vascular system

Question 1

step 1 hypertension treatment for under 55s

Answer 1

ACE inhibitor or angiotensin receptor blocker (ARB)

Question 2

step 1 hypertension treatment for over 55s or afro-Caribbean’s

Answer 2

Ca2+ channel blocker (CCB) or thiazide-like diuretic

Question 3

step 2 hypertension treatment

Answer 3

CCB or thiazide-like diuretic and ACE inhibitor or ARB

Question 4

step 2 hypertension treatment for afro-Caribbean’s

Answer 4

same, but ARBs preferred to ACE inhibitors

Question 5

step 3 hypertension treatment

Answer 5

combination of ACE inhibitor/ARB with CCB and thiazide-like diuretic

Question 6

step 4 resistant hypertension treatment

Answer 6

low dose spironolactone, B-blocker or a-blocker

Question 7

2 reactions ACE inhibitors prevent

Answer 7

angiotensin I -> angiotensin II; bradykinin -> inactive metabolites

Question 8

3 stimuli for renin

Answer 8

decreased renal Na+ reabsorption, decreased renal perfusion pressure, increased SNS

Question 9

4 normal angiotensin II actions

Answer 9

SNS activation and thirst, vasoconstriction, direct salt and water retention, aldosterone secretion (indirect salt and water retention)

Question 10

6 uses of ACE inhibitors

Answer 10

hypertension, heart failure, post-myocardial infarction, diabetic nephropathy, progressive renal insufficiency, patients at high risk of cardiovascular disease

Question 11

example of ACE inhibitor

Answer 11

enalapril (usually -pril)

Question 12

what will ACE inhibitors help treat by decreasing TPR and venous return

Answer 12

hypertension and heart failure

Question 13

how do increased TPR and increased venous return worsen hypertension

Answer 13

increased TPR directly contributes to increased BP, and increased venous return leads to increased cardiac contractility (via Starling’s Law), and thus cardiac output and BP

Question 14

how do increased TPR and increased venous return worsen heart failure

Answer 14

increased vasoconstriction increases afterload and cardiac work, and increased venous return leads to long term fluid retention and congestion, leading to oedema

Question 15

example of ARB

Answer 15

iosartan

Question 16

mechanism of ARB action

Answer 16

antagonist of type 1 (AT1) receptors for angiotensin II, preventing renal and vascular actions of angiotensin II (same outcome as ACE inhibitors)

Question 17

2 uses of ARB

Answer 17

hypertension, heart failure (same as ACE inhibitors)

Question 18

are ACE inhibitors and ARB well tolerated

Answer 18

yes, particularly ARB

Question 19

3 side effects of both ACE inhibitors and ARB

Answer 19

hypotension (e.g. dizziness, postural), hyperkalaemia, renal failure in patients with renal artery stenosis

Question 20

how do ACE inhibitors and ARB cause renal failure in patients with renal artery stenosis

Answer 20

angiotensin II controls pressure in glomerulus (constricts efferent arteriole, increasing pressure), so if pressure falls then can’t regulate glomerular filtration pressure

Question 21

side effect of just ACE inhibitors and why

Answer 21

build up of bradykinin so cough

Question 22

how do ACE inhibitors and ARB cause hyperkalaemia

Answer 22

by stopping Na+ reabsorption to lower blood volume, K+ exchange is not occuring so builds up in blood

Question 23

how is hyperkalaemia cared with

Answer 23

K+ supplements or K+ sparing diuretics

Question 24

process of smooth muscle contraction

Answer 24

membrane depolarisation opens VGCC -> Ca2+ enters -> binds to calmodulin (CaM) -> Ca2+-CaM complex binds to and activates myosin light chain kinase (MLCK) -> MLCK mediated phosphorylation -> smooth muscle contraction

Question 25

2 classes of Ca2+ channel blockers

Answer 25

dihydropyridines, non-dihydropyridines (rate-limiting)

Question 26

uses of dihydropyridine Ca2+ channel blockers

Answer 26

hypertension, prophylaxis of angina, as more selective for blood vessels

Question 27

example of dihydropyridine Ca2+ channel blocker

Answer 27

amiodipine

Question 28

example of non-dihydropyridine Ca2+ channel blocker

Answer 28

verapamil

Question 29

what doesn't amiodipine cause in heart, which verapamil does

Answer 29

negative inotropy

Question 30

how do dihydropyridine Ca2+ channel blockers treat hypertension

Answer 30

inhibit Ca2+ entry into VSMCs, decreasing TPR and BP

Question 31

side effect of using dihydropyridine Ca2+ channel blockers to treat hypertension

Answer 31

powerful vasodilation can lead to reflex tachycardia and increased inotropy, thus increasing myocardial oxygen demand

Question 32

how are anti-hypertensives selected for treatment

Answer 32

based on compliance (usually due to side effects); select CCB or thiazide-type diuretic (e.g. afro-Caribbeans) because of low plasma renin activity; evidence of effects on heart failure, stroke, death etc.

Question 33

drugs for hypertension: RAS inhibitors vs CCBs outcomes on SBP, heart failure, stroke and all-cause death

Answer 33

CCBs decrease SBP more than RAS inhibitors, RAS inhibitors decrease heart failure but increase stroke, with no difference for all-cause death

Question 34

drugs for hypertension: RAS inhibitors vs thiazides outcomes on SBP, heart failure, stroke and all-cause death

Answer 34

thiazides decrease SBP more than RAS inhibitors, RAS inhibitors increase heart failure and stroke; no difference for all-cause death

Question 35

drugs for hypertension: RAS inhibitors vs B-blockers outcomes on SBP, CV events, stroke and all-cause death

Answer 35

no difference in SBP reduction, RAS inhibitors decrease CV events and stroke; no difference for all-cause death

Question 36

why might a1-adrenoceptor antagonists e.g. prazosin be used as anti-hypertensives

Answer 36

a1 adrenoceptors cause vasoconstriction, so this is blocked, lowering TPR