Cholinergic Receptors Flashcards Preview

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Flashcards in Cholinergic Receptors Deck (34):

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

Muscarinic actions produced by muscarine and antagonised by atropine


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

Nicotinic actions produced by nicotine and antagonised by tubocurarine


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

Potently, tubocurarine, hexamethonium


By definition all muscarinic receptors are blocked by _______



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

ACh, externally-applied agonists


Parasympathomimetic drugs

Mimic the effects of stimulating parasympathetic nerves


How do parasympathomimetic drugs act

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


Selectivity and speed of hydrolysis by ChE of ACh

N M, Rapid


Selectivity and speed of hydrolysis by ChE of Carbachol

N M, No


Selectivity and speed of hydrolysis by ChE of Methacholine

M, Slow


Selectivity and speed of hydrolysis by ChE of Bethanecol

M, No


Selectivity and speed of hydrolysis by ChE of Pilocarpine

M, No


Why are methacholine and carbachol more useful clinically than ACh?

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


Why are methacholine and carbachol not given orally?

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


Why can pilocarpine be used topically?

Tertiary amine which is only partly ionised at physiological pH


Main effects of muscarinic agonists

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


Main clinical uses of muscarinic agonists:

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 Relief of urinary retention, when this results from failure of normal reflex pathway acting on bladder ( bethnechol; superseded by catherisation)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)


Competitive antagonists block _____ receptors without much _____

muscarinic, selectivity


3 main antagonists at muscarinic receptors

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


How are CNS effects avoided when using muscarinic antagonists?

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


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

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


Where is the site of a muscarinic receptor block?

At the organs innervated by It rather than PNS


Peripheral inhibition of muscarinic receptor effects

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


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

Most blood vessels have no parasympathetic innervation


Why mydriasis a bad thing?

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


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

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


Atropine actions on CNS

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


Hyoscine on CNS

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


Atropine-like drugs on CNS

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


2 therapeutic uses of inhibitors in anaesthetia

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?


2 therapeutic uses of inhibitors in opthamology

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


What precaution needs to be taken when using inhibitors in opthamology

Pupilary dilation can increase IO pressure -> dangerous in glaucoma


Why are atropine/ hyoscine not used for opthalomogical exams?

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


What other therapeutic uses are there for inhibitors?

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)