Exam 2 lecture 6 Flashcards
BP formula
CO X PR
cardiac output x peripheral resistance
what are two direct effects of NE
On heart- Increase HR
on kidney- Renin release (RAAS)
How does renin release affect BP
Rennin release can affect BP
what receptors does NE act on in the heart.
B-1 receptors
Renin inhibitor stops what step
Angiotensinogen to angiotensin I
ACE inhibitor stops what step
Angiotensin I to angiotensin II
How does B1 activation affect CO
increases it
do RAAS blockers affect BV and SV?
yes
why do alpha blockers matter for SV
they reduce peripheral resistance
How is renin release activated in the kidney
When we have low Na or low BP
Where is ACE released from
Lungs
Where is angiotensinogen released from
Liver
What does aldosterone secretion do
Increase Na retention
How does angiotensinogen affect BP
increases it
What is renins substrate
angiotensinogen
What is the product for Renin and angiotensinogen
angiotensin I
What kind of molecule is Angiotensin I? What is it a substrate for?
Angiotensin I is a peptide.
Angiotensin I is a substrate for ACE
What does ACE do to Angiotensin I
Converts it to Angiotensin II
What are the two targets for Angiotensin II
1) Producing vasoconstriction, increasing BP
2) aldosterone secretion, increasing NA and H20 retention, increasing BP
What do ACE inhibitors target? WHat do ARBs target?
ACE inhibitor targets ACE
ARBs target Angiotensin II
ARB acronym. WHat does it block
Angiotensin receptor blcoker. Blocks Angiotensin II
Additional action of ACE
Works on bradykinin
Is bradykinin active? Is Angiotensin I active
ANgiotensin I is inactive and Angiotensin II is actove. ACE inhibitors stop the activation of angiotensin I
Bradykinin is active. ACE cleavs it and makes it inactive. ACE makes it inctive. ACE inhibitors keep t active
Bradykinin use
Goes through prostaglandin to cause vasodilation
How does ACE affect bradykinin
When ACE deactivates bradykinin, it blocks vasodilation. Causing vasocinstriction and increasing BP.
ACE inhibitors stop this inactivation of bradykinin
What causes and stops angiotensinogen to angiotensin
Renin causes it
Renin inhibitors stop it
What causes and stops angiotensin I to angiotensin II
ACE causes
ACE inhibitors stop
ACE inhibitor drug names end in
-pril
Name some ACE inhibitor drugs
Benzapril
Captopril
Enalapril
Lisinopril
Ramipril
What blocks angiotensin II to aldosterone
ARB
Name ARB drugs
-sartans
Losartan
candesartan
Valsartan
irbesartan
What blocks aldosterone reaching target cell
aldosterone antagonist (spironolactone)
What cells release renin
Juxtaglomerular cells in kidney
How is angiotensinogen degraded
angiotensinogen->angiotensin I->angiotensinII->angiotensin III.
Angiotensin III is the inactive product
name a renin inhibitor drug
Aliskiren
Aliskiren MOA
It is a renin inhibitor that stops formation of ANG I from angiotensinogen
What is a contraindication for all RAAS drugs (renin inhibitors, ACE inhibitors, ARBs)
Pregnant and nursing
Ace inhibitor drugs all end in
-Pril
What is the most potent ACE inhibitor
Enalapril
What is something all ACE inhibitors share in common with each other
They are prodrugs (except lisinopril)
What are the 3 ACE inhibitor classes
Sulfhydryl containing
Dicarboxyl containing
Phosphorous containing
Sulfhydryl containing ACE inhibitor prototype
Captoptril
Dicarboxyl containing ACE inhibitor prototype
enalapril
Phosphorous containing ACE prototype
Fosinopril
Most commonly used ACE inhibitor
Lisinopril
Which ACE inhibitor is not a prodrug
Lisinopril
What is enalaprils name when active? ROA? Prodrug or not?
Enalaprilat
Oral and IV
Prodrug
Captoptril pro drug or no? side effects?
Not pro drug
may cause rashes
How can we tell if an ACE inhibitor is active or a prodrug from a structure
If the structure has two carboxylate groups, it is ACTIVE
How is enalapril activated? How can we tell the structure apart
Esterase cleaves it and activates it.
has ester group and carboxylic acid group
How can we differentiate captopril structurally
sulfohydryl (HS group)
How can we tell fosinopril apart from the other ACe inhibitors
Has phosphate group
What do ACE inhibitors do
Reduce vasoconstriction and reduce myocardial mitogenic actovity
1st line tx for HTN
ACE and ARB
Demographics of who ACE inhibitors and ARBs could benefit most
Works least on african american
ACE inhibitors side effects
Dry cough, Angioedema, hyperkalemia
NSAID and ACE inhibitor inhibitor worry
NSAIDs may lower effectiveness
Why is cough and angioedema a side effect for ACE inhibitors but not ARBS (AT1)
Cough and angioedema caused by bradykinin pathway. ARBs do not affect this pathway.
how do NSAIDs affect ACE inhibitors
NSAIDs block the production of prostaglandins. This lowers the hypotensive effect of ACE
ARBs all end with? also known as
-SARTANS
AT1 receptor blockers
MOA of ARBs
Block angiotensin I receptors with a much higher affinity for AT1 versus AT2
Are ARBs more selective for AT1 or AT2
AT1
least potent ARB? most potent ARB?
least- losartan
most- candesartan and omesartan
Main ARBs
Losartan and Valsartan
Recognize the ARB scaffold
phenyl ring attatched to imidazoline
How to differentiate Valsartan and Losartan structurally
Valsartan has an Isopropyl group (looks like a V)
Losartan has an OH group (LOHsartan)
T/F Even though losartan is the least potent ARB, Losartans metabolite is as potent as valsartan
True
in what order do we try ACE and ARBs
ACE 1st, then ARB
Clinical use of ARBs
HTN 1st line, use if ACE do not work or are not tolerated
Adverse effects of ARBs? COntraindicated in
Hyperkalemia
pregnant and nursing women (just like the other RAAS drugs)
ARBs and ACEs do not work well in african americans yes or no
True
Aldosterone MOA and drug bnames
Spironolactone and eplerone
MOA
-potassium sparring diuretic
adverse effects of spironolactone
Hyperkalemia
Gynecomastia
1st line drugs for HTN
Diuretics (thiazides)
ACE inhibitors
ARBs
CCBs
In no particular order
2nd line drugs for HTN
Loop diuretics
sympatholytics (B and A blockers)
Direct renin inhibitor
Two thiazide drugs
Chlorthalidone
Hydrochlorothiazide
Where do thiazides work? what transorter does it use?
DCT
Uses Na-CL transporter
Do thiazides work well in african americans?
Good for AFrican americans
Not good for diabetes patients
Side effects of Thiazides
Hyperkalemia, Hyperuremia, Hypercalcemiia
Why are loop diuretics not 1st line?
Single doses are potent but very short acting
Drugs to avoid in pregnancy
ACE inhibitors
ARBs
Direct renin inhibitors
Aldosterone antagonists
B blocker end with
Alpha blockers end with
ACE inhibitors end with
Angiotensin II receptors end with
B blockers- LOL
Alpha blockers-AZOSIN
ACE inhibitors- PRIL
ARBs- SARTAN
renin inhibitor drug name
Aliskiren
Aldosterone drugs
Spironolactone
Epelrone
Thiazide drug name
Chlorothalidone
Hydrochlorothiazide
Alpha 2 agonist drug names
Clonidine
Methyldopa
Dopamine receptor agonist drug name
Fenoldopam
