Drugs of the Cardiovascular System – The Vasculature

Question 1

Name the first line treatments for hypertension

Answer 1

<55: ACE inhibitors or Angiotensin Receptor Blockers

>55 or afrocarribean: Calcium channel blockers or Thiazide like diuretics

Question 2

What are the second, third and fourth line treatments for hypertension?

Answer 2

2nd: CCB/ Thiazide like diuretic + ACEi/ ARB
3rd: ACEi/ ARB + CCB + Thiazide like diuretic
4th: = resistant hypertension. Consider spironolactone or A- or B-blocker

Question 3

Name 3 things that drive renin production in the kidney

Answer 3

Decreased Na+ reabsorption
Decreased renal perfusion pressure
Increased sympathetic activity

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

Reduce production of AII, thus inhibiting its effects of:
Vasoconstriction
Increased thirst
SNS activation
Increased salt retention in kidney
Increased aldosterone secretion

Question 6

What law links venous return to contractility?

Answer 6

Starling’s Law

Question 7

How can blockade of vasoconstriction and decreased salt and water retention caused by ACEi be used in treating hypertension?

Answer 7

Vasoconstriction increases TPR
Increased TPR increases BP + venous return
Increased venous return increases contractility + CO
Blockade decreases TPR + BP
Decreased salt + water retention decreases volume in blood system, so BP deceases

Question 8

How can blockade of vasoconstriction and decreased salt and water retention caused by ACEi be used in treating heart failure?

Answer 8

Increased vasoconstriction increases afterload + cardiac work.
Increased venous return causes congestion + oedema.
Blockade reduces afterload.
Decreased salt + water retention means less volume is returned to the heart, thus decreases cardiac work

Question 9

Give an example of an angiotensin receptor blocker. How do these drugs work?

Answer 9

Losartan
Antagonists of type 1 AII receptors
Prevent renal + vascular actions of AII

Question 10

What is the most common side effect of ACE inhibitors? Why?

Answer 10

COUGH
Breakdown of bradykinin is inhibited
Bradykinin is pro-cough

Question 11

State 3 other side effects of ACE inhibitors and ARBs.

Answer 11

Hypotension
Hyperkalaemia
Renal failure in patients with renal artery stenosis

Question 12

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

Answer 12

Depolarisation causes opening of VGCC
Allows Ca2+ influx
Ca2+ binds to calmodulin forming a Ca2+-CaM complex
This complex binds to + activates Myosin Light Chain Kinase (MLCK)
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 e.g. Amlodipine (does not cause negative inotropy)

Question 14

How do calcium channel blockers reduce blood pressure?

Answer 14

Blockade of channels inhibits entry of Ca2+ into vascular smooth muscle cells
Allows vasodilation
Decrease in TPR results in decrease in BP

Question 15

What may be an unwanted result of CCB usage?

Answer 15

Powerful vasodilation can lead to reflex tachycardia + increased inotropy, thus increasing myocardial oxygen demand

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

Why might alpha adrenoceptor antagonists be used as anti-hypertensives?

Answer 17

Blockade of A1 receptors blockades vasoconstriction
Lowers TPR
Lowers BP

Question 18

Give an example of an alpha-1 blocker.

Answer 18

Prazosin

Question 19

Give an example of a non-selective alpha blocker.

Answer 19

Phentolamine

Question 20

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

Answer 20

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

Question 21

What is spironolactone?

Answer 21

An aldosterone receptor antagonist

Question 22

What is chronic heart failure?

Answer 22

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

Question 23

Which 4 drugs are normally used on patients with chronic heart failure?

Answer 23

ACEi
ARB
Beta-blockers
Spironolactone

Question 24

How do arterioles contribute to blood pressure?

Answer 24

Arteriole contraction decreases the radius, so there is less space for blood to pass through thus resistance increases

Question 25

What defines hypertension?

Answer 25

Sustained BP >140/90 mmHg

Question 26

How can ACEi and ARBs cause hyperkalaemia?

Answer 26

Inhibition of Na+ reabsorption means K+ exchange is reduced

Thus K+ accumulates in blood instead of being excreted in urine

Question 27

How can ACEi and ARBs cause renal failure in patients with renal artery stenosis?

Answer 27

Blocking ability of AII to constrict the efferent arteriole in the glomerulus means a fall in GFR can’t be recovered from
Exacerbates failure

Question 28

Why is first line treatment of hypertension different in the elderly?

Answer 28

Hypertension is more likely to be associated to atherosclerosis or other issues
Thus, targeting the RAAS system would have little effect
(low plasma renin activity)