3.A-RAAS Inhibitors Flashcards
What are the major hormone products of the RAAS?
angiotensin II
aldosterone
How is angiotensin II derived?
angiotensinogen–>angiotensin I (via renin)
angiotensin I–>angiotensin II (via ACE)
What are the major actions of angiotensin II?
rapid pressor response (vasoconstriction)
slow pressor response (kidney specific effects)
vascular and cardiac hypertrophy and remodelling (effects on heart tissue)
What are the consequences of low pressure to the kidney?
decreased filtration
decreased excretion of toxic substances
decreased tubular pressure–>collapse–>acute renal failure
Which cells release renin?
juxtaglomerular cells
What are the 3 pathways which release renin?
intra-renal baroreceptors (low renal pressure)
macula densa (low Na in the loop)
B1 adrenergic receptor pathway (SNS activation)
What is the binding site for renin?
angiotensinogen
Where would you find ACE?
all over the body on endothelial cell surfaces (angiotensin I to II is automatic in many tissues/organs)
What are the effects of angiotensin II on reno-vascular tissue?
vasoconstriction in several tissues
in the kidney it constricts efferent arterioles
-increases glomerular pressure forcing more fluid to be
filtered
-results in rapid increase in GFR
How is aldosterone released?
released from adrenal gland following stimulation of the angiotensin-type 1 receptor (AT1) by ANG II
Where does aldosterone bind?
aldosterone receptors in cells of the distal tubule/collecting tubule
What are the actions of aldosterone?
reabsorption of Na and excretion of K
-increased activity of ENaCs
-increased synthesis of ENaCs
What is the main mineralocorticoid hormone of the body?
aldosterone
What are ACE inhibitors and where do they act?
inhibit ACE activity (ANG I to ANG II conversion)
occurs on endothelial cells throughout circulation
True or false: many ACE inhibitors are prodrugs and are not very potent but have good oral bioavailability
true
What do all ACE inhibitors end in?
-pril
What are the uses of ACE inhibitors?
high blood pressure
-vasodilation and decreased aldosterone secretion
chronic kidney disease
-decreased renal pressure
heart failure and ischemic heart disease
-decreased adverse effects of ANG II and aldosterone on heart
tissue and blood vessels
What are some cautions with ACE inhibitors?
reduced blood pressure
dry cough (bradykinin accumulation)
risk of hyperkalemia (aldosterone inhibition)
decreased renal perfusion in vulnerable patients
What do ARBs stand for?
angiotensin receptor blockers
Where do ARBs act?
inhibit the AT1 receptor (thus blocking actions of ANG II)
True or false: the actions of ARBs differ from ACE inhibitors
cap
they both block ANG II induced vasoconstriction and aldosterone release (except ARBs have much lower cough due to degradation of bradykinin)
What do all ARBs end in?
-sartan
What are the first line blood pressure agents for people with chronic kidney disease?
ACE inhibitors and ARBs
What are some of the effects of declined kidney function due to damage?
decreased GFR
increased serum creatinine
difficulties excreting fluid and toxins
leakage of proteins
How do DRI agents work?
bind to the active site of renin to prevent the angiotensinogen to ANG I conversion from happening
What is the name of the only DRI available in Canada?
aliskiren
What do MRAs stand for?
mineralocorticoid receptor antagonist
How do MRAs work?
inhibit the aldosterone receptor
What are the names of the MRAs?
spironolactone
eplerenone
True or false: MRAs are very effective blood pressure agents
cap
What are the uses for MRAs?
resistant hypertension due to aldosterone excess
heart failure (block -ve effects of aldosterone on heart)
What are some cautions with MRAs?
increased potassium
hormonal effects (partially stimulates progesterone and androgen receptors)
What is RAAS?
renin-angiotensin-aldosterone system
system that increases blood pressure
RAAS over-activity occurs in many CV conditions
What is the major determinant of RAAS activation?
renin
Where is aldosterone synthesized?
synthesized and released from the adrenal gland following stimulation of the AT-1 receptor by ANGII
How does aldosterone counteract diuretics?
aldosterone promotes the re-absorption of Na while diuretics try inhibit the re-absorption of Na
True or false: aldosterone is the only hormone made in the adrenal gland
false
the adrenal gland also makes cortisol and dehydroepiandrosterone
Aside from ACE, which other enzyme is inhibited by ACE inhibitors?
kininase II
What does long-standing hypertension increase risk for (in regards to kidney)?
chronic kidney disease
-increased pressure can damage glomerulus, damaging filter
function
When is ACEI and ARB use considered to be risky?
vulnerable people (poor renal blood flow)
-dehydrated
-renal artery stenosis
What is a major contraindication for ACEI and ARBs?
renal artery stenosis
