Cholinergic Receptors

Question 1

Low doses of ACh cause ___ action produced by X and antagonised by Y

Answer 1

Muscarinic actions produced by muscarine and antagonised by atropine

Question 2

High doses of ACh cause ___ action produced by X and antagonised by Y

Answer 2

Nicotinic actions produced by nicotine and antagonised by tubocurarine

Question 3

While muscle receptors are ____ blocked by _____, ganglion receptors are blocked by ________

Answer 3

Potently, tubocurarine, hexamethonium

Question 4

By definition all muscarinic receptors are blocked by _______

Answer 4

atropine

Question 5

Some receptors have no innervation, such receptors do not normally see ___ but respond to ____

Answer 5

ACh, externally-applied agonists

Question 6

Parasympathomimetic drugs

Answer 6

Mimic the effects of stimulating parasympathetic nerves

Question 7

How do parasympathomimetic drugs act

Answer 7

1) By stimulating muscarinic receptors in the same way as ACh (muscarinic agonists)
2) By inhibiting cholinesterase to intensify + prolong action of ACh at synapse

Question 8

Selectivity and speed of hydrolysis by ChE of ACh

Answer 8

N M, Rapid

Question 9

Selectivity and speed of hydrolysis by ChE of Carbachol

Answer 9

N M, No

Question 10

Selectivity and speed of hydrolysis by ChE of Methacholine

Answer 10

M, Slow

Question 11

Selectivity and speed of hydrolysis by ChE of Bethanecol

Answer 11

M, No

Question 12

Selectivity and speed of hydrolysis by ChE of Pilocarpine

Answer 12

M, No

Question 13

Why are methacholine and carbachol more useful clinically than ACh?

Answer 13

Quaternary amines -> Longer duration of action as less quickly broken down by ChE

Question 14

Why are methacholine and carbachol not given orally?

Answer 14

Quaternary amines are fully ionised so not absorbed when given orally nor readily absorbed from conjunctival sac

Question 15

Why can pilocarpine be used topically?

Answer 15

Tertiary amine which is only partly ionised at physiological pH

Question 16

Main effects of muscarinic agonists

Answer 16

1. Bradycardia + reduced CO -> fall in bp
2. Vasodilation
3. Salivation, lacrimation + sweating
4. Bronchoconstriction + increased bronchial secretion
5. Contraction of bladder
6. Increased G.I. motility
7. Pupillary constriction -> low I.O. pressure
8. Ciliary muscle contraction -> near vision accommodation

Question 17

Main clinical uses of muscarinic agonists:

Answer 17

1. Reduction I.O. pressure in glaucoma (pilocarpine)
2. Dry mouth relief (xerostomia; pilocarpine)
3. Relief of urinary retention, when this results from failure of normal reflex pathway acting on bladder ( bethnechol; superseded by catherisation)
4. Increasing G.I. motility during period of inactivity from abdominal surgery ( bethanechol; rarely)

Question 18

Competitive antagonists block _____ receptors without much _____

Answer 18

muscarinic, selectivity

Question 19

3 main antagonists at muscarinic receptors

Answer 19

1. Atropine (nightshade berries)
2. Hyoscine (scopolamine)
3. Homatropine (synthetic analogue of atropine - briefer action)

Question 20

How are CNS effects avoided when using muscarinic antagonists?

Answer 20

Use quaternary derivatives since all 3 muscarinic antagonists are tertiary bases which are readily absorbed + enter brain easily

Question 21

Why are the elderly susceptible to cognitive impairment by antimuscarinic effects?

Answer 21

Many common classes of drugs have antimuscarinic side effects -> several types of drugs will have accumulated side effects

Question 22

Where is the site of a muscarinic receptor block?

Answer 22

At the organs innervated by It rather than PNS

Question 23

Peripheral inhibition of muscarinic receptor effects

Answer 23

1. Block of secretions: saliva, tears, bronchial secretion, swelling
2. Tachycardia -> block of vagal inhibition of heart
3. Pupillary dilation (mydriasis) -> block of parasymp. influence on sphincter pupillae
4. Inhibition of motility + secretions of GI tract
5. Bronchi + bladder also relaxed

Question 24

Why is there no change in bp when vagal inhibition of heart is blocked?

Answer 24

Most blood vessels have no parasympathetic innervation

Question 25

Why mydriasis a bad thing?

Answer 25

Interfers with drainage via canal of Schlemm + thus raises IO pressure -: cycloplegia hence paralysis of accomodation

Question 26

Which inhibitiory effects require much larger doses and are not even complete?

Answer 26

G.I and smooth muscle since there are other transmitters that maintain G.I. + bladder function even when cholinergic transmission is fully blocked

Question 27

Atropine actions on CNS

Answer 27

No great effect in small doses but in high doses marked stimulation : - restlessness - disorientation - hallucination - > attention + memory deficit at low doses for elderly

Question 28

Hyoscine on CNS

Answer 28

Powerful CNS depressant -: sleep + amnesia | -> anti-emetic action

Question 29

Atropine-like drugs on CNS

Answer 29

supress the tremor of PD probs by blocking cholinergic transmission in basal ganglia

Question 30

2 therapeutic uses of inhibitors in anaesthetia

Answer 30

1. Pre-anaesthetia med to inhibit salivary and bronchial secretion + cause drowsiness (hyoscine) 2. During surgery to prevent vagal inhibition of heart ( occurs with some anaesthetics) + prevent parasympathomimetic actions of anti-cholinesterases -> effect on nmj?

Question 31

2 therapeutic uses of inhibitors in opthamology

Answer 31

1. Dilate pupil fully and paralyse lens for opthalmological examination 2. Prevent contraction of pupil following ophthalmic surgery

Question 32

What precaution needs to be taken when using inhibitors in opthamology

Answer 32

Pupilary dilation can increase IO pressure -> dangerous in glaucoma

Question 33

Why are atropine/ hyoscine not used for opthalomogical exams?

Answer 33

Blur vision for several ays so shorter acting synthetic analogue tropicamide or homatropine used

Question 34

What other therapeutic uses are there for inhibitors?

Answer 34

1. Anticholinesterase poisoning 2. Symptomatic relief of sm mu spasm in asthma -> poorly controlled by first-line agents/ bronchodilation COPD 3. PD: initial or with levodopa 4. Prevent motion sickness (hyoscine) 5. Alleviate overactive bladder (tropium)