SNS antagonists

Question 1

What are the 2 main roles of alpha 1 adrenoceptors?

Answer 1

Vasoconstriction + GIT relaxation

Question 2

What subtype of G protein are alpha 1 adrenoceptors linked to?

Answer 2

Gq

Question 3

What are the 2 main roles of alpha 2 adrenoceptors?

Answer 3

Neg. feedback at presynaptic terminal

CNS actions

Question 4

What subtype of G protein are alpha 2 adrenoceptors linked to?

Answer 4

Gi

Question 5

What are the 2 main roles of beta 1 adrenoceptors?

Answer 5

1. Increase HR and contractility

2. Increase renin release

Question 6

What are the 2 main roles of beta 2 adrenoceptors?

Answer 6

Bronchodilation

Vasodilation

Question 7

What is the main role of beta 3 receptors?

Answer 7

Lipolysis

Question 8

Give an example of a selective alpha 1 antagonist

Answer 8

Prazosin

Question 9

What is the main clinical use of alpha antagonists?

Answer 9

TPR decrease

Question 10

Give an example of a non-selective alpha antagonist

Answer 10

Phentolamine

Question 11

Where do non-selective antagonists act other than alpha receptors?

Answer 11

Baroreceptors

Question 12

Difficult – why do alpha 2 receptors and baroreceptors reduce the effectiveness of phentolamine?

Answer 12

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 )

Question 13

What is the main side effect of phentolamine and why?

Answer 13

alpha receptors NORMALLY:
Decrease motility + tone, Sphincter contraction. ie decreases GIT activity

Blocking this = increased motility + tone and sphincter relaxation

= DIARRHOEA

Question 14

Give 2 examples of selective beta 1 antagonists

Answer 14

Atenolol, nebivolol

Remember from coursework= atenolol is better than pindolol due to less reflex tachycardia because of its B1 selectivity

Question 15

Clinical use of beta blockers?

Answer 15

Anti-hyertensives
Anti-arrhythmic
Angina
Glaucoma

Question 16

Recall 6 possible side effects of beta receptor antagonism

Answer 16

1. Bronchoconstriction (caution: asthma)
2. Reduced Hepatic glucose release + masking symptoms of hypoglycaemia (caution: diabetics)
3. Reduced SNS action on heart (caution: heart failure)
4. Fatigue
5. Cold extremities
6. Bad dreams due to CNS effects

Question 17

Give 2 examples of non-selective beta antagonists

Answer 17

Propanolol

Carvedilol

Question 18

Recall the selectivity of carvedilol

Answer 18

Beta 1, beta 2, alpha 1

Question 19

Recall an advantage and a disadvantage of carvedilol use

Answer 19

Advantage: antagonises beta and alpha 1 receptors so pronounced effect on BP
Disadvantage: significant side effect profile

Question 20

Give an example of a false transmitter

Answer 20

methyldopa

Question 21

MOA of false transmitter

Answer 21

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

Question 22

Main effect of methyldopa

Answer 22

postural hypotension (theyre too good at what they do)

Question 23

How does the sympathetic nervous system worsen arrhythmias and therefore which class of drugs would you use ?

Answer 23

B1 receptor involved in
- HR and contractility
- facilitates AV conductance
Use beta blockers eg propanolol

Question 24

3 types of angina

Answer 24

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

Question 25

Summarise how b blockers help with angina

Answer 25

reduce the demand on the heart (think of demand supply)

1. reduce HR
2. reduce contractility

Question 26

outline how b blockers can be used for glaucoma

Answer 26

B1 receptor drives Aqueous humour Production. Beta blockers Can block this and hence Reduce b1 stimulation and less
Aqueous humour production