Hypertension - Lecture 2 (RAAS Drugs) Flashcards
Most patients with essential HTN have a normal Cardiac output but…
increased peripheral resistance
Drugs that target inappropriately high renin release?
ACEi
ARBs
Aldosterone Antagonists
Renin Inhibitors
Drug that target inappropriately high sympathetic outflow?
a-2 agonist
a-1 antagonist
B-blocker
Drugs that target increased Systemic resistance?
CCBs
Direct Vasodilators
Drugs that target abnormal renal salt/water handling?
Thiazide
K-sparing
Loop diuretics
Primary factors determining blood pressure?
RAAS
Sympathetic nervous system
Plasma volume (mediated by kidneys)
Excess stimulation of RAAS can lead to….
increase sympathetic activity
increased PVR
water/salt retention
All leads to increase BP
Targets for RAAS Drugs
Renin
ACE
AT1
Aldosterone
How do RAAS inhibiting agents lower BP?
via decreased PPR
all work to decreasing activity of Angiotensin II
ACEi MOA
block conversion of AT1-AT2 via ACE enzyme
ACEi effect on bradykinin
Will cause increase
Leads to cough and angioedema (rare)
Enalapril (Vasotec) Dosage and Frequenecy
5-40 mg, 1-2 times daily
Lisinopril (Prinivil, Zestril) Dosage and Frequency
10-40 mg, once daily
What to monitor in ACEi?
BP
K
ScCr
BUN
Are ACEi considered 1st line without compelling indication?
Yes
Benefits of ACEi in someone with vasculature issues?
It improves the vasculature
Helps improve blood vessel health and less likely to have that 2nd HA,Stroke, etc
Compelling use of ACEi?
Post-MI, HFrEF, ppl with ASVD risk
Renal protection for patients with protein related DM DKD or CKD
Contraindications of ACEi?
Pregnancy
Bilateral renal artery stenosis
avoid in women during childbearing years
ACEi efficacy in black patients
less efficacy as mono therapy, consider combo
Someone has CKD or DKD if they have…..
UACR > 30mg/g
eGFR <60
Can you use ACEi and ARB together?
NO
ARB MOA
Block the activity of angiotensin II at the AT-type 1 receptor
Does ARB have effect on bradykinin metabolism?
nope, so won’t have associated side effect
Stimulation at AT-1 gives you….
Vasoconstriction
Dilation when block
Irbesartan (Avapro) Dose and Frequency
150-300mg, Daily
Lorsartan (Cozaar) Dose and Frequency
50-100mg, 1-2 times daily
Valsartan (Diovan) Dose and Frequency
80-320, Daily
Are ARBs considered 1st line without compelling indication?
Yes
Compelling use of ARBs?
Similar to ACEi
Post-MI, HFrEF, ppl with ASVD risk
Renal protection for patients with protein related DM DKD or CKD
consider losartsn in pts with PMH of gout due to increased urinary uric acid excretion
ARBs efficacy in black patients
less efficacy as mono therapy, consider combo
Contraindications of ARB?
Pregnancy
Bilateral renal artery stenosis
Don’t use ACE with ARBs together
Special use of Losartan
consider in pts with PMH of gout due to increased urinary uric acid excretion
ADE of ACEi and ARBs
Slight SCr rise
Hyperkalemia = most common
Dry Cough*
Angioedema* Rare
*= less common ARBs
What to monitor in ARB?
BP
K
ScCr
BUN
How to deal with ACEi cough
cough meds, etc don’t do shit
Stop taking med
Angioedema info
Not common
2-4 times more frequent in Black people
Due to inhibiting breakdown of bradykinin
Can try an ARB after 6 week washout
ACEi and ARB drug interactions?
K+ sparring diuretics and K+ supplements
Both increase K+ = too high
Direct Renin Inhibitor MOA
Blocks RAAS at its initial point of activation - prevents formation of AT1 and AT2
Aliskiren (Tecturna) Dose and Frequency
150-300mg, daily
Can you use Renin inhibitor with ACE and ARB?
No chance
What to monitor with Direct Renin inhibitor?
Potassium
BUN
SCr
ADE of Direct Renin Inhibitors?
Hyperkalemia Gi upset Cough (Less than ACEi) only 2 cases Angioedema reported high fat meals decrease absorption
Aldosterone Antagonists MOA
Inhibit Aldosterone receptor in distal tubules, increasing NaCL and H20 excretion while conserving K+
Block effect of aldosterone on arteriolar smooth muscle
Spironolactone (Aldactone) Dose and Frequency?
25-100mg, 1-2/day
Avoid Aldosterone Antagonists if….
Anuria
K+ > 5mEq/L, on K+ supp, or K+ diuretic
Acute renal insufficiency (CrCl <30ml/min)
Special Populations for Aldosterone Antagonists?
HF patients with HFrEF
Primary aldosteronism
Resistant HTN
ADEs of Aldosterone Antagonists
Hyperkalemia Hypoatremia Gynecomastia impotence Hypotension