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Flashcards in Potassium-Sparing Deck (16):

Where do K+-sparing diuretics work?

They are otherwise Na+ channel blockers in the cortical collecting ducts or serve as an aldosterone antagonist.


Which diuretics are sodium channel blockers?

Triamterene & Amiloride


Which diuretic is an aldosterone antagonist?



MOA for amiloride?

- Blocks the luminal NA-channel in the collecting duct (ENaC) --> responsible for NA+-K+ exchange --> Sodium is no longer brought into the cell and is secreted, which causes potassium to not be moved into the lumen for excretion.


Effects of amiloride?

- small ↑ Na+ excretion (late in nephron so most has already been reabsorbed)

- blocks major pathway for K+ elimination

- H+, Mg2+, and Ca2+ excretion indirectly decreased


Clinical applications of amiloride?

- Counteracts K+ loss seen in other diuretics used to trx HTN; used to trx HTN and edema, often in combo w/ loop or thiazide diuretic

- Off-label: ascites, peds HTN


PKs of amiloride?

- PO, onset < 2 hrs; directly blocks the channel and has rapid efx when compared to spironolactone

- T1/2: 6-9 hrs, increased w/ ↓ GFR; lasts 12-16 hrs

- Not metabolized, excreted unchanged in urine (>50%) and feces (~40%)

- Drug interactions focus on effx of other K+-sparing drugs (ACEI, ARBs, etc) and exacerbating hypotensive effx of other drugs


Amiloride toxicities?

- Hyperkalemia

- Hyponatremia

- Hypovolemia

- Hyperchloremic metabolic acidosis

- Dizziness, fatigue, HA, NVD, bloating, constipation, leg cramp cramps, blood dyscrasias (rare)


Use of triamterene?

- Similar to amiloride for edema and off-label HTN, rapidly reabsorbed, duration of axn = 6-9 hrs, eliminated as drug metabolites


MOA for spironolactone?

- Competitive antagonist of aldosterone receptors --> ↓ aldosterone-stimulated gene expression (aldosterone hits receptor (NR3C2)--> AIP --> supports either the ENaC on the luminal side or the NA-K ATPase on the interstital side)

- Side effx bc partial agonist at androgen receptor


Effects of spironolactone?

- K+ sparing; blunts ability of aldosterone to promote Na-K exchange in the CDs by ↓ Na+ entry through the luminal channels & ↓ basolateral NA-K ATPase


Clinical applications of spironolactone?

- Counteracts K+ loss seen with other diuretics in the trx of HTN, HF, and ascites

- Trx of primary hyperaldosteronism

- greatly reduces mortality rate in pts w/ severe HF by ↓ myocardial fibrosis, ↓ early morning ↑ in HR, etc

- Off-label: ↓ fibrosis post-MI HF; hirsutism --> trx of androgenic alopecia in females


PKs of spironolactone?

- Has metabolites including canrenone w/ t 1/2 of ~ 20 hrs

- steroid effx are slow on and slow off, so single dose lasts 2-3 days

- drug interactions focus on enhancing effx of other K+-sparing drugs (ACEIs, ARBs, etc) and exacerbating hypotensive effx of other drugs.


Toxicities of spironoloactone?

- hyperkalemia

- amenorrhea, hisutism, gynecomastia, impotence, deepening of voice

- tumorigen in chronic animal tocxcity studies

- Is a sulfa drug, but rare to have HS rxns d/t steroid-binding proteins in plasma and/or its intracellular receptors

- Never give with drugs that ↑ plasma K+, but still used cautiously with ACEI in HF



More selective aldosterone antagonist (also lacks sulfur), approved for use in post-MI HF and alone or in combo for trx of HTN; less gynecomastia, but ~10X more expensive than generic spironolactone


Overall statement regarding K+-sparing diuretics?

- Cause smallest Na+ loss while causing K+ excretion to ↓ below nml.

- Cause significant bicarb loss by interfering with distal H+ secretion