SNS antagonists

Question 1

How does methyldopa work?

Answer 1

• Methyldopa takes place of DOPA in NA synthesis
• Converted to alpha-methyl NA (false transmitter)
• Less active at a1/b R - less effective at vasoconstriction
• More active on a2 Rs - autoinhibitory fb mech –> reduces NA release below normal levels
• Some CNS effects - stimulates vasopressor centre in BS to inhibit symp outflow –> improved blood flow
• Not metabolised by MAO
• More likely to accumulate and displace NA in vesicle

Question 2

What are the clinical uses of methyldopa?

Answer 2

• Anti-hypertensive in pregnant women (no adverse effects on foetus despite crossing blood-placenta barrier)
• Also in kidney disease and cerebrovascular disease

Question 3

What are the side effects of methyldopa?

Answer 3

• Dry mouth
• Sedation
• Orthostatic hypotension
• Male sexual dysfunction

Question 4

What are the main clinical uses of adrenoceptor antagonists and false transmitters?

Answer 4

• Hypertension
• Cardiac arrhythmias
• Angina
• Glaucoma

Question 5

What are the unwanted effects of alpha adrenoceptor antagonists?

Answer 5

Postural hypotension

Question 6

What are the unwanted effects of beta antagonists?

Answer 6

Negative effects from b2 blockade:

1. Bronchoconstriction - bad for asthma/COPD
2. Cardiac failure - need some symp drive to heart to maintain adequate CO
3. Hypoglycaemia - masks symptoms (sweating, palpitations, tremor)
4. Block b2-mediated glycogenolysis - bad for diabetics
5. Fatigue - reduced CO and muscle perfusion; impairs exercise
6. Cold extremities - loss of bR-mediated vasodilation in cutaneous vessels
7. Bad dreams

Question 7

What is the mechanism of action of propranolol (non-selective beta antagonist)?

Answer 7

Positive effects from b1 blockade:

• Decrease HR, FoC, CO
• Heart doesn’t have to work as hard
• Reduced BP
• Decrease renin
• Decrease AngII
• Less vasoconstriction, less aldosterone
• Decreased TPR
• Block positive facilitatory effects of presynaptic b1Rs on NA release

Question 8

What is the main clinical use of propranolol (non-selective beta antagonist)?

Answer 8

Anti-hypertensive (during exercise)

Question 9

What are the main clinical uses of atenolol (cardioselective b1 antagonist)?

Answer 9

Beta blocker for CV diseases: hypertension, angina, acute MI, long QT syndrome, tachycardia

Question 10

What are main clinical uses of carvediol (mixed B and a antagonist)?

Answer 10

• Mild to severe congestive HF
• Left ventricular dysfunction following heart attack in otherwise stable patients
• Anti-hypertensive

Question 11

What are the 4 different types of SNS antagonists?

Answer 11

1. Non-selective - propranolol
2. b1-selective - atenolol
3. Mixed a-b blockers - carvedilol
4. Other - nebivolol - B1, also potentiates NO, sotalol - B, also inhibits K channels

Question 12

What is the clinical use of phentolamine (non-selective alpha antagonist)?

Answer 12

Phaechromocytoma-induced hypertension

Question 13

What is the clinical use of prazosin (selective a1 antagonist)?

Answer 13

Anti-hypertensive

Question 14

What are the effects of a1 stimulation?

Answer 14

Vasoconstriction

GIT relaxation

Question 15

What are the effects of a2 stimulation?

Answer 15

Inhibition of transmitter release (presynaptic - NA)
Contraction of VSM
CNS actions

Question 16

What are the effects of b1 stimulation?

Answer 16

Inotropic effect
Chronotropic effect
GIT relaxation
Renin release

Question 17

What are the effects of b2 stimulation?

Answer 17

Bronchodilation
Vasodilation
relaxation of visceral SM
Hepatic glycogenolysis

Question 18

What are the effects of b3 stimulation?

Answer 18

Lipolysis

Question 19

How does the sympathetic NS control BP?

Answer 19

SNS controls heart via b1Rs
Major controller = symp drive to kidneys controlling rening release (b1)
Renin release
ATII production
Powerful vasoconstrictor
Aldosterone production
Increases BP

Question 20

What tissues do anti-hypertensives target?

Answer 20

Kidneys - regulate blood volume and vasoconstriction (renin)
Heart
Arterioles - determine TPR (a1-mediated vasoconstriction)
Symp nerves that release NA (vasoconstrictor)
CNS - determines BP set point

Question 21

Do beta-blockers affect arterioles?

Answer 21

No

Do not antagonise a1 receptors

Question 22

What are the side effects of propranolol (non-selective beta antagonist)?

Answer 22

All typical adverse effects due to b2 antagonism

Question 23

What is the mechanism of action of atenolol (cardioselective b1 antagonist)?

Answer 23

• Mainly antagonises effect of NA in heart - reduces HR, BP, CO
• Also affects any tissue with b1R, e.g. kidneys

Question 24

What are the side effects of atenolol (cardioselective b1 antagonist)?

Answer 24

• Typical adverse effects due to b2 antagonism
• Less effect on airways than non-selective drugs, but still not safe for asthmatics
• Higher T2DM risk

Question 25

What is the mechanism of action of phentolamine (non-selective alpha antagonist)?

Answer 25

- Vasodilation and reduced BP due to a1 blockade - a2 blockade removes inhibitory effect of a2Rs on NA release --> increased NA release --> more NA in synapse to compete with drug

Question 26

What are the side effects of phentolamine (non-selective alpha antagonist)?

Answer 26

- Increased GIT motility - diarrhoea | - Reflex tachycardia

Question 27

What is the mechanism of action of prazosin (selective a1 antagonist)?

Answer 27

- Inhibits vasoconstrictor activity of NA --> vasodilation and reduced BP - Decreases LDL, increases HDL cholesterol - Decreases CO due to fall in venous pressure as a result of dilation of capacitance vessels

Question 28

What are the side effects of prazosin (selective a1 antagonist)?

Answer 28

- Reflex tachycardia | - Postural hypotension

Question 29

What is an arrhythmia?

Answer 29

Irregular heart beat

Question 30

What is the main cause of death from an arrhythmia?

Answer 30

Myocardial ischaemia

Question 31

Why are beta blockers a good way of controlling arrhythmias?

Answer 31

- Beta blockers modulate sympathetic drive - Sympathetic drive controls pacemaker current and atrioventricular conductance - Increase in sympathetic drive to heart via B1 can precipitate or aggravate arrhythmias - Beta blockers INCREASE AVN REFRACTORY PERIOD - Interferes w/AV conduction in atrial tachycardias and slows down ventricular rate - Re-entry type electrical activity won't stimulate another heart beat bc still in refractory period

Question 32

Which class of SNS antagonist may be used as an anti-arrhythmic?

Answer 32

- Propranolol - non-selective beta antagonist - Positive effects mainly from B1 antagonism - Reduces mortality of MI patients - Particularly successful in arrhythmias that occur during exercise or mental stress

Question 33

What is angina?

Answer 33

Pain that occurs when the oxygen supply to the myocardium is insufficient for its needs - Pain in chest, arm, neck - Tends to be brought on by exertion or excitement

Question 34

What are the types of angina and what causes them?

Answer 34

1. Stable - pain on exertion due to a fixed narrowing of the coronary vessels (e.g. atheroma) leading to an increased demand on the heart 2. Unstable - pain w/less and less exertion; culminates w/pain at rest; atheromatous plaque starting to rupture; platelet-fibrin thrombus forms but w/o complete occlusion of vessel; high risk of infarction 3. Variable - occurs at rest; caused by coronary artery spasm; associated w/atheromatous disease

Question 35

What class of SNS antagonist may be used to treat angina?

Answer 35

Beta 1 antagonist

Question 36

Why are b1 antagonists used to treat angina?

Answer 36

- At low doses, they reduce myocardial oxygen demand by decreasing HR, SBP and cardiac contractile activity without affecting bronchial smooth muscle - Match oxygen demand to amount of work required - Beta blocker + exercise --> can do same level of work at much lower HR --> heart has to work less hard --> decreased myocardial oxygen demand

Question 37

What are the adverse effects of using a beta blocker in angina?

Answer 37

- Fatigue - Insomnia - Dizziness - Sexual dysfunction - Bronchospasm - Bradycardia - Heart block - Hypotension - Decreased myocardial contractility

Question 38

When should beta blockers not be used in angina?

Answer 38

- Bradycardia (<55) bc you risk further compromising symp drive to heart - Bronchospasm - Hypotension (SBP<90) - AV block or severe congestive HF - risk MI

Question 39

How do selective and non-selective beta antagonists help treat glaucoma?

Answer 39

- Aqueous humour is produced by blood vessels in ciliary body via actions of carbonic anhydrase - Reduce rate of AH formation by blocking B1 receptors on ciliary body --> reduced CA activity producing bicarbonate

Question 40

Why do a1-selective antagonists cause less tachycardia than non-selective a antagonists?

Answer 40

- a1-selective have no a2 effect - tf don't remove inhibitory (-ve fb) effect of a2Rs on NA release on presynaptic membrane - Decrease NA release - Less tachycardia