vascular system Flashcards
vasoactive drugs: identify the drugs that impact vascular tone, their mechanisms of actions and their side-effects
step 1 hypertension treatment for under 55s
ACE inhibitor or angiotensin receptor blocker (ARB)
step 1 hypertension treatment for over 55s or afro-Caribbean’s
Ca2+ channel blocker (CCB) or thiazide-like diuretic
step 2 hypertension treatment
CCB or thiazide-like diuretic and ACE inhibitor or ARB
step 2 hypertension treatment for afro-Caribbean’s
same, but ARBs preferred to ACE inhibitors
step 3 hypertension treatment
combination of ACE inhibitor/ARB with CCB and thiazide-like diuretic
step 4 resistant hypertension treatment
low dose spironolactone, B-blocker or a-blocker
2 reactions ACE inhibitors prevent
angiotensin I -> angiotensin II; bradykinin -> inactive metabolites
3 stimuli for renin
decreased renal Na+ reabsorption, decreased renal perfusion pressure, increased SNS
4 normal angiotensin II actions
SNS activation and thirst, vasoconstriction, direct salt and water retention, aldosterone secretion (indirect salt and water retention)
6 uses of ACE inhibitors
hypertension, heart failure, post-myocardial infarction, diabetic nephropathy, progressive renal insufficiency, patients at high risk of cardiovascular disease
example of ACE inhibitor
enalapril (usually -pril)
what will ACE inhibitors help treat by decreasing TPR and venous return
hypertension and heart failure
how do increased TPR and increased venous return worsen hypertension
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
how do increased TPR and increased venous return worsen heart failure
increased vasoconstriction increases afterload and cardiac work, and increased venous return leads to long term fluid retention and congestion, leading to oedema
example of ARB
iosartan
mechanism of ARB action
antagonist of type 1 (AT1) receptors for angiotensin II, preventing renal and vascular actions of angiotensin II (same outcome as ACE inhibitors)
2 uses of ARB
hypertension, heart failure (same as ACE inhibitors)
are ACE inhibitors and ARB well tolerated
yes, particularly ARB
3 side effects of both ACE inhibitors and ARB
hypotension (e.g. dizziness, postural), hyperkalaemia, renal failure in patients with renal artery stenosis
how do ACE inhibitors and ARB cause renal failure in patients with renal artery stenosis
angiotensin II controls pressure in glomerulus (constricts efferent arteriole, increasing pressure), so if pressure falls then can’t regulate glomerular filtration pressure
side effect of just ACE inhibitors and why
build up of bradykinin so cough
how do ACE inhibitors and ARB cause hyperkalaemia
by stopping Na+ reabsorption to lower blood volume, K+ exchange is not occuring so builds up in blood
how is hyperkalaemia cared with
K+ supplements or K+ sparing diuretics
process of smooth muscle contraction
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
2 classes of Ca2+ channel blockers
dihydropyridines, non-dihydropyridines (rate-limiting)
uses of dihydropyridine Ca2+ channel blockers
hypertension, prophylaxis of angina, as more selective for blood vessels
example of dihydropyridine Ca2+ channel blocker
amiodipine
example of non-dihydropyridine Ca2+ channel blocker
verapamil
what doesn’t amiodipine cause in heart, which verapamil does
negative inotropy
how do dihydropyridine Ca2+ channel blockers treat hypertension
inhibit Ca2+ entry into VSMCs, decreasing TPR and BP
side effect of using dihydropyridine Ca2+ channel blockers to treat hypertension
powerful vasodilation can lead to reflex tachycardia and increased inotropy, thus increasing myocardial oxygen demand
how are anti-hypertensives selected for treatment
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.
drugs for hypertension: RAS inhibitors vs CCBs outcomes on SBP, heart failure, stroke and all-cause death
CCBs decrease SBP more than RAS inhibitors, RAS inhibitors decrease heart failure but increase stroke, with no difference for all-cause death
drugs for hypertension: RAS inhibitors vs thiazides outcomes on SBP, heart failure, stroke and all-cause death
thiazides decrease SBP more than RAS inhibitors, RAS inhibitors increase heart failure and stroke; no difference for all-cause death
drugs for hypertension: RAS inhibitors vs B-blockers outcomes on SBP, CV events, stroke and all-cause death
no difference in SBP reduction, RAS inhibitors decrease CV events and stroke; no difference for all-cause death
why might a1-adrenoceptor antagonists e.g. prazosin be used as anti-hypertensives
a1 adrenoceptors cause vasoconstriction, so this is blocked, lowering TPR
