach,

quaternary compound• 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.

• PK: Not absorbed orally nor crosses BBB. Hydrolyzed by pseudocholinesterase. Resistant to true cholinesterase.

• ADEs: In those with variant pseudocholinesterase can produce succinylcholine apnoea.

• Along with fluorinated anesthetics, in susceptible individuals can produce malignant hyperthermia.

• Hyperkalaemia in those with trauma and burns

• DIs: Should not be mixed with thiopentone in the same syringe

• Uses:• 1. Short procedures like

endoscopies, • 2. Fracture reduction• 3. Tracheal intubation

Q. Enumerate the types & subtypes of cholinergic receptors. Mention the sites where acetylcholine is the principal neurotransmitter. 2+2=4

Types & subtypes• Muscarinic

• M1, M2, M3, M4, M5

• Nicotinic• NN, NM

Cholinergic sites• M1: Autonomic Ganglia, Gastric

glands, CNS• M2: SA node, AV node, atrium,

ventricle, • M3: Visceral smooth muscleIris, ciliary muscles, exocrine

glands, vascular endothelium• M4, M5 : CNS• NN :Autonomic ganglia &

adrenal medulla• NM :Neuromuscular junction

MCQ-1

 • Reactivation of cholinesterase enzyme

inhibited by the following agent does not involve hydrolysis

A. Edrophonium C. Physostigmine

B. Galantamine D. Neostigmine

MCQ

 • Anticholinergic which can be used to facilitate

testing errors of refraction includesA. DicyclomineB. ClidiniumC. OxybutyninD. Cyclopentolate

MCQ

 • Miotics includeA. AnticholinesterasesB. α1 Adrenergic agonistsC. Ganglionic blockersD. Antimuscarinics

MCQ

 • Non-selective betablockers used in the

pharmacotherapy of glaucoma includesA. Betaxolol B. AtenololC. TimololD. Esmolol

MCQ

• Preferred anticholinesterase used in the treatment of Belladona[Atropine] poisoning is

• Physostigmine• Edrophonium• Neostigmine• Parathion

MCQ

• Phenylephrine instilled in eye produces:– Mydriasis but no cycloplegia.– Cycloplegia but no mydriasis– Both mydriasis and cycloplegia.– Neither mydriasis nor cycloplegia.

MCQ

Following are the drugs instilled locally into the eye in glaucoma EXCEPT

• Timolol• Dorzolamide• Acetazolamide• Dipivefrine

MCQ

Following drugs can be used in organophosphorous poisoning EXCEPT

• Prolidoxime• Atropine• Diazepam• Acetylcholine

MCQ

• Which of the following skeletal muscle relaxant is shortest acting

• D-tubocuraine • Pancuronium• Cisatra curium• Succinyl choline

The cholinomimetic drug which is not an alkaloid

• Acetylcholine• Muscarine• Pilocarpine• Arecoline

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

• Oxybutynin• Ipratropium• Pirenzepine• Tropicamide

Parasympathomimetics produce-• Miosis, bradycardia, bronchodilatation• Mydriasis, bradycardia, bronchoconstriction• Miosis, bradycardia, bronchoconstriction• Miosis, tachycardia, bronchoconstriction

Neostigmine can be used in all the following conditions, except:

• Cholinergic crisis• Myasthenia gravis• Paralytic ileus• Curare poisoning

Pralidoxime is a• Non-selective muscarinic receptor blocker• Selective M1 receptor blocker• Cholinesterase enzyme reactivator• Cholinomimetic alkaloid

Following are the drugs effective in glaucoma, EXCEPT

• Dipivefrine• Pilocarpine• Timolol• Dopamine

Ipratropium bromide inhalation is preferred over atropine as bronchodilator because

• Does not affect the mucociliary secretion• Not absorbed when it is swallowed• Lack of CNS effects• All of the above

In which condition atropine is contraindicated?• Heart block• Peptic ulcer• Hypertrophy of prostrate• Bronchial asthma

Post operative muscle soreness may be a side effect of the following neuromuscular blocker– d-Tubocurarine – Succinyl choline– Pancuronium

-Atracurium

Which of the following drugs undergoes “Hoffmann” elimination.– Succinyl choline– Pancuronium– Vecuronium

-Atracurium

Pseudocholinesterase can metabolize the following drugs, EXCEPT

 • Succinylcholine• Procaine• Acetylcholine• Bethanechol

Timolol reduces the intraocular pressure by• Reducing the aqueous humor secretion• Producing miosis• Producing mydriasis• Constricting the ciliary blood vessels

The anticholinesterase agent not useful in Alzheimer’s disease

• Rivastigmine• Donepezil• Pyridostigmine • Galantamine

All of the following drugs are clinically used in myasthenia gravis EXCEPT

• Neostigmine• Prednisolone • Pyridostigmine• Pilocarpine