Pharmacology - ACE inhibitors + ARBs Flashcards
____ releases angiotensinogen
____ releases renin
what is the relationship between the 2?
liver produces angiotensinogen
kidney produces renin
renin is the enzyme that converts angiotensinogen into angiotensin I
what does aldosterone do
leads to sodium and water retention and decreased potassium
fluid retension causes increased BP
corticosteroids ____ the production of angiotensinogen
increase
renin is secreted in response to what 3 things
-decrease in arterial BP
-decreased sodium
-increased sympathetic NS activity
TO INCREASE BP BY CONVERTING ANGIOTENSINOGEN INTO ANGIOTENSIN 1
____ stimulates aldosterone secretion from the adrenal cortex
angiotensin II
causing increased BP
____ is a potent vasoconstrictor which leads to increased BP
angiotensin II
***ACE inhibitors reverse………
cardiac and vascular hypertrophy and remodeling
**______ reverse cardiac and vascular hypertrophy and remodeling
ACE inhibitors
3 bad effects of angiotensin II
high BP
myocardial infarction
renal damage
true or false
ACE inhibitors decrease peripheral resistance
TRUE
by blocking vasoconstriction caused by angiotensin II
***major side effect of ACE inhibitors
explain how it happens
COUGH
bc bradykinin and substance P breakdown is INHIBITED in the lungs
true or false
ARBS do not cause the side effect of cough seen in ACE inhibitors
true
what do ACE inhibitors do to potassium levels
increase potassium levels
**true or false
enalapril is a prodrug
TRUE
active form is enalaprilat
what is the advantage of enalapril over captopril
less side effects
***true or false
ramipril is not a prodrug
FALSE - it is
which ACE inhibitor is tissue specific and thus protective of the heart and kidney?
ramipril
***true or false
lisinopril is not a prodrug
TRUE - not a prodrug
**TRUE OR FALSE
fosinopril is not a prodrug
FALSE - it is
active form is fosinoprilat
***which medication has beneficial effects for patients with hypertension and left ventricular hypertrophy and why?
FOSINOPRIL
it produces adequate blood pressure reduction and reversal of the hypertrophy
true or false
ACE inhibitors are considered first line for hypertension
TRUE
true or false
ACE inhibitors do not cause hyperuricemia like diuretics do
true
explain the MOA of ARBs
they block the angiotensin II RECEPTOR (AT I receptor) and thus prevent angiotensin II from binding to it and exerting its effects of vasoconstriction
what does angiotensin II do to urine output?
decreases urine output and decreased GFR
where is the AT 1 receptor expressed
in the heart and blood vessels
where is the ACE enzyme released from
the lungs
through what kind of receptor do AT1 receptors work
the phospholipase C-IP3/DAG intracellular calcium type – Gq!!!!!
incresed calcium causes vasoconstriction and muscle contraction - thereby increasing BP when angiotensin II binds
WHAT IS THE SPECIFIC AT1 BLOCKER
Losartan
true or false
ARBS block AT2 more than AT1
FALSE - AT1 more than AT2
**___ AND ___ were the first marketed blockers of the angiotensin II type 1 (AT1) receptor
losartan and valsartan
explain the pharmacology of losartan
competiive?
agonist?
what receptor?
competitive antagonist and inverse agonist of the AT1 receptor
meaning it either binds and has NO EFFECT or binds and does the OPPOSITE EFFECT (vasodilation)
true or false
losartan inhibits ACE
FALSE
give 3 reasons why we need ARBs over ACE inhibitors
ARBS do not have the persistent cough side effect
(VERY rarely if they do)
completely inhibiting AT1
indirectly activate AT2 and cause vasodilation! additional benefit
true or false
losartan can be used in pregnancy
FALSE
ACE inhibitors and ARBS are not safe in pregnancy
true or false
valsartan is selective for AT1
TRUE
true or false
valsartan is a noncompetitive inhibitor of angiotensin II
FALSE - competitive inhibitor
___ causes the release of aldosterone from the adrenal cortex of the kidney
what is the effect of this
angiotensin II
causes water and sodium retention and thus increased BP
name 2 side effects of valsartan
hypotension
dizziness
name 2 side effects that are more common in ACE inhibitors than ARBS
angioedema
cough
what do ARBS do to potassium levels
increased
*****name an ARB that is metabolized by CYP3A4
losartan
***name an ARB that is metabolized by CYP2C9
irbesartan
name an ARB that has low liver metabolism
valsartan
**true or false
candesartan is a prodrug
TRUE
activated in GI by esterases through hydrolysis
**true or false
azilsartan is not a prodrug
FALSE - it is
____ has an ability to remain tightly bound to ATI receptors for very long periods after drug washout
azilsartan
not good
what CYP is azilsartan metabolized by
CYP2C9
WHICH ARB HAS THE STRONGEST RECEPTOR BINDING AFFINITY IN THE ENTIRE CLASS???
TELMISARTAN
which ARB has the longest half life and highest lipophilicity
telmisartan
which ARB is good for patients with diabetes and why?
telmisartan
bc it can improve insulin sensitivity and help with hypertension
additive PPARy agonistic action
true or false
ARBS can cause decreased potassium
FALSE increase
what do ARBS do to lithium levels
increase - bc it follows potassium
what class of drugs decreases the effect of ARBs
NSAIDS
bc they cause sodium retension
recap - how do spironolactone and eplerenone decrease BP
bc they antagonize aldosterone
aldosterone would normally cause sodium and water retention and thus increase BP
