Drugs of the Cardiovascular System – The Vasculature

Question 1

Name three drug classes that interfere with the renin-angiotensin system.

Answer 1

Renin inhibitors
ACE inhibitors
Angiotensin receptor blockers

Question 2

Describe the action of aldosterone in collecting duct tubule cells.

Answer 2

Aldosterone passes through the plasma membrane and binds to mineralocorticoid receptors intracellularly and increases the synthesis of Na+ channels and Na+/K+ pumps
This causes an increase in sodium reabsorption

Question 3

What are the uses of ACE inhibitors?

Answer 3

Hypertension  
Heart Failure  
Diabetic Nephropathy 
Post-MI
Progressive Renal Insufficiency  
Patients at high risk of cerebrovascular disease

Question 4

Give an example of an ACE inhibitor.

Answer 4

Enalapril

Question 5

What are the anti-hypertensive effects of ACE inhibitors?

Answer 5

They reduce the production of angiotensin II, which is a potent vasoconstrictor
It also reduces the production of aldosterone, thus reducing salt and water retention
This means that there is a decrease in blood volume, hence a decrease in venous return

Question 6

What law links venous return to contractility?

Answer 6

Starling’s Law

Question 7

What is diabetic nephropathy caused by?

Answer 7

It is due to significant damage to the kidney glomerulus because of toxic products
NOTE: hyperglycaemia increases the risk of exposure to oxygen free radicals

Question 8

Why are ACE inhibitors used in diabetic nephropathy?

Answer 8

ACE inhibitors reduce the angiotensin II-mediated vasoconstriction of the efferent arteriole
This reduces the blood pressure at the glomerulus and hence reduces the accumulation of toxic products at the glomerulus

Question 9

Give an example of an angiotensin receptor blocker.

Answer 9

Losartan

Question 10

What is the most common side effect of ACE inhibitors?

Answer 10

COUGH

Question 11

State some other side effects of ACE inhibitors and ARBs.

Answer 11

Hypotension  
Urticaria/Angioedema (ACEi – very rare) 
Hyperkalaemia  
Fetal injury 
Renal failure in patients with renal artery stenosis (due to both)

Question 12

Describe the excitation-contraction coupling of vascular smooth muscle cells.

Answer 12

Deplarisation causes the opening of voltage-gated calcium channels (VGCC)
This leads to calcium influx
The calcium then binds to calmodulin forming a Ca2+-CaM complex
This complex activates Myosin Light Chain Kinase (MLCK), and the MLCK-mediated phosphorylation leads to smooth muscle contraction

Question 13

What type of calcium channel blocker is more selective for blood vessels? Give an example.

Answer 13

Dihydropyridines – nicardipine

Question 14

Give two examples of non-rate slowing CCBs.

Answer 14

Nicardipine
Nitrendipine
Amlodipine
Nisoldipine

Question 15

Which part of the calcium channel do the different CCBs bind to?

Answer 15

Dihydropyridines bind to the extracellularly component of the calcium channel
Diltiazem and verapamil binds to the intracellular component so for a CCB to have an effect on the heart it needs to be able to penetrate the membrane and act on the receptor inside the cell

Question 16

Why are non-rate slowing CCBs preferred to rate-slowing CCBs in the treatment of hypertension and heart failure?

Answer 16

They have a more powerful effect on vascular smooth muscle

Question 17

What type of receptor is a beta adrenoceptor?

Answer 17

G-protein coupled receptor (Gs protein linked)

Question 18

What are the effects of noradrenaline that cause an increase in blood pressure?

Answer 18

Increase in heart rate and cardiac contractility (leads to increase in CO) via beta-1 receptors in the heart
Stimulation of beta-1 receptors in the kidneys promotes renin release –> increase in angiotensin II

Question 19

What is hypertension in younger patients normally caused by?

Answer 19

Increased sympathetic drive

Question 20

State some uses of beta-blockers.

Answer 20

Angina 
Post-MI
Cardiac dysrhythmias  
Chronic heart failure
Hypertension  
Also thyrotoxicosis, glaucoma, anxiety states, migraine prophylaxis, benign essential tremor

Question 21

Give an example of a cardio-selective beta-blocker.

Answer 21

Atenolol

Question 22

What are mixed beta-alpha blockers? Give an example.

Answer 22

They are beta-1, beta-2 and alpha-1 blockers
Carvedilol
You get extra vasodilation due to alpha-1 blockade

Question 23

Give an example of an alpha-1 blocker.

Answer 23

Prazosin

Question 24

Give an example of a non-selective alpha blocker.

Answer 24

Phentolamine

Question 25

Why is it important for alpha-1 blockers to be selective?

Answer 25

Alpha-2 receptors are the negative feedback receptors of the SNS
Blocking them will result in enhancement of sympathetic activity

Question 26

Give an example of a drug that is used to treat migraine and explain how it works.

Answer 26

Sumatriptan
It is a 5-HT (serotonin) receptor agonist, which causes vasoconstriction of some of the large arteries in the brain and inhibits trigeminal nerve transmission
NOTE: painful stimuli is transferred by the trigeminal nerve and profound vasodilation is also associated with migraine

Question 27

When is sumatriptan contraindicated?

Answer 27

Coronary disease

Question 28

What are the side effects of sumatriptan?

Answer 28

Dizziness, drowsiness, asthenia/fatigue

Question 29

What is step 1 in the NICE guidelines for treatment of hypertension?

Answer 29

< 55 years = ACEi + ARB

>55 years or Afro-Caribbean of any age = CCBs + thiazide-type diuretics

Question 30

What is step 2?

Answer 30

ACEi or ARB

AND CCB or thiazide diuretic

Question 31

What is step 3?

Answer 31

ACEi/ARB
CCB
Thiazide diuretic

Question 32

What is step 4?

Answer 32

Further diuretic therapy (low-dose spironolactone)

Alpha or beta-blocker

Question 33

What is spironolactone?

Answer 33

It is an aldosterone receptor antagonist

Question 34

What is chronic heart failure?

Answer 34

Impaired cardiac function due to ischaemic heart disease, hypertension or cardiomyopathy that results in fluid retention, oedema and fatigue