K-sparring (amboss and UW)

Question 1

K-sparring agents?

Answer 1

Aldosterone receptor antagonists: spironolactone, eplerenone

Epithelial sodium channel blockers: triamterene, amiloride

Question 2

Aldosterone receptor antagonists?

Answer 2

Aldosterone receptor antagonists: spironolactone, eplerenone

Question 3

Epithelial sodium channel blockers?

Answer 3

Triamterene, amiloride

Question 4

Mechanism of aldosterone rec antag?

Answer 4

Competitively bind to aldosterone receptors in the late distal convoluted tubule and the collecting duct → inhibition of the effects of aldosterone → decreased Na+ reabsorption and K+ excretion → diuresis

Question 5

H+ in aldosterone antag?

Answer 5

Decreased H+ excretion → acidosis

Question 6

Evolving hyperkalemia induces H+/K+-ATPases in all cells to counteract the increase in serum K+ → K+ enters cells in exchange for H+ → amplifies acidosis.

Answer 6

.

Question 7

Which one does not cause endocrine side effect?

Answer 7

Eplerenone is more receptor-specific than spironolactone and, therefore, does not cause endocrine side effects.

Question 8

Spironolactone also acts (nonspecifically) on sex hormone receptors → endocrine side effects

Answer 8

.

Question 9

Epithelial sodium channel blockers (triamterene, amiloride) mechanism?

Answer 9

direct inhibition of the epithelial sodium channels (ENaC) in the distal convoluted tubule and the collecting duct → reduced Na+ reabsorption and reduced K+ secretion → diuresis

Question 10

Where are aldosterone receptors?

Answer 10

Specifically in the distal convoluted tubule of the late distal tubule

Question 11

Aldosterone is a mineralocorticoid hormone that promotes synthesis and incorporation of Na+ channels and Na+/K+-ATPases into the tubule and duct walls. This process normally leads to increased reabsorption of sodium and increased excretion of potassium. Blocking of channel synthesis and incorporation is a genomic effect that requires several hours. Therefore, aldosterone receptor antagonists are not effective until 24–48 hours following administration.

Answer 11

.

Question 12

When aldosterone receptor antagonists become effective/ time

Answer 12

Aldosterone receptor antagonists are not effective until 24–48 hours following administration.

Question 13

Indications?

Answer 13

Hypertension (especially if hypokalemia is also present)

Ascites/edema due to congestive heart failure, nephrotic syndrome, or cirrhosis of the liver (mainly spironolactone)

Hyperaldosteronism (Conn syndrome)

Nephrogenic diabetes insipidus (amiloride)

Hypokalemia (K depletion)

Hyperandrogenic states, e.g., polycystic ovary syndrome (spironolactone) - antiandrogen

Question 14

Why in ascites/edema due to congestive HF, nephrotic syndrome, or cirrhosis of the liver is mainly used spironolactone?

Answer 14

Triamterene and amiloride are often combined with thiazide diuretics to maintain stable serum potassium levels.

Question 15

Treatment of hyperaldosteronism (conn syndrome)?

Answer 15

only spironolactone

Question 16

Nephrogenic diabetes insipidus treatment?

Answer 16

amiloride

Question 17

Hyperandrogenic states, e.g., polycystic ovary syndrome, treatment?

Answer 17

spironolactone

Question 18

Side effects. General?

Answer 18

General side effects:

Metabolic and electrolyte imbalances, such as hyperkalemia!!! (can lead to arrythmia), hyponatremia, and metabolic acidosis, can lead to cardiac arrhythmias

Gastrointestinal disturbances (nausea, vomiting, diarrhea)

Question 19

Side effects. Spironolactone-specific side effects?

Answer 19

Spironolactone-specific side effects: ENDOCRINE disturbances

Men: antiandrogenic effects (e.g., gynecomastia!!!, erectile dysfunction)

Women: amenorrhea

Question 20

General contraindications?

Answer 20

Anuria and/or renal insufficiency

Preexisting hyperkalemia

Addison disease

Combination with other potassium-sparing diuretics or potassium supplements

Question 21

Specific contraindications? Spironolactone

Answer 21

Use with caution in patients with CHF with either of the following:

a) GFR < 30 mL/min
b) Creatinine ≥ 2.5 mg/dL (men) or ≥ 2 mg/dL (women)

Question 22

Specific contraindications? Eplerenone

Answer 22

Concomitant use of strong CYP3A4 inhibitors

Patients with hypertension with concomitant type II diabetes mellitus and microalbuminuria or with renal insufficiency (serum creatinine > 2.0 mg/dL for men or > 1.8 mg/dL for women; or creatinine clearance < 50 mL/min)

Creatinine clearance < 30 mL/min

Question 23

What enzyme metabolizes eplerenone?

Answer 23

CYP3A4 (INTERACTIONS!!!)

Question 24

Specific contraindications? Amiloride

Answer 24

diabetic nephropathy

Question 25

What medications used in synergy with loop and thiazide? why

Answer 25

all thiazides to limit potassium loss

Question 26

What degree of natriuresis due to amiloride and spironolactone?

Answer 26

mild degree

Question 27

Why potassium sparing casue hyperkalemia and metabolic acidosis?

Answer 27

decr reab of Na in collecting tubule –> reduced luminal electronegative gradient, which is a major driving force for K and H secretion by principal and intercalated cells, respectively.

Question 28

What electrolyte and what cell? principal cells

Answer 28

K

Question 29

What electrolyte and what cell? intercalated cells

Answer 29

H

Question 30

All cause hyperkalemia

Answer 30

.

Question 31

Where happens final adjustments to electrolytes and water content?

Answer 31

collecting duct system

Question 32

K sparring. total body electrolytes? Na

Answer 32

decr (1 arrow down)

Question 33

K sparring. total body electrolytes? K

Answer 33

incr (1 arrow up)

Question 34

K sparring. total body electrolytes? HCO3

Answer 34

decr (1 arrow down)

Question 35

K sparring. total body electrolytes? Ca

Answer 35

no change

Question 36

K sparring. total body electrolytes? Uremic acid

Answer 36

no change

Question 37

how spironolactone and eprelenone acts on receptors?

Answer 37

competitive antagonists in cortical collecting tubules