RAAS

Question 1

ACEIs

Answer 1

Lisinopril
Enalapril
Quinapril
Captopril
Ramipril
Benazepril
Fosinopril
Moexipril
Perindopril
Trandolapril

Question 2

ACEIs therapeutic uses

Answer 2

HTN, post-MI
-decrease SV, TPR, systolic/diastolic BP
-Increase compliance of large arteries
-No increase in CO or sympathetic tone
-Minimal postural BP changes
-Possible secondary BP lowering effect from increased bradykinin
L ventricular systolic dysfunction, Systolic HF
-Mild/asymptomatic-severe HF
-Reduced ventricular hypertrophy
-Produces a more hemodynamic state (restore arterial compliance, decrease afterload and wall stress- peripheral vasodilation, long-term venous dilation and preload)

Question 3

ACEI Renal Uses/Effects

Answer 3

CKD: renal protection (DM+non-DM nephropathies)
-decrease capillary pressure (decrease glomerular injury)
-Decreases proteinuria
-Slows progression of renal disease
-Reduction in arteriolar pressure
-Anti-proliferative effects
Quagmire:
-Initial exposure to ACEI/ARB is relatively unexpected by kidney
-Potential initial SCr increase (decline in CrCl) at beginning
-May cause acute kidney injury but resolves overtime

Question 4

ACEIs: ADR’s

Answer 4

• Dry cough (5-20%- reversible upon D/C, can re-challenge, change to ARB)
• Angioedema (may be linked to bradykinin, cannot switch to ARB)
• Hyper-K (consider diet/drug interactions, less aldosterone–>increased K retention)
• Acute renal failure (ARF, increase SCr)
• Teratogenic
• Reduced efficacy in AA

Question 5

ARBs General

Answer 5

• Block receptors for angiotensin II
• No effects on bradykinin: less association to cough, less association to angioedema
• Similar overall net effects, clinical applications, therapeutic uses, and ADRs as ACEI
• HTN, post-MI, HF
• CKD, renal protection –> potential AKI/ARF
• Intolerance to ACEIs (cough)
• Gout

Question 6

ARBs

Answer 6

Losartan
Valsartan
Olmesartan
Irbesartan
Candesartan
Telmisartan
Eprosartan
Azilsartan

Question 7

ARBs: ADR’s

Answer 7

• Lower incidence of cough (wet/dry have been noted)
• Angioedema (potential cross-sensitivity with ACEIs- less likely to develop than ACEIs)
• Hyper-K (aldosterone)
• ARF/AKI (initial SCr bump or CrCl decline)
• Teratogenic
• Reduced efficacy in AA

Question 8

Sacubitril

Answer 8

-Combined with Valsartan (Entresto)
Neprilysin inhibitor:
-enzyme normally degrades vasoactive peptides (natriuretic peptides, bradykinin, adrenomedullin)
-inhibition=more peptides=vasodilation, natriueresis, diuresis, and inhibited pathological growth/fibrosis
-Indicated to reduce risk of CV death and hospitalizations for CHF and reduced EF
-ARNI
-Superior or enalapril
-ADR’s: hyper-K, cough/angioedema, ARF/AKI, hypotension

Question 9

Aliskiren (Tekturna)

Answer 9

• Direct renin inhibitor
• Competitive enzyme inhibitor
• Prevents generation of Angiotensin I (rate limiting step)
• Recently evaluated against enalapril for HF (not superior nor non-inferior)
• ADR’s: hypotension, hyper-K, ARF/AKI, rare angioedema
• Teratogenic
• DO NOT COMBINE with ACEI/ARB: too many ADR’s (hyper-k, etc.), most data not favorable