Drugs and the Vasculature

Question 1

Hypertension is classified as

Answer 1

raised blood pressure 140/90mmHg.

Question 2

How does Angiotensin II promote salt and water retention,

Answer 2

via the stimulation of aldosterone secretion, which promotes sodium retention by binding to the kidneys mineralocorticoid receptors

Question 3

How does Angiotensin II promote increased BP

Answer 3

causes strong vasoconstriction via the AT1 receptor.

Question 4

What stimulates renin secretion

Answer 4

renal perfusion pressure falling and sodium reabsorption falling

Question 5

What cells stimulate renin secretion

Answer 5

sympathetic nervous system on JGA cells

Question 6

MOA of aldosterone?

Answer 6

Aldosterone causes sodium reabsorption and water retention

Aldosterone passes through the cell membrane and binds to the intracellular mineralocorticoid receptor

It then upregulates the production of sodium channels and the production of Na+/K+ ATPase

The presence of more Na+/K+ ATPase means that you get more sodium reabsorption

Question 7

uses of ACEi

Answer 7

Hypertension
	Heart failure
	Post-MI
	Diabetic nephropathy
	Progressive renal insufficiency
•	Patients at high risk of cerebrovascular disease

Question 8

What is enalapril

Answer 8

An ACEi

Question 9

Example of an ACEi

Answer 9

Enalapril

Question 10

What does ACEi do

Answer 10

Inhibit the somatic form of angiotensin converting enzyme (ACE)
Prevent the conversion of angiotensin I to angiotensin II by ACE

Question 11

Effect of ACEi?

Answer 11

ACE inhibitors reduce the AT1 dependent vasoconstriction leading to a fall in TPR and a fall in blood pressure

It also reduces the production of aldosterone meaning that you get a decrease in blood volume and a decrease in venous return

Question 12

How do ACEi effect cardiac output

Answer 12

It also reduces the production of aldosterone (which retains water and Na) meaning that you get a decrease in blood volume and a decrease in venous return

The venous return is also linked, by Starling's Law, to contractility (and cardiac output)

Reduced venous return reduces the cardiac output because of the decrease in preload 

So as anti‐hypertensives, ACE inhibitors have an effect on TPR and cardiac output

Question 13

What do AT receptor blockers do?

Answer 13

Antagonists of receptors for ATII

Question 14

Main unwanted effect of ACEi? Why?

Answer 14

Cough because it prevents the breakdown of bradykinin which causes cough

Question 15

Unwanted effects of ACEi (4)

Answer 15

Cough, hypotension, hyperkalaemia, renal failure

Question 16

how does ACEi cause hyperkalaemia

Answer 16

because there is less sodium reuptake and less potassium excretion. Aldosterone promotes insertion of Na channels and NaK ATPase into kidney cells to promote Na moving from the tubule into the blood. If you block AT1 receptor, or block ACE, less aldosterone and so fewer of these proteins in the membrane. This means that there is an increased K in the blood as it isn’t lost in the urine. Also may cause hyponatraemia.

Question 17

How can ACEi cause renal failure

Answer 17

You get poor flow into the glomerulus with poor pressure so GFR isn’t great. ATII one of its roles is to constrict the efferent arteriole and so increase the pressure in the glomerulus. But if you give patients ACEI or ARB you lose the ability to constrict the efferent arteriole so low pressure in glomerulus, GFR goes down, renal failure carries on from there.

Question 18

Dihydropyridines AKA

Answer 18

Non-rate limiting

Question 19

Dihydropyridines were more powerful on va. SM or cardiac SM?

Answer 19

va. SM

Question 20

Are dihydropyridines/non-dyhydropyridine OR rate-limiting/non-rate limiting CCBs used more for hypertension

Answer 20

Dihydropyridines/ non-rate limiting bc they don’t limit heart rate

Question 21

Are CCBs lipid soluble

Answer 21

Not very

Question 22

Where do CCBs act

Answer 22

extracellular surface of the protein

Question 23

What do DHP do regarding Ca

Answer 23

inhibit calcium entry into vascular smooth muscle cells

Question 24

What can the decreased blood pressure due to DHP cause

Answer 24

reflex tachycardia

Question 25

What effect can vasodilators have on myocardial oxygen demand and why

Answer 25

powerful vasodilators can lead to reflex tachycardia and increased inotropy thus increased myocardial oxygen demand

Question 26

Why give anyone over 55 or Afro Caribbean CCBs or thiazide diuretic

Answer 26

these groups tend to have low renin hypertension. This means that their plasma renin is low relevant to aldosterone and ATII levels, and because of this an ACEI doesn’t have the same effect

Question 27

where do BB have their main effect

Answer 27

Heart

Question 28

Why have BBs been removed as first line treatment for hypertension

Answer 28

Reduction in TPR has the most profound effect on blood pressure and beta blockers have their main effect on the heart

Question 29

Why are alpha blockers used as antihypertensives

Answer 29

If you block the alpha 1 receptor in vasculature you get profound vasodilation and a drop in total peripheral resistance

Question 30

Problem with with alpha blockers?

Answer 30

Selectivity, you need a relatively selective alpha‐1 blocker because the alpha-2 receptor is the negative feedback receptor for the SNS
you need a relatively selective alpha‐1 blocker because the alpha-2 receptor is the negative feedback receptor for the SNS

Question 31

what is spironolactone

Answer 31

Aldosterone Antagonist

Question 32

An Aldosterone Antagonist ?

Answer 32

Spironolactone

Question 33

3 main treatments for cardiac failure

Answer 33

ACE Inhibitors
Beta Blockers
Angiotensin Receptor Blockers