Mineralcorticoid Receptor Antagonists and Renin Inhibitors

mechanism of action of mineralcorticoid receptor antagonists (MRAs)

antagonism of the MR downregulates expression of:

- epithelial Na channel (ENaC) in the luminal membrane

- Na/K ATPase in the basolateral membrane

- NaCl cotransporter (NCC) in luminal membrane

physiologic effects of MRAs

decreases sodium and water retention leading to decreased BP

steroidal MRAs

- eplerenone

- spironolactone

nonsteroidal MRAs

finerenone

Which steroidal MRA is the least selective?

spironolactone

How long do MRAs take to see antihypertensive effects?

days to weeks after initiation

Which MRAs are metabolized through CYP3A4?

- eplerenone

- finerenone

How are MRAs metabolized and eliminated?

- metabolized through the liver

- eliminated through the kidneys

adverse reactions of MRAs

- acute kidney injury

- gynecomastia

- hyperkalemia

precautions of MRAs

- do not initiate if baseline K >5 mEq/L

- discontinue if K >5.5 mEq/L at any point

- avoid spironolactone/eplerenone if eGFR

key monitoring parameters for MRAs

- BP

- serum potassium

- renal function: SCr, BUN, urine output

- volume status

physiologic effects of renin inhibitors

inhibits renin in the conversion of angiotensinogen to angiotensin I

renin inhibitor

aliskiren (Tekturna)

How long does aliskiren take to have an antihypertensive effect?

within 2 weeks

key points of renin inhibitors

- poorly absorbed, with reduced absorption when taken with high-fat meals

- substrate of P-gp

-eliminated through the kidneys

adverse reactions of renin inhibitors

- acute renal failure

- hyperkalemia

- hypotension

precautions of renin inhibitors

do not use concurrently with an ACE inhibitor or ARB in patients with diabetes

key monitoring parameters for renin inhibitors

- BP

- serum potassium

- renal function: SCr, BUN, urine output

safe use of RAS inhibitors (class purposes)

- do not initiate or increase dose if K >5 mEq/L

- do not initiate or increase dose if SCr increase by >0.3 mg/dL from baseline, documented acute kidney injury, or SCr >2.5 mg/dL