PHARM 12: Drugs + CVS - VASCULATURE Flashcards
what is meant by vascular tone
when Arteriolar S.M. normally displays a state of partial constriction
link BP , TPR and CO in an equation
BP= CO x TPR
What is hypertension?
- blood pressure consistently above 140/90 mmHg
step 1: How would you treat Hypertension
- under 55s = Angiotensin converting enzyme (ACE) inhibitor OR angiotensin receptor blocker (ARB)
- over 55s or afro-Caribbean’s = Calcium channel blocker (CCB) or thiazide-like diuretic
step 2: How would you treat Hypertension
- CCB or thiazide-like diuretic + ACEi or ARB
- ARBs preferred to ACEi for AfroCaribbean’s
step 3: How would you treat Hypertension
- Combination of ACEi/ ARB with CCB and thiazide-like diuretic is recommended
step 4: How would you treat Hypertension
Resistant Hypertension:
- Consider low-dose spironolactone
- Consider beta-blocker or alpha blocker
how does RAS lead to hypertension?
i.e what can stimulate RAS ?
- decrease in renal Na+ reabsorption
- causes decrease in renal perfusion pressure
- increases SNS
how do ACE inhibitors work?
- they inhibit conversion of ATI –> AT II by ACE
- AT II = potent vasoconstrictor
give example of an ACE inhibitor
enalapril
When might be ACE inhibitors used?
- hypetension
- heart failure
- post myocardial infarction
diabetic nephropathy
progressive renal insufficiency
why would Increased TPR and venous return worsen heart failure/ hypertension?
- increased TPR –> increased vasoconstriction (BP) causes Increased BP
+ (HEART) increases after load –> increasing cardiac work - increased venous return -> (BP) causes increased cardiac contractility + CO (HEART) causes long term fluid retention + congestion –> leads to oedema
what are potential side effects of ACEi + ARB?
- Cough (ACEi)
- hypotension (both)
- fetal injury
- renal failure (if has renal artery stenosis)
- urticaria
- hyperkalaemia =
Whats the difference between Dihyropyridines (non rate limiting )
and Non DHPs (rate limiting)
- DHPS = more selective for blood vessels
Whats the difference between amlodipine and verapamil?
Amlodipine: does not cause any negative inotropy
verapamil: causes large -ve inotropic effect
so Amlodipine is better to use for hypertension
Which of the calcium channel blockers would you use to treat: Hypertension ?
DHPs (Amlodipine)
How would DHP work to treat hypertension?
- DHPs –> inhibit Ca2+ entry into vascular smooth muscle cells
- decrease in TPR + BP
N.B. Powerful vasodilation can lead to reflex tachycardia and
increased inotropy thus increased myocardial oxygen demand
How would alpha blockers work to treat hypertension?
alpha 1 –> causes vasoconstriction
if alpha 1 blocked –> causes vasodilation by reducing Ca2+ influx
peripheral reisistance is mainly driven by _________
arteriolar constriction
What are effects of AT II ?
- stimulates aldosterone production –> which promotes salt and water retention
- potent vasoconstrictor
- stimulates thirst
how would AT II receptor blockers treat heart failure?
- more vasodilation –> less force need to pump blood out of heart
- reduce salt and water retention –> decreases venous return
- venous return = preload –> drives CO
- decrease CO
note: can also decrease congestion of the heart
how would AT II receptor blockers treat hypertension?
- reduce vasoconstriction
- reduce salt and water retention –> decreases venous return
- venous return = preload –> drives CO
- decrease CO
–> causes decrease in BP
why does ACEi cause cough as a side effect?
ACEi –> prevents break down of bradykinin
which accumulates and initiates cough
why does ACEi cause hyperkalaemia as a side effect?
aldosterone promotes insertion of Na-K atlases into kidney cells
if you block ACE - you get less aldosterone
so you get less channels
so teure is less uptake of K+ –> into kidney cells
so there is an increase in accumulation of K+ in the blood
results in hyperkalaemia
- why does ACEi cause renal failure (if has renal artery stenosis)
- people with renal failure
have a low GFR
angiotensin –> constricts the afferent arteriole –> and increases the pressure of the glomerulus –> which improves the GFR
However
but if this is inhibited –> the ability to vasoconstrictor the afferent article is lost –> so there is low pressure in the glomerulus –> which causes renal failure
describe the process of normal smooth muscle contraction
- memb depolarization open s VGCC
Ca2+ enters a+ binds to Calmodulin (CAM) - Ca-CAM complex binds to and activates MLCK
- MLCK mediated phosphorylation –> causes smooth muscle contraction
elderlies + afro carribeans –> you give CCB as 1st step hypertensive.
Why?
a) because tends to have low renin hypertension
- they would have low plasma renin
- so ACEi –> has less of an effect
- and so you would require too much dose
b) older you get the more dependent BP gets on atherosclerosis rather than RAS
so ACEi –> would have less of an effect
