B.10

Question 1

Diuretics

Answer 1

Definition: diuretics increase the urine flow
The clinically relevant diuretics increase the Na+ excretion.
Extrarenal “diuretics”: act outside the nephron, e.g. caffeine, dopamine
Renal diuretics: influence the nephron functions

Question 2

Potassium excreting diuretics

Answer 2

1. Carbonic anhydrase inhibitors: Acetazolamide
2. Loop diuretics: Furosemide, Etacrynic acid
3. Thiazides: Hydrochlorothiazide, Indapamide

Question 3

groups of diuretics

Answer 3

1. Primarily salt excreting diuretics
2. Primarily water excreting diuretics
3. Osmotic diuretics

Question 4

1. Primarily salt excreting diuretics

Answer 4

• carbonic anhydrase inhibitors - proximal tubules
• Loop diuretics- ascending limb of Henle-loop
• Thiazids- distal tubules
• K+ sparing diuretics- upper part of the collecting tubules

Question 5

2. Primarily water excreting diuretics

Answer 5

ADH-antagonists- lower part of the collecting tubules

Question 6

3. Osmotic diuretics

Answer 6

Proximal tubules and the total length of the nephron

Question 7

Acetazolamide

Answer 7

MOA: inhibits Carbonic anhydrase in the proximal tubules
(→no conversion of CO2+H2O to H2CO3→
1. loss of HCO3-,
2. Alkalic urine,
3. metabolic acidosis,
4. ↓plasma bicarbonate cc.→ ↓bicarbonate filtration→↓Na+ excretion→↓diuresis,
5. Increasing proton secretion due to acidosis →acidic urine);
IND: Glaucoma, Adjuvant treatment of edema (CHF, drug SEs, premenstrual edema), Acute mountain disease, Epilepsy (adjuvant), Chronic metabolic alkalosis (caused by loop or thiazide diuretics)
-off lable, Familial periodic paralysis-off lable;
SEs: Hyperchloremic metabolic acidosis, Hypokalemia, Paresthesia, Somnolence, SJS, TEN, Renal stones (cystin & Ca3(PO3)2), BM suppression

Question 8

Hydrochlorothiazide, Indapamide

Answer 8

MOA: (adm. p.o→ excreted by uric acid transporters into the glomeruli lumen→ ↑uric acid in the blood) Inhibit the NaCl reabsorption in the distal convoluted tubules, stimulate the PTH-dependent Ca2+ reabsorption in the distal tubules (due to ↓[Na+]IC the activity of the basolateral Na+/Ca2+ exchanger increases→ increasing the Ca2+ reabsorption);
IND: CHF, HTN, Idiopathic nephrogenic hypercalciuria, Nephrogenic diabetes insipidus;
SEs: Hypokalemia, Metabolic alkalosis, ↓GFR&RBF, ↓glucose tolerance, weakness, fatigue, impotence, Increased risk of basalioma/spinalioma,
(rare SEs- hemolytic anemia, pancreatitis, acute pulmonary edema, cholestatic jaundice, interstitial nephritis)

Question 9

Furosemide

Answer 9

MOA: inhibit the Na+/K+/2Cl- symporter in the ascending limb of Henle-loop
(→1. Na+ and K+ stay inside the loop,
2. ↑water excretion,
3. ↓osmotic gradient,
4. the originally positive lumen potential becomes negative→↑Ca2+ and Mg2+ excretion,
5. ↑PG synthesis (PGs have diuretic and vasodilationg effect),
6. ↑RBF and renin secretion,
7. K+ loss); Structure: sulfonamide structure;
IND: Acute pulmonary edema (LV failure)-vasodilator, congestive HF, HTN (rather for patients with impaired kidney function), Resistant edemas, Acute renal failure, Chronic renal failure, Hypercalcemia, Poisonings (Halogenides, alkalic metals, alkalic earthmetals- except Li);
SEs: Hypokalemia, Transient deafness, Metabolic alkalosis, interstitial nephritis, hematotoxicity;
Contra-IND: Thrombocytopenia

Question 10

Etacrynic acid

Answer 10

MOA: inhibit the Na+/K+/2Cl- symporter in the ascending limb of Henle-loop
(→1. Na+ and K+ stay inside the loop,
2. ↑water excretion,
3. ↓osmotic gradient,
4. the originally positive lumen potential becomes negative→↑Ca2+ and Mg2+ excretion,
5. ↑PG synthesis (PGs have diuretic and vasodilationg effect),
6. ↑RBF and renin secretion,
7. K+ loss);
IND: Acute pulmonary edema (LV failure)-vasodilator, congestive HF, HTN (rather for patients with impaired kidney function), Resistant edemas, Acute renal failure, Chronic renal failure, Hypercalcemia, Poisonings (Halogenides, alkalic metals, alkalic earthmetals- except Li), Gout;
SEs: Hypokalemia, Transient deafness, Metabolic alkalosis

Question 11

Acute mountain disease

Answer 11

altitude sickness, occurs by traveling to high altitudes to quickly

Question 12

Hyperchlomeric metabolic acidosis

Answer 12

results from bicarbonate loss, rather than acid production or retention

Question 13

transepithelial potential

Answer 13

The luminar membrane of the nephron is more hyperpolarized than the basolateral

Question 14

recommended anti-hypertensive combination

Answer 14

Perindopril-Indapamide
ACE-I are often combined with thiazide diuretics

Question 15

contraindicated anti-hypertensive combination

Answer 15

a. Nebivolol-Verapamil (BBL-verapamil)
b. Candesartan-Ramipril (ACE-I - ARBs)
c. Amiloride-Eprosartan (Amiloride with ARBs can lead to toxic hyperkalemia)
e. Sildenafil-Nitroglycerin (Sildenafil-Nitroglycerin)