muscarinic pharmacology Flashcards
what concentrations of Ach are required for muscarinic action
low concentrations of Ach are required for muscarinic activation, nicotinic actions requier high Ach concentrations
what is dale’s experiment?
dale measured blood pressure in response to different concentrations of Ach and presence of hexamothonium and atropine
small dose of Ach causes muscarinic actions; vasodilation
this is repeated in presence of atropine, no change in blood pressure seen
larger dose of Ach in presence of atropine stimulates ganglia, causes increase in blood pressure.
a secondary peak is also seen due to delayed action on adrenal medulla; causing vasoconstriction and tachycardia
hexamethonium is then added, reducing blood pressure to normal by inhibiting Ach nicotinic action
how are muscarinic receptors activated endogenously and what is their effect?
muscarinic receptors are innervated except in most blood vessels excluding genitals
stimulation of muscarinic receptors causes smooth muscle in eye, bronchi, GIT, and bladder to contract
in blood vessels including genitals muscarinic receptors cause smooth muscle relaxation/ vasodilation
in glands they cause secretion
in heart they slow rate via the vagus nerve which innervates SAN and AVN and conduction, but no effect on force of contraction
what are agonists of acetylcholine receptors and which ones do they work on, and what is rate of hydrolysis by cholinesterase
Ach: agonist for both N and M, quickly hydrolysed by cholinesterase
methacholine: agonist only for M, slowly hydrolysed by cholinesterase
carbachol: agonist for both N and M, resistant to cholinesterase
bethanechol, pilocarpine and muscarine: all only M agonists, and resistant to cholinesterase
what is the effect of atropine? and how is it used therapeutically
atropine is muscarinic antagonist
may increase heart rate, cause pupil dilation and paralysis of eye accommodation
is an antiemetic (used to treat motion sickness), used to treat parkinsons to reduce tremor,
what happens when muscarinic receptors in eye are activated
pupil constriction, ciliary muscles contract causes lens to relax into fat shape which accomodates for near vision
what are muscarinic agonists used for therapeutically?
treatment of glaucoma, since ciliary eye spasm helps drain aqueous humour
treatment of dry mouth
to relieve paralytic ileus after surgery
to relieve urinary retention
what are muscarinic antagonists used for therapeutically and what are main 3 drugs used
anaesthesia
to reduce the effects of cholinesterase inhibitors, such as in anticholinesterase poisoning
used to induce mydriasis and ciliary muscle paralysis
relief of smooth muscle spasm such as in COPD
treatment of parkinsons, motion sickness, urinary incontinence
main 3 drugs used: atropine, hyoscine and homatropine, all competitive antagonists
what other drugs can block muscarinic receptors
antipsychotics, antidepressants and antihistamines may sometime block muscarinic receptors
how do parasympthamimetic drugs act on muscarinic receptors
stimulate them, either via direct stimulation of by inhibiting ChE
what main agonist drugs of MAchRs are used clinically and why?
methacholine and carbachol since they have a longer duration of action than Ach since no cholinesterase hydrolysis
how are muscarinic agonist drugs administered
methacholine and carbachol are fully ionised, so not given orally
pilocarpine only partially ionised at physiological pH so is absorbed topically
what are physiological effects of muscarinic antagonist drugs in periphery
resembles activation of sympathetic system:
block of secretions
tachycardia: due to block of vagal inhibition of heart, no change in blood pressure since most blood vessels do not have parasympathetic innervation
pupillary dilation (mydriasis), cycloplegia (cilliary muscle paralysis)
inhibition of motility and secretions of GIT
other smooth muscle relaxed
what are physiological effects of muscarinic antagonists on CNS
atropine has no great effect in small doses, but at high doses causes stimulation, restlessness, hallucinations and disorientation
hyoscine is powerful CNS depressant, causing sleep and amnesia, also an anti-emetic
atropine like drugs supress tremor in parkinsons
how are muscarinic receptors characterised
they are blocked by atropine
