B.11

Question 1

Potassium sparing diuretics, ADH antagonists, osmotic diuretics

Answer 1

1. Aldosterone antagonists: Spironolactone, Eplerenone
2. Inhibitors of Na+ transporter: Amiloride
3. ADH-antagonists: Tolvaptan
4. Osmotic diuretics: Mannitol, Glycerol

Question 2

antidiuretic

Answer 2

drugs that cause water or salt retention

Question 3

Physiologic antidiuretic

Answer 3

Aldosterone

Question 4

Antidiuretics and their therapeutic IND

Answer 4

Addison’s disease: Fludrocortizone,
cortizone Problems: Na+ and water loss, hyperkalemia (very dangerous→may cause arrhythmias)
Diabetes insipidus: centrallis- Desmopressin (i.v.,s.c.; intranasal BA=3-4%, p.o BA<1%)
Nephrogenic- Thiazide diuretics

Question 5

Spironolactone, Eplerenone

Answer 5

MOA: inhibit the expression of the Aldosteron-dependent Na+/K+ ATPase and the luminar Na+-transporters, they act in the cells of the collecting tubules on aldosterone-Rs (!NOT from the luminar side!), inhibits expression of H+ pumps (→alkaline urine + metabolic acidosis);
Kinetics: act slow, given 1-2X/day, can excrete very resistant edemas (e.g. ascites);
IND: Primary hyperaldosteronism (Conn’s syndrome), Secondary hyperaldosteronism (CHF, liver cirrhosis, Nephrosis), HTN (Eplerenone);
SEs: hyperkalemia, metabolic acidosis, gynecomastia (probably binds to androgen hormone receptors, eplerenone less)

Question 6

Eplerenone

Answer 6

More IND of Eplerenone alone: reduce the risk of CV mortality and morbidity in stable patients with LV dysfunction (LVEF<40%) and clinical evidence of HF after recent MI, to reduce the risk of CV morbidity in adult patients with New York Heart Association (NYHA) class II (chronic) HF and LV systolic dysfunction (LVEF<30%)

Question 7

Amiloride

Answer 7

MOA: inhibits ENaC (→↓Na+ reabsorption in the upper collecting tubules) and, as a consequence, inhibits the K+ excretion (↓Na+ absorption→↓Na+/K+ ATPast activity→↓K+ entry to the cell→↓K+ excretion);
IND: HTN (most commonly combined with thiazides); SEs: hyperkalemia, may cause acidosis

Question 8

Tolvaptan

Answer 8

MOA: ADH-antagonist (in the lower part of the collecting tubules it inhibits the effect of ADH→ no AQ channel→increased water excretion);
IND: AD polycystic kidney disease, SIADH, CHF;
SEs: thirst, polyuria, nocturia, pollakisuria

Question 9

Mannitol, Glycerol

Answer 9

MOA: with their osmotic feature they withdraw water in the nephron→faster flow reduces contact time with the tubular wall→more Na+ is excreted as well;
Kinetics: given P.E, very strong diuretics;
IND: Acute renal failure, cerebral edema;
SEs: can worsen edematous states (e.g. Pulmonary edema), Hyponatremia, Dehydration (→if water replacement isn’t adequate)

Question 10

SIADH

Answer 10

syndrome of inappropriate antidiuretic hormone secretion

Question 11

Pollakisuria

Answer 11

increased frequency of urination;