[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

Synthesis of ACH

Arrival of impulse
Synthesis, Storage & release

of Ach by exocytosis
Combination of Ach With receptors Postjunctional activity: Excitatory[EPSP] or Inhibitory[IPSP] Termination of

ATP + Acetate + CoEn-A

= Acetyl CoEn-A + [acetyl transferase] Choline

Acetylcholine + CoEn-A

Ach action hydrolysis by true cholinesterase

Q. Classify anti-cholinesterases with examples. Discuss the pharmacotherapy of organophosphorous poisoning. 3+2
Ans. 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 analogues Eg. Latanoprost 2. Adrenergic blockers Eg. Timolol 3. Adrenergic agonists Eg. Apraclonidine 4. Carbonic anhydrase inhibitors Eg. Acetazolamide 5. Miotics Eg. Pilocarpine 6. Mannitol MOA of latanoprost oMOA- Increases permeability of tissues in ciliary muscles Increases uveo-scleral outflow May also increase trabecular out

flow

Q. Enumerate mydriatics. Discuss the uses of various mydriatics 2+3

Ans. Mydriatic 1. Adrenergic agonists -Eg. Phenylephrine 2. Antimuscarinics- Atropine, Homatropine, tropicamide, Cyclopentolate, 3. Anticholinesterases- Physostigmine 4. Ganglionic blockers- Eg. Hexamethonium Uses 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/cornea To give rest to internal ocular muscles and as anodyne in inflammatory conditions of eye like iridocyclitis[ Atropine]

1. 2. 3. 4.

Q. Name two cholinesterases. Mention differences between them. 1 + 2

Ans. 1. Two cholinesterases Acetyl cholinesterase[true] 2. Butyrylcholinesterase [pseudo] Differences
Parameters Distribution True Cholinergic sites RBC, gray matter Very fast Sensitive to Physostigmine Termination of Ach action No effect Pseudo Plasma, Liver, intestine, white matter Slow Sensitive to OPs Hydrolysis of ingested esters Hydrolysis

Effect on ACh Inhibition Function Succinylcholine

Write briefly on Edrophonium test.

[Tensilon]Edrophonium test To aid diagnosis i.v.2 mg of edrophonium chloride45 seconds 8 mg if the first dose is without effect Brief improvement in strength MG diagnosis To 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
Receptor

Location
Gastric glands, Autonomic ganglia & CNS SA node, AV node, Atrium, Ventricle, Auto receptors

M1 M2 M3

Visceral smooth muscle, Iris, Ciliary muscle, Exocrine glands, Vascular endothelium.

M4
M5

CNS

NM NN

NM junction
Autonomic ganglia, Adrenal medulla

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

2 Ans.

Unlike physostigmine 1. They have direct action on Nicotinic receptors at NM junction -Hence augmentation of action 2. 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 blocker. It blocks the 2 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

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. 2. 3. 4. 5. 6. Pilocarpine Timolol Latanaprost Acetazolamide Apraclonidine Mannitol MOA of 2 agonists 2 agonists primarily reduce secretion of aqueous humor by acting on the 2 receptors on the ciliary body. Subsidiary action is their 1action, constriction of ciliary blood vessels, reduction in the synthesis of aqueous humor

Q. Uses and adverse effects of neuromuscular blockers 5

Uses

Ans.

Adverse effects

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

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.]

Mention any SIX antimuscarinic agents Mention one use for each 5
Antimuscarinics Uses

1. Atropine 2. Scopolamine 3. Homatropine 4. Glycopyrrolate

5. Benzhexol 6. Ipratropium bromide

1. OP poisoning 2. Travel sickness 3. Mydriatic for testing of errors of refraction 4. Preanestheticantisecretory 5. Parkinsonism 6. As bronchodilator in COPD & Bronchial asthma

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

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 , M 4 , M5 Nicotinic NN, NM

Cholinergic sites M1: Autonomic Ganglia, Gastric glands, CNS M2: SA node, AV node, atrium, ventricle, M3: Visceral smooth muscle Iris, 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 includes A. Dicyclomine B. Clidinium C. Oxybutynin D. Cyclopentolate

MCQ

Miotics include A. Anticholinesterases B. 1 Adrenergic agonists C. Ganglionic blockers D. Antimuscarinics

MCQ

Non-selective betablockers used in the pharmacotherapy of glaucoma includes A. Betaxolol B. Atenolol C. Timolol D. 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 Alzheimers disease Rivastigmine Donepezil Pyridostigmine Galantamine

All of the following drugs are clinically used in myasthenia gravis EXCEPT Neostigmine Prednisolone Pyridostigmine Pilocarpine