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
- 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?
- 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