Potassium-Sparing

Question 1

Where do K+-sparing diuretics work?

Answer 1

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

Question 2

Which diuretics are sodium channel blockers?

Answer 2

Triamterene & Amiloride

Question 3

Which diuretic is an aldosterone antagonist?

Answer 3

Spironolactone

Question 4

MOA for amiloride?

Answer 4

• 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.

Question 5

Effects of amiloride?

Answer 5

• 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

Question 6

Clinical applications of amiloride?

Answer 6

• 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

Question 7

PKs of amiloride?

Answer 7

• 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

Question 8

Amiloride toxicities?

Answer 8

• Hyperkalemia
• Hyponatremia
• Hypovolemia
• Hyperchloremic metabolic acidosis
• Dizziness, fatigue, HA, NVD, bloating, constipation, leg cramp cramps, blood dyscrasias (rare)

Question 9

Use of triamterene?

Answer 9

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

Question 10

MOA for spironolactone?

Answer 10

• 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

Question 11

Effects of spironolactone?

Answer 11

• 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

Question 12

Clinical applications of spironolactone?

Answer 12

• 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

Question 13

PKs of spironolactone?

Answer 13

• 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.

Question 14

Toxicities of spironoloactone?

Answer 14

• 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

Question 15

Eplerenone?

Answer 15

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

Question 16

Overall statement regarding K+-sparing diuretics?

Answer 16

• Cause smallest Na+ loss while causing K+ excretion to ↓ below nml.
• Cause significant bicarb loss by interfering with distal H+ secretion