ACEs And ARBs

Question 1

Renin release effects:

Answer 1

Renin release -> Increase BP

Decrease pre-glomerilar BP -> renin release
Decrease NaCl reabsorption -> renin release
Activation of Beta 1 receptors on juxtglomerular cells -> renin release

Question 2

Angiotensin II receptor location: Kidney

Answer 2

Effects of activation:

Intrarenal vasoconstriction -> Increase BP, decrease GFR

Increase Na/H2O reabsorption in renal tubules -> Na/H2O retention -> K excretion

Question 3

Angiotensin II receptor location: Adrenal Gland

Answer 3

Cortex -> increase aldosterone -> increase total peripheral resistance

Medulla -> increase NE/E release

Question 4

Angiotensin II receptor location: Vascular Smooth Muscle

Answer 4

Vasoconstriction -> increase total peripheral resistance

Growth promoting factors for blood vessels, thickening, atherogenic

Question 5

Angiotensin II receptor location: CNS

Answer 5

Increase adrenal drive -> increase TPR, increase CO

Increase ADH -> increase H2O reabsorption

Increase thirst -> increase H2O ingestion

Question 6

Principle effects/uses of ACEis or ARBs

Answer 6

Reduce total peripheral resistance (TPO) and BP

Diminish proteinuria and stabilize renal function - diabetes/CKD benefit “renal protection”

Mortality benefit in HR post MI

Minimal effecrs on HR and CO - no reflex sympathetic activation - suppressing sympathetic response while vasodilation, safe in ischemic heart disease

Question 7

ACEis - drugs, MOA, Net effect

Answer 7

-prils (Lisinopril, enalapril, quinapril)

MOA: inhibit angiotensin-converting enzyme (ACE)

Effector organs:
Kidneys - stabolization of renal function
Adrenal gland - decreased aldosterone secretion
Vascular SM - vasodilation
CNS - decrease sympathetic activity

Question 8

ACEis ADRs and uses

Answer 8

Uses:

Cardiac uses: HTN - secondary lowering effect from increase bradykinin, post MI, HRrEF
Renal uses: chronic kidney disease, decrease proteinuria - improve renal blood flow

Potential decline in CrCl at beginning of dosing with ACE/ARB in renal failure - start slow dosing, labs in 1 week

ADRS: AKI/ARF
Dry cough- ACE -> ARB
Angioedema - less risk with ARBs, switch after 6 weeks
Hyperkalemia (K) - less aldosterone -> increase K retention
Teteragoenic

Reduced efficacy in AA - renin is not a player in HTN of AAs so drug is less effective, potentially appropriate for CKD

Question 9

ARBS drugs, MOA, net effect

Answer 9

-sartans (Losartan, valsartan, ole spartan)

MOA: blocks angiotensin II receptors

Net effect:
Kidney - stabilize kidney function, nephroprotective
Adrenal gland - decrease aldosterone secretion
Vascular SM - vasodilation
CNS - decrease sympathetic activity

Question 10

ARBs uses and ADRs

Answer 10

Uses: HTN, post MI, HF

ADRs: 
AKI/ARF - initial SCr bump and CrCl decline
Hyperkalemia - aldosterone 
Teratogenic 
Reduced efficacy in AA

Question 11

Neprilysin inhibitor

Answer 11

Angiotensin receptor-neprolysin inhibitor = “ARNI”

Drug examples: Entresto ( sacubitril + valsartan)

MOA: more beneficial vasoactive peptides

Net effect: vasodilation, lower BO, decrease sympathetic tone, decrease aldosterone, natruriesis, diuresis

Uses: HFrEF
Reduce risk of death and hospitalizations

ACE, ARB or ARNI

ADRs: 
Hyperkalemia (K)
Cough/angioedema
AKI/ARF
Hypotension

Question 12

Direct renin inhibitor

Answer 12

Aliskiren (tekturna)

MOA: competitive enzyme - prevents generation of angiotensin I

Not a good drug - comparable BP reduction to ACE/ARB in HTN

Net effect: decrease BP, no generation of angiotensin I

ADRs:
Hypotension
Hyperkalemia (K)
ARK/AKI
Rare angioedema 

DO NOT combine with ACEI or ARB - lethal side effects: increased hypotension dry cough, angioedema