SNS Antagonists

Question 1

What does α₁ Adrenoceptor do?

Answer 1

Vasoconstriction, Relaxation of GIT

Question 2

What does α₂ Adrenoceptor do?

Answer 2

Inhibition of transmitter release, contraction of vascular smooth muscle, CNS actions

Question 3

What does β₁ adrenoceptor do?

Answer 3

Increased cardiac rate and force, relaxation of GIT, renin release from kidney

Question 4

What does β₂ ​adrenoceptor do?

Answer 4

Bronchodilation, vasodilation, relaxation of visceral smooth muscle, hepatic glycogenolysis

Question 5

What does β₃ ​adrenoceptor do?

Answer 5

Lipolysis

Question 6

How does α₂ receptor-mediated negative feedback work?

Answer 6

NA released from synapse can bind to α₂ receptor on the presynaptic bulb. This reduces synthesis and release of NA from the synapse

Question 7

Name a non-selective adrenoceptor antagonist:

Answer 7

Carvedilol

Question 8

Name an α adrenoceptor selective antagonist:

Answer 8

Phentolamine (α₁₊₂)

Question 9

What does Prazosin selectively antagonise?

Answer 9

α₁

Question 10

Name a β adrenoceptor selective antagonist:

Answer 10

Propanolol (β₁₊₂)

Question 11

What receptor does Atenolol antagonise?

Answer 11

β₁

Question 12

What are the main clinical uses of Adrenoceptor antagonists?

Answer 12

Hypertension

Cardiac Arrhythmias

Angina

Glaucoma

Question 13

What is the definition of Hypertension, and what are the factors that contribute to it?

Answer 13

Sustained diastolic blood pressure greater than 90mmHg

(NICE: <140/90mmHg)

Blood Volume

Cardiac Output

Total Peripheral Resistance

Question 14

What are the sympathetic controls of Blood pressure?

Answer 14

Controls heart via β1 receptors

Main controller: Renin release from kidneys via β1

Question 15

What tissues can anti-hypertensives target?

Answer 15

The heart - cardiac output

Sympathetic nerves that release the vasoconstrictor noradrenaline

The kidney - blood volume/vasoconstriction

Arterioles - peripheral resistance

The brain - blood pressure set point

Question 16

Which organs do beta-blockers target?

Answer 16

The heart and kidneys (β1)

Sympathetic nerves and CNS (β1 + 2)

Question 17

How do beta-blockers work on the heart to lower BP?

Answer 17

Reduce HR and CO via β1 but this effect disappears with chronic treatment as the heart resets itself

Question 18

How do beta-blockers work on the kidney to decrease HR?

Answer 18

β1 antagonism reduces renin production which results in decreased TPR

This leads to reduced production of Angiotensin II a potent vasoconstrictor

Question 19

How do beta-blockers act on presynaptic β-adrenoceptors?

Answer 19

Blockade of the facilitatory effects (positive feedback) of presynaptic β-adrenoceptors on noradrenaline release may also contribute to the antihypertensive effect.

Question 20

What are cardioselective beta-blockers?

Name one

Answer 20

More selective for β₁ receptors

Atenolol

Question 21

What are mixed β-α blockers?

(I would rather die lol)

Answer 21

Carvedilol - a1 blockade gives additional vasodilator properties

Question 22

What is Nebivolol?

Answer 22

A β1 blocker that also potentiates NO

Question 23

What is Sotalol?

Answer 23

A β-blocker that also inhibits K⁺ channels

Question 24

What is the main side-effect of beta-blockers?

What group of patients must you therefore be careful when prescribing to?

Answer 24

Bronchoconstriction - Asthma/COPD can be dramatic and life-threatening

Question 25

What are the two other main serious side-effects of Beta-blockers?

Answer 25

Cardiac Failure - need some sympathetic drive to the heart Hypoglycemia - The use of b-antagonists mask the symptoms of hypoglycemia (sweating, palpitations, tremor). Use of non-selective b-antagonists are more dangerous in such patients since they will also block the b2- receptors driven breakdown of glycogen . b1- selective agents may have advantages since glucose release from the liver is controlled by b2- receptors.

Question 26

What are three less serious side-effects of beta-blockers?

Answer 26

Fatigue - less cardiac output and less muscle perfusion. Cold Extremities - Loss of β-receptor-mediated vasodilatation in cutaneous vessels. Bad Dreams

Question 27

What us the main advantage of Atenolol over propranolol?

Answer 27

Atenolol β1 selective Propanolol β non-selective Decreased side effects with Atenolol as they tend to be due to β₂ receptors, however they are not fully selective so some side-effects may remain

Question 28

What is the advantage of Carvedilol over Atenolol?

Answer 28

In reducing BP, both reduce Renin secretion and contractility, but Carvedilol also reduces vasoconstriction and therefore TPR due to alpha1 blockade

Question 29

How do α₁ receptors work?

Answer 29

Gq linked receptors

Question 30

How do α₂ receptors work?

Answer 30

Gi linked receptors

Question 31

What is prazosin and how does it work?

Answer 31

Highly selective α1 antagonist Hypotensive via inhibition of vasoconstriction Also causes decrease in LDLs and increase in HDLs

Question 32

What is Phentolamine and how does it work?

Answer 32

Non-selective α antagonist Hypotensive via inhibition of alpha mediated vasoconstriction Also blocks presynaptic α2 inhibitory effects so increased NA which enhances reflex tachycardia

Question 33

What are the side-effects of α-blockers?

Answer 33

Postural Hypotension - when you stand up SNS kicks in to give boost to BP, which is blocked Reflex Tachycardia Increased GIT motility

Question 34

Why does phentolamine have reduced effectiveness due to α₂ receptors?

Answer 34

Blocks α2 inhibitory effect, so there is an increase in NA release which enhances the reflex tachycardia

Question 35

What does methyldopa create?

Answer 35

A false-transmitter - alpha-methylnoradrenaline

Question 36

How do false-transmitters work to reduce hypertension?

Answer 36

Methylnoradrenaline displaces NA from synaptic vesicles Far less active on α1 receptors than NA therefore less effective at causing vasoconstriction It is also **more** active on α2 receptors reducing NA release

Question 37

What are the side-effects of Methyldopa?

Answer 37

Dry mouth, sedation, Orthostatic hypotension, Male sexual dysfunction

Question 38

Why are Beta-blockers given to patients with arrhythmias?

Answer 38

An increase in sympathetic drive to the heart via b1 can precipitate or aggravate arrhythmias. Particularly after myocardial infarction there is an increase in sympathetic tone. AV conductance also depends critically on sympathetic activity, and the refractory period of the AV node is increased by b-adrenoceptor antagonists, interfering with AV conduction in atrial tachycardia's, and to slow ventricular rate. Reduce heart rate so reduces the severity of arrhythmias

Question 39

How do beta-blockers reduce angina?

Answer 39

Angina is pain that occurs when O2 supply to myocardium is insufficient At low doses, b1-selective agents, metoprolol, reduce heart rate and myocardial contractile activity without affecting bronchial smooth muscle. O2 demand is reduced whilst the same degree of effort is maintained

Question 40

How do beta-blockers treat glaucoma?

Answer 40

They reduce the production of Aqueous humour by blocking the receptors on the ciliary body