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

Give an example of an ACE inhibitor.

Answer 3

Enalapril

Tend to end in il

Question 4

What are the anti-hypertensive effects of ACE inhibitors?

Answer 4

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 5

What law links venous return to contractility?

Answer 5

Starling’s Law

Question 6

What is diabetic nephropathy caused by?

Answer 6

It is due to significant damage to the kidney glomerulus because of toxic products

Question 7

Why are ACE inhibitors used in diabetic nephropathy?

Answer 7

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 8

Give an example of an angiotensin receptor blocker.

Answer 8

Losartan

Question 9

What is the most common side effect of ACE inhibitors?

Answer 9

COUGH due to stopping breakdown of bradykinin which causes cough

Question 10

State some other side effects of ACE inhibitors and ARBs.

Answer 10

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

Question 11

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

Answer 11

Dihydropyridines – nicardipine and amlodipine

Question 12

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

Answer 12

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 13

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

Answer 13

They have a more powerful effect on vascular smooth muscle

Question 14

What type of receptor is a beta adrenoceptor?

Answer 14

G-protein coupled receptor

Question 15

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

Answer 15

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 16

What is hypertension in younger patients normally caused by?

Answer 16

Increased sympathetic drive

Question 17

State some uses of beta-blockers.

Answer 17

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

Question 18

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

Answer 18

Atenolol

Question 19

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

Answer 19

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

Question 20

Give an example of an alpha-1 blocker.

Answer 20

Prazosin

Question 21

Give an example of a non-selective alpha blocker.

Answer 21

Phentolamine

Question 22

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

Answer 22

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

Question 23

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

Answer 23

< 55 years = ACEi + ARB

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

Question 24

What is step 2?

Answer 24

ACEi or ARB
AND CCB or thiazide diuretic
Basically combine them

Question 25

What is step 3?

Answer 25

ACEi/ARB
CCB
Thiazide diuretic

Question 26

What is step 4?

Answer 26

Further diuretic therapy (low-dose spironolactone)
Alpha or beta-blocker
Called resistant hypertension

Question 27

What is spironolactone?

Answer 27

It is an aldosterone receptor antagonist

Question 28

What is chronic heart failure?

Answer 28

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

Question 29

Which drugs are normally used on patients with chronic heart failure?

Answer 29

ACEi
ARB
Beta-blockers
Spironolactone

Question 30

Hypertension definition

Answer 30

BP consistently above 140/90

Question 30

What does BP equal

Answer 30

Total peripheral resistance x CO

Question 30

Drivers behind renin production

Answer 30

SNS
Reduced Na reabsorption
Reduced RPP

Question 30

Angiotensin 2 effects

Answer 30

Thirst feeling
Aldosterone secretion
Salt and water retention
Vasoconstriction

Question 30

How doACEi and ARB cause hyperkalaemia

Answer 30

As less sodium is being reabsorbed in kidney cells less potassium is being excreted from blood due to no concentration gradient being created from no aldosterone increasing Na channels in apical membrane

Question 31

Why are ACEi and ARB bad with renal artery stenosis patients in renal failure

Answer 31

Less angiotensin to constrict efferent arteriole which affects ability to control GFR

Question 32

Why are CCBs preferred to ACEi and ARBs in the elderly and Afro Caribbean’s

Answer 32

They have lower renin

Question 33

How does diabetes lead to increased risk of nephropathy

Answer 33

Hyperglycaemia increases the risk of exposure to oxygen free radicals