Block 3: RAAS
Terms
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- go from angiotensinogen to angiotensin II
- angiotensinogen -> (renin) -> angiotensin I -> (ACE chymase) -> angiotensin II
-
At what receptor does angiotensin II cause
1. Na and fluid retention
vasoconstriction
sympathetic activation
cell growth
aldosterone secretion - AT1
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at what receptor does angiotensin II cause
vasodilation
cell growth inhibition
apoptosis - AT2
- Name four classes of drugs that act on the RAAS
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1. renin inhibitors
2. ACE inhibitors (captopril and enaapril)
3. ARBs (losartan) (stops angiotensin II from progressing to AT1)
4. MR antagonists (spironolactone and eplerenone) (stops aldosterone from acting on Mineralocorticoid receptors) - Name two ACE inhibitors
-
captopril
enalapril - Are ACE inhibitors less effective in black patients or white patients
- black patients
- In what population/indication is an ACE inhibitor better than a diuretic/beta-bolocker antihypertensive treatment regimen
- preventing cardiac vascular events (MI, stroke) in hypertensive diabetic patients
- if ACE inhibitors don't work on the heart, how do they improve the clinical and hemodynamic state of CHF patients
- they relax vascular smooth muscle (arterial and venous)
- are ACE inhibitors helpful in patients with acute MI
- yes
- Are ACE inhibitors helpful in reducing the rates of death, MI, stroke, cardiac arrest, heart failure, and/or complications of diabetes ONLY in the presence of left ventricular dysfunction
- no- they can help even in the absence of left ventricular dysfunction
- What did the HOPE vs. PROGRESS trial show
- ACE inhibitors show 32% relative risk reduction in stroke
- What did the HOPE vs. PEACE clinical trial show
- ACE inhibitors have a use in stable CAD
- Name four contraindications for ACE inhibitors
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renal artery stenosis
elevated potassium (>5.5)
symptomatic hypotension
pregnancy - Name 6 side effects of ACE inhibitors
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severe hypOtension
chronic non-productive Cough
dysgeusia (Taste problems)
Renal hemodynamic dysfunction
hyperkalemia
Angioedema
Proteinuria
Pregnancy problems
Rash
Lower Angiotensin II
CAPTOPRIL - What interaction occurs between ACE inhibitors and NSAIDS
- reduced ACE inhibitor antihypertensive effect
- What interaction occurs between digoxin and ACE inhibitors
- reduced digoxin clearance
- What interaction occurs between K supplements or K sparing diuretics and ACE inhibitors
- hyperkalemia
- What interaction occurs between thiazide or loop diuretics and ACE inhibitors
- enhanced hypotensive effect
- Name an ARB drug
- losartan
- what is losartan's MOA
- AT1 antagonist -> interferes with angiotensin II binding to AT1
- Would losartan be less effective in black patients or white patients
- black patients
- when would you use losartan as monotherapy for hypertension
- in patients who can't tolerate ACE inhibitors
- Does losartan cause cough or angioedema
- no
- What did the CHARM study show
- that losartan reduces CV mortality and hospital admissions in patients with left ventricular dysfunction when substituted for ACE inhibitors
- What did the VALIANT study show
- that losartan reduces morbidity and mortality after MI
- What did the ACCESS study show
- losartan reduces mortality and cardivascular events after stroke
- Name four contraindications for losartan
-
renal artery stenosis
elevated serum K
symptomatic hypotension
pregnancy
(just the same as ACE inhibitor contraindications) - Name two aldosterone receptor antagonists
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spironolactone
eplerenone -
this drug is a potassium sparing diuretic
an aldosterone receptor antagonist
weak androgen antagonist
and progesterone receptor agonist - spironolactone
- this drug is a K sparing diuretic, a selective aldosterone receptor blocker with less affinity for androgen, progesterone, and glucocorticoid recptors than spironolactone
- eplerenone
- this is a mineralocorticoid hormone produced in the adrenal cortex and in extra-adrenal sites whose synthesis and secretion are affected by angiotensin II, K levels, ACTH and other stimuli
- aldosterone
- Name four sites of aldosterone receptors
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kidney
brain
heart
blood vessels - What does aldosterone do in the kidney
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1. stimulates sodium retention by distal nephrons,
2. K excretion,
3. blood volume expansion,
4. elevation of blood pressure - in patients with normal K and adequate renal function, with severe HF caused by LV dysfunction, what treatment should be considered
- low dose spironolactone
- What did the EPHESUS trial show
- eplerenone is helful in patients with LV dysfunction after MI
- Name two contraindications for aldosterone receptor antagonists (spironolactone and eplerenone)
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hyperkalemia
cirrhosis - What are unique side effects of spironolactone
- progestational and antiandrogenic effects- gynecomastia, impotence, menstrual irregularities
- What drug has an interaction with eplerenone and spironolactone
- digitalis (effects its clearance)
- Captopril or Enalapril inhibit the activity of ___ to reduce the formation of ___
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ACE
angiotensin II