SNS antagonists Flashcards
What are the 2 main roles of alpha 1 adrenoceptors?
Vasoconstriction + GIT relaxation
What subtype of G protein are alpha 1 adrenoceptors linked to?
Gq
What are the 2 main roles of alpha 2 adrenoceptors?
Neg. feedback at presynaptic terminal
CNS actions
What subtype of G protein are alpha 2 adrenoceptors linked to?
Gi
What are the 2 main roles of beta 1 adrenoceptors?
- Increase HR and contractility
2. Increase renin release
What are the 2 main roles of beta 2 adrenoceptors?
Bronchodilation
Vasodilation
What is the main role of beta 3 receptors?
Lipolysis
Give an example of a selective alpha 1 antagonist
Prazosin
What is the main clinical use of alpha antagonists?
TPR decrease
Give an example of a non-selective alpha antagonist
Phentolamine
Where do non-selective antagonists act other than alpha receptors?
Baroreceptors
Difficult – why do alpha 2 receptors and baroreceptors reduce the effectiveness of phentolamine?
A2 blockade- loses negative feedback and so more NA released into synapse. NA competes with phentolamine for a1 blockade and eventually outcompetes phentolamine as NA conc goes up
Baroreceptor reflex triggered which causes heart to beat quicker and stronger whilst the phentolamine is dilating the vessels and this is not good for the heart. (Although TPR will have greater influence on overall BP, it is still not great for the heart )
What is the main side effect of phentolamine and why?
alpha receptors NORMALLY:
Decrease motility + tone, Sphincter contraction. ie decreases GIT activity
Blocking this = increased motility + tone and sphincter relaxation
= DIARRHOEA
Give 2 examples of selective beta 1 antagonists
Atenolol, nebivolol
Remember from coursework= atenolol is better than pindolol due to less reflex tachycardia because of its B1 selectivity
Clinical use of beta blockers?
Anti-hyertensives
Anti-arrhythmic
Angina
Glaucoma
Recall 6 possible side effects of beta receptor antagonism
- Bronchoconstriction (caution: asthma)
- Reduced Hepatic glucose release + masking symptoms of hypoglycaemia (caution: diabetics)
- Reduced SNS action on heart (caution: heart failure)
- Fatigue
- Cold extremities
- Bad dreams due to CNS effects
Give 2 examples of non-selective beta antagonists
Propanolol
Carvedilol
Recall the selectivity of carvedilol
Beta 1, beta 2, alpha 1
Recall an advantage and a disadvantage of carvedilol use
Advantage: antagonises beta and alpha 1 receptors so pronounced effect on BP
Disadvantage: significant side effect profile
Give an example of a false transmitter
methyldopa
MOA of false transmitter
Methyldopa is basically an altered version of DOPA (physiological NA precursor). The alpha-methylnoradrenaline from methyldopa is similar to NA but a less powerful agonist for a1, b1 and b2 BUT a better agonist for a2. alpha methyl-NA gets released into synaptic cleft. After its reuptake via uptake 1, it is resistant to MAO-A metabolism hence builds up in presynaptic terminal and eventually reaches high enough concentration to displace NA in the vesicles and be released again back into the synapse
Main effect of methyldopa
postural hypotension (theyre too good at what they do)
How does the sympathetic nervous system worsen arrhythmias and therefore which class of drugs would you use ?
B1 receptor involved in
- HR and contractility
- facilitates AV conductance
Use beta blockers eg propanolol
3 types of angina
stable - atherosclerosis
unstable - bad atherosclerosis leading to significant narrowing/rupture causing a thrombus
variable - narrowing is due to coronary artery vasospasm rather than atherosclerosis but can be associated with it
Summarise how b blockers help with angina
reduce the demand on the heart (think of demand supply)
- reduce HR
- reduce contractility
outline how b blockers can be used for glaucoma
B1 receptor drives Aqueous humour Production. Beta blockers Can block this and hence Reduce b1 stimulation and less
Aqueous humour production
