RAAS drugs Flashcards
RAAS fxn
increase blood volume and blood pressure when it is low
what does blocking RAAS do?
reduce blood volume and pressure
RAAS regulates
Blood pressure
Blood volume
Fluid and Electrolyte balance
- also mediates changes associated with hypertension, heart failure and MI
Where does RAAS exerts its effect through
angiotensin II and aldosterone
aldosterone
increases Na+ reabsorption form the nrpgron tubule
angiotensin II
increased release of vasopressin
= increased H2) reabsorption from kidneys
= increased blood volume and blood pressure
actions of angiotensin II
vasoconstriction
- stimulates posterior pituitary to release vasopressin
- a) vasoconstriction
-b) increased H2) reabsorption from nephron
Stimulate aldosterone
- acts on adrenal cortex –> secrete aldosterone
- enhances Na+ reabsorption from nephron
Both raise BP
Actions of Aldosterone
acts on distal nephron tubule
- increase Na+ reabsorption
–> h20 follows na
- increases BP/volume
Renin
converts angiotensinogen into angiotensinogen I
Angiotensin - Converting Enzyme (ACE)
converts angiotensin I into active state angiotensin II.
2 process of BP regulation by RAAS
1) Vasoconstriction- occurs within MINUTES
2) Renal retention of sodium - DAYS/ WEEKS
what are 2 ways angiotensin II promotes water retention
1) reducing glomerular filtration
- reduce urinary output (via vasoconstriction)
2) Aldosterone
- increase Na+ reabsorption and water follows na+
ACE inhibitor drug name
Catopril
ACE inhibitor fxn
prodrug treating hypertension, heart failure, and MI
Mechanism of ACE inhibitors
reduce angio II levels by inhibiting ACE
- decrease BV
Increase levels of Bradykinin
- natural body vasodilator
Pharmakinetics of ACE inhibitors
A) PO with food
M) Prolonged half-life, administration 2x / day
Excretion: KIDNEYS = dangerous levels = kidney disease
therapeutic use of ACE inhibitors
reduction of hypertension
Heart failure
- prevent/ reverse pathologic changes in cardiac structure
Prevention of MI and Stroke
- reduction BP/BV
Diabetic Nephropathy: leading cause of end stage renal disease
– slow progression of disease by lowering systemin BP= reducing glomerular filter pressure
ACE inhibitor Adverse Effects
First Dose hypotension (wide-spread vasodilation
Hyperkalemia
Increased bradykinin
- cough
- angioedema: swelling like hives but underneath skin
Contradiction Renal failure in patients with renal artery stenosis (RAS)
- pt require greater pressure to overcome RAS
–> kidney secretes large amounts of renin
- ACE inhibitors stop this adaptation
- Contraindication for pt with RAS
ACE inhibitor drug interactions
Diuretics
- may intensify first dose hypotension
Antihypertensive drugs
- may need to be reduced
NSAIDs
- reduce antihypertensive effects of ACE inhibitors
Preparation and administration of anti ACE inhibitors
PO
available in combo with hydrochlorothiazide and perindopril
some combined with calcium channel blockers
Angiotensin II Receptor Blocker drug name
Losartan
ANG II receptor blockers work by
blocking action of ANG II
Difference between ANG II receptor blockers and ACE inhib.
ace inhib- block production of ANG II
ang II recept. blockers = block action of ANG II
- less risk of cough and hyperkalemia
ACE inhib. preferred
Direct Renin Inhibitors (DRI)
Aliskiren
DRI mechanism
binds tightly with renin
-inhibits cleavage of ANG into ANG I
reduces influence of entire RAAS
- reduced BV/BP
Therapeutic uses of DRI
Hypertension
- reduces BP to same level as ACE inhib
Pharmacokinetics of DRI
OP with high fat meal
Half-life = 24 hours
DRI adverse effects
Well tolerated
GI: dose dependent diarrhea, abd. pain, dyspepsia
Hyperkalemia if used with ACE inhib.
dyspepsia
indigestion, upset stomach
Prep, dosage, admin of DRI
Alone: 150 mg/day
- may increase to 300 mg
- above this diarrhea increased significantly
Aldosterone Antagonist
Eplerenone
- first line
Mech of Aldosterone Antagonist
Blocks aldosterone receptors
- decreased Na+ reabsorption
= water stays in kidney
= reduced BP/BV
Therapeutic uses of Aldosterone Antagonist
Hypertension
- max reduction takes 4 weeks
- combination with ACE inhib or ARB produces further redicution in BP
Heart Failure
Aldosterone Antagonist Pharmacokinetic
OP- not affected by food
Adverse effects of Aldosterone Antagonist
Hyperkalemia (occurs secondary to sodium retention)
- don’t combine with sodium potassium supplements
- contraindication for patients with high serum potassium (above 5.5 mEq/L)
Aldosterone Antagonist drug interactions
P450 inhibitors
- increased levels eplerenone = toxicity
Drugs that raise potassium blood levels
