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 Water follows down its osmotic gradient

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

Explain the most common side effect of ACE inhibitors?

Answer 10

COUGH ACE also breaks down bradykinin If bradykinin levels build up then this can cause a cough

Question 11

State some other side effects of ACE inhibitors and ARBs. Briefly explain them

Answer 11

Hypotension - over supression of A2, less vasoconstriction and less aldosterone mediated fluid retention Hyperkalaemia - less activity of Na+/K+ ATPase because less aldosterone, K+builds up in circulation Renal failure in patients with renal artery stenosis - A2 usually constricts the efferent arteriole to compensate for the stenosed renal artery, no efferent constriction = no gomerular pressure = no GFR

Question 12

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

Answer 12

Depolarisation causes the opening of voltage-gated calcium channels (VGCC)

This leads to calcium influx

This causes Ca release from the SR

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 – amlodipine

Question 14

Give an example of non-rate limiting and a rate limiting CCB.

Answer 14

Non-rate limiting: Amlodipine Rate limiting: Verapamil

Question 15

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

Answer 15

Dihydropyridines bind to the extracellularly component of the L-type calcium channel 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 and dont cause any negative ionotropy

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 an 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

Stimulation of alpha-1 receptors causes peripheral vasoconstriction

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 so exxagerated relfex tacchycardia

Question 26

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

Answer 26

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

Question 27

What is step 2 in the NICE guidelines for treatment of hypertension?

Answer 27

ACEi & CCB or ACEi & thiazide diuretic

Question 28

What is step 3 in the NICE guidelines for treatment of hypertension?

Answer 28

ACEi & CCB & Thiazide diuretic

Question 29

What is step 4 in the NICE guidelines for treatment of hypertension?

Answer 29

Further diuretic therapy (low-dose spironolactone)

or

Alpha or beta-blocker

Question 30

What is spironolactone?

Answer 30

It is an aldosterone receptor antagonist

Question 31

What is chronic heart failure?

Answer 31

Impaired cardiac function due to ischaemic heart disease, hypertension or cardiomyopathy that results in fluid retention, oedema and fatigue Importantly - cardiac output doesn’t meet body’s demand

Question 32

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

Answer 32

ACEi ARB Beta-blockers Spironolactone

Question 33

Why are over 55s and afro-Caribbeans given different guidelines for hypertension?

Answer 33

ARBs, ACEi, CCBs, Diuretics have similar efficacy ARBs and ACEi are more well tolerated than CCBs and diuretics However, afro-caribbeans have lower renin:A2/aldosterone ratio suggesting their hypertenion is less linked to renin Older you get the less dependent on renin your hypertension becomes as it is more related to atherosclerosis