Lec 10 Heart Failure Pharm Flashcards
What is path of RAAS system?
- angiotensin from liver
- converted to angiotensin I by renin from kidney
- converted to angiotensin II by ACE from lungs
- angiotensin II acts of angiotensin receptors AT1-4
What is action of RAAS system if hypotension?
- kidneys sense decrease blood flow –> release renin –> get angiotensin II which causes:
- -> systemic vasoconstriction –> higher BP
- -> increase sympathetic
- -> aldosterone release from adrenal –> Na and fluid retention
- -> ADH release from posterior pituitary –> fluid retention
- -> increase thirst –> increase blood volume
What are the downstream effects of angiotensin II?
changes in peripheral resistance by: direct vasoconstriction, increase sympathetic, ADH and aldosterone release
changes in renal function: increase Na reabsorption, increase renal sympathetic tone
structural changes: increase growth factors, increase afterload increase wall tension leading to vascular and cardiac hypertrophy and remodeling
What is prorenin?
- secreted from kidney and extrarenal tissue
- can be converted to renin in JG cells of kidney
- binds the same receptor as renin and activates transcription factors associated with fibrosis
Where is renin released from?
JG cells in kidney
What is action of renin?
- converts angiotensinogen to angiotensin I
- binds pro-renin receptor to activate fibrosis
How is renin regulated?
- Na delivery to macula densa: less NaCl to macula densa = more renin release
- intrarenal baroreceptor: less renal perfusion pressure = more renin release
- B-adrenergic receptor: B1 cell on juxtaglomerular cells; activated by hypotension and as part of sympathetic activationa and cause more renin release
What is feedback loop on renin?
Angiotensin II inhibits JG cells from releasing renin
What is action of aldosterone?
- reabsorption Na/Cl and H2O
- excretion of K
What is equation for GFR?
GFR = Kf * Net filtration pressure
Kf = filtration coefficietn
What is equation for net filtration pressure?
(Pgc - πgc) - (Pbc - πbs)
P = hydrostatic π = oncotic; πbc = 0 normally
What happens to afferent/efferent arterioles in kidney with angiotensin II? To Pgc/GFR?
both constricted by efferent constricted more –> high Pgc –> high GFR
What happens to afferent/efferent arterioles in kidney with renin inhibitor [aliskiren]? To Pgc/GFR? Albumin? Creatinine?
- efferent dilated more than afferent
- -> decreasd kidney flow –> decrease Pgc –> decrease GFR
- less glomerular pressure, less albumin/ creatinine excretion
What is mech of action ACE inhibitor? What processes does it inhibit?
- competitively inhibits ACE
inhibits: - conversion AT1 to AT2 [so less AT II]
- bradykinin inactivation [so more bradykinin]
- Ac-SDKP stem cell regulator [so more of it]
What happens to afferent/efferent arterioles in kidney with ACE inhibitor [lisonopril]? To Pgc/GFR? Albumin? Creatinine?
- efferent dilated more than afferent
- -> decreasd kidney flow –> decrease Pgc –> decrease GFR
- less glomerular pressure, less albumin/ creatinine excretion
What are the 3 ACE inhibitors we should know?
- captopril
- enalapril
- lisonopril
What is a unique side effect of captopril?
changes in taste
What are ARBs?
angiotensin II reeptor antagonists
selective for AT1 receptor over AT2
With beta blockers what happens to:
- renin activity
- renin concentration
- angiotensinogen
- AT I
- ATII
- low renin activity
- low renin concentration
- no change in angiotensinogen/AT I/ATII
With renin inhibitors what happens to:
- renin activity
- renin concentration
- angiotensinogen
- AT I
- ATII
- low renin activity = direct inhibition from drug
- high renin conc = feedback from ATII
- low ATI/ATII conc
- no change in angiotensinogen
With ACE inhibitors what happens to:
- renin activity
- renin concentration
- angiotensinogen
- AT I
- ATII
- high renin activity/conc = feedback from low AT II
- low angiotensinogen
- high AT I
- low AT II = directly inhibited by ACEI
With ARBs what happens to:
- renin activity
- renin concentration
- angiotensinogen
- AT I
- ATII
- high renin activity/conc = feedback from low AT II activity
- low angiotensinogen
- high AT I
- high AT II conc = but not active since directly blocked by ARB
What is action of bradykinin?
acts on B1 receptors: vasoconstriction
acts on B2 receptors: vasodilation, NO + prostaglandin production –> inflammation
What is ANP?
atrial natruiertic peptide
- released from atrial myocytes in CHF when atrial stretch with increase volume to cause kidney to get rid of Na/H2O
