drugs used in asthma and COPD- anti muscarinic Flashcards
which nervous system are muscarinic receptors found?
at target organs in the parasympathetic system
what type of receptors are muscarinic receptors? what neurotransmitter activates them?
G-protein coupled receptors activated by acetylcholine
how many types of muscarinic receptors are there?
5
what does the M1 muscarinic receptor do?
- know as neural and mainly found in CNS
- signal via the Gq G-protein signal via IP3/Ca2+, increases the second messenger Ca2+ in the cell and inhibition of K+ channels
what does the M2 muscarinic receptor do?
-mainly in the heart
causes decrease in cAMP and activation of K+ channels works via Gi G-protein
what does the M3 muscarinic receptor do?
- found mainy in glands and smooth muscles
- stimulates the Gq and also increases IP3 therfore Ca2+ increases
what does the M4/5 muscarinic receptor do?
found mostly in the CNS
- M4 stimulates Gi decrease in cAMP and activation of K+ channels
- M5 stimulates the Gq and also increases IP3 therfore Ca2+ increases
what will happen if an drug agonists binds to a muscarinic receptor?
it will activate all the M1-5 recepetors
what are drugs that are agonists muscarinic receptors are termed?
parasympathomimetics
what are drugs that are antagonists muscarinic receptors are termed?
parasympatholtics due to their inhibition
what is xanomeline?
it is a M1 muscarnic sub-type receptor developed for alzeheimers but had bad side effects
what is cevimeline?
is selective for M3 used for sjogren sydndrome, but not license in the UK
what are some effects of muscarinic agonist on the cardiovascular?
- decrease cardiac output
- increase of NO causing vasodilaton
- decrease blood pressure
what are some effects of muscarinic agonist on the smooth muscle?
- causes contraction of smooth muscle
- increase peristaltic activity
- bladder contraction
- constriction of bronchioles
whats the main clinical use of muscarinic agonists to treat?
- treat glaucoma using the agonist pilocarpine
- treat urinary retention using the agonist bethanecol but have a lot of side effects
what is the main muscarinic antagonist?
atropine, non-selective cant distinguish between M1-5 but can between muscarinic and nicotinic receptors
what are some other muscarinic anatagonists?
- tiotropium and ipratropium
- hyoscine
- tropicamide
- pirenzepine
- darifenacin
what are some effects of muscarinic antagonist on the cardiovascular system?
- tachycardia, increase HR
- blood pressure unchanged
what are some effects of muscarinic antagonist on the smooth muscle?
- GIT mobility inhibited
- urinary tract relaxation, prevents bladder emptying
- bronchial relaxation
what are some clinical uses of muscarinic antagonists?
used for asthma and airways disease dilation
motion sickness
what are some side effects of muscarinc antagonists?
dry mouth dry skin constipation tachycardia urinary urgency and retention
what nervous system controls broncial smooth muscle contraction?
autonomic
what sub NS controls bronchodilation?
sympathetic
what sub NS controls bronchoconstriction?
parasympathetic
what nerve is stimulated that mediates the effects?
vagus
how does the pathway for nerve stimulation lead to contraction of smooth muscle in bronchiole?
- vagus nerve is stimulates the post ganglionic neuron
- then acytlcholine is released
- which then acts on muscarinic receptors M1/3 on bronchial smooth muscle
- then contraction occurs
how does an agonist cause the constriction of smooth muscle in the bronchi?
an agonist like methacholine acts on receptors to cause constriction
how does an antagonist prevent the constriction of smooth muscle in the bronchi?
antagonist such as ipratropium bromide would block acytlcholine from binding as it would bind its self so contracton is inhibited and bronchodilation would occur
what does an agonist do to the control of bronchial smooth muscles?
causes constriction
what does an antagonist do to control of bronchial smooth muscle?
causes dilation
what are some of the uses of muscarinic antagonists in COPD and asthma?
- they are non-selective (anti muscarinic)
- tiotropium is long acting
- they are poorely absorbed as they are charged so used as inhalation so less systemic action to cause side effects
what commonly used muscarinic antagonists are used for COPD and asthma
ipratropium and tiotropium
which anti-muscarinic is short acting?
iprattropium bromide
what are some key infor about ipratropium?
- brand name is Atrovent
- used for airway obstruction, broncho spasum and acute life threatening asthma
- maximum effect in 30mins
- duration of 3-6hrs
- 3/4 doses =adequate bronchodilation for the -day
what are some key infor for tiotropium?
-brand name is Spiriva
-once daily
hand inhaler only for COPD and respimat inhaler for asthma and COPD
-
why may patients experience adverse effects?
as they are non selective they’ll block on all muscarinic receptors. if given inhalation form they’ll reduce effects
where are anti-muscarincic used for in guidlines?
barely used for asthma
what are the key things to consider when designing a drug from a natural ligand?
- identify types of interaction and structural features
- structure activity relation
- identify a pharmacophore
why is acytlcholine not got a drug structure?
not selective works at both nicotinic and muscarinic
