Renal

Question 1

What drugs act on the proximal tubule?

Answer 1

Mannitol and Acetazolamide. Mannitol also works on the descending loop of Henle and the collecting duct.

Question 2

What drugs act on the thick ascending limb of the loop of Henle?

Answer 2

Loop diuretics (Furosemide and Ethacrynic acid)

Question 3

What drugs act on the distal convoluted tubule?

Answer 3

Thiazides (Hydrochlorothiazide)

Question 4

What drugs act on the cortical collecting duct?

Answer 4

K+ sparing diuretics

Question 5

What drugs act on the collecting tubule?

Answer 5

ADH antagonists

Question 6

What is the mechanism of Mannitol?

Answer 6

Osmotic diuretic, ↑ tubular fluid osmolarity, producing ↑ urine flow, ↓ intracranial/intraocular pressure.

Question 7

What is the clinical use of Mannitol?

Answer 7

Drug overdose, ↑ intracranial/intraocular pressure.

Question 8

What is the toxicity of Mannitol?

Answer 8

Pulmonary edema, dehydration. Contraindicated in anuria, CHF.

Question 9

What is the mechanism of Acetazolamide?

Answer 9

Carbonic anhydrase inhibitor. Causes self-limited NaHCO3 diuresis and ↓ total-body HCO3− stores.

Question 10

What is the clinical use of Acetazolamide?

Answer 10

Glaucoma, urinary alkalinization, metabolic alkalosis, altitude sickness, pseudotumor cerebri.

Question 11

What is the toxicity of Acetazolamide?

Answer 11

Hyperchloremic metabolic acidosis, paresthesias, NH3 toxicity, sulfa allergy.

Question 12

Loop diuretics - What is the mechanism of Furosemide?

Answer 12

Sulfonamide loop diuretic. Inhibits cotransport system (Na+/K+/2 Cl−) of thick ascending limb of loop of Henle. Abolishes hypertonicity of medulla, preventing concentration of urine.
Stimulates PGE release (vasodilatory effect
on afferent arteriole); inhibited by NSAIDs.
↑ Ca2+ excretion. Loops Lose calcium.

Question 13

Loop diuretics - What is the clinical use ofFurosemide?

Answer 13

Edematous states (CHF, cirrhosis, nephrotic syndrome, pulmonary edema), hypertension, hypercalcemia.

Question 14

Loop diuretics - What is the toxicity of Furosemide?

Answer 14

OH DANG! - Ototoxicity, Hypokalemia, Dehydration, Allergy (sulfa), Nephritis (interstitial), Gout.

Question 15

Loop diuretics - What is the mechanism of Ethacrynic acid?

Answer 15

Phenoxyacetic acid derivative (not a sulfonamide). Essentially same action as furosemide.

Question 16

Loop diuretics - What is the clinical use of Ethacrynic acid?

Answer 16

Diuresis in patients allergic to sulfa drugs.

Question 17

Loop diuretics - What is the toxicity of Ethacrynic acid?

Answer 17

Similar to furosemide; can cause hyperuricemia; never use to treat gout.

Question 18

What is the mechanism of Hydrochlorothiazide?

Answer 18

Thiazide diuretic. Inhibits NaCl reabsorption in early distal tubule, ↓ diluting capacity of the nephron. ↓ Ca2+ excretion.

Question 19

What is the clinical use of Hydrochlorothiazide?

Answer 19

Hypertension, CHF, idiopathic hypercalciuria, nephrogenic diabetes insipidus, osteoporosis.

Question 20

What is the toxicity of Hydrochlorothiazide?

Answer 20

Hypokalemic metabolic alkalosis, hyponatremia, hyperglycemia, hyperlipidemia, hyperuricemia, and hypercalcemia. Sulfa allergy.

Question 21

What are the K+ sparing diuretics?

Answer 21

Spironolactone and eplerenone; Triamterene, and Amiloride.

Question 22

What is the mechanism of K+ sparing diuretics?

Answer 22

Spironolactone and eplerenone are competitive aldosterone receptor antagonists in the cortical collecting tubule. Triamterene and amiloride act at the same part of the tubule by blocking Na+ channels in the CCT.

Question 23

What is the clinical use of K+ sparing diuretics?

Answer 23

Hyperaldosteronism, K+ depletion, CHF

Question 24

What is the toxicity of K+ sparing diuretics?

Answer 24

Hyperkalemia (can lead to arrhythmias), endocrine effects with spironolactone (e.g., gynecomastia, antiandrogen effects).

Question 25

What effect do diuretics have on Urine NaCl?

Answer 25

↑ (all diuretics except acetazolamide). Serum NaCl may ↓ as a result.

Question 26

What effect do diuretics have on Urine K+?

Answer 26

↑ with loop and thiazide diuretics. Serum K+ may ↓ as a result.

Question 27

Describe how diuretics can cause acidemia.

Answer 27

↓ (acidemia): carbonic anhydrase inhibitors— ↓ HCO3− reabsorption. K+ sparing—aldosterone blockade prevents K+ secretion and H+ secretion. Additionally, hyperkalemia leads to K+ entering all cells (via H+/K+ exchanger) in exchange for H+ exiting cells.

Question 28

Describe how diuretics can cause alkalemia.

Answer 28

↑ (alkalemia): loop diuretics and thiazides cause alkalemia through several mechanisms: ▪ Volume contraction → ↑ AT II → ↑ Na+/H+ exchange in proximal tubule → ↑ HCO3− reabsorption (“contraction alkalosis”) ▪ K+ loss leads to K+ exiting all cells (via H+/K+ exchanger) in exchange for H+ entering cells ▪ In low K+ state, H+ (rather than K+) is exchanged for Na+ in cortical collecting tubule, → alkalosis and “paradoxical aciduria”

Question 29

What effect do diuretics have on Urine Ca2+?

Answer 29

↑ with loop diuretics: ↓ paracellular Ca2+ reabsorption → hypocalcemia ↓ with thiazides: Enhanced paracellular Ca2+ reabsorption in distal tubule

Question 30

What are the ACE inhibitors?

Answer 30

Captopril, enalapril, lisinopril

Question 31

What is the mechanism of ACE inhibitors?

Answer 31

Inhibit ACE → ↓ angiotensin II → ↓ GFR by preventing constriction of efferent arterioles. Levels of renin ↑ as a result of loss of feedback inhibition. Inhibition of ACE also prevents inactivation of bradykinin, a potent vasodilator. Angiotensin II receptor blockers (-sartans) have effects similar to ACE inhibitors but do not ↑ bradykinin → ↓ risk of cough or angioedema.

Question 32

What is the clinical use of ACE inhibitors?

Answer 32

Hypertension, CHF, proteinuria, diabetic nephropathy. Prevent unfavorable heart remodeling as a result of chronic hypertension

Question 33

What are the toxicities of ACE inhibitors?

Answer 33

Cough, Angioedema (contraindicated in C1 esterase inhibitor deficiency), Teratogen (fetal renal malformations), ↑ Creatinine (↓ GFR), Hyperkalemia, and Hypotension. Avoid in bilateral renal artery stenosis, because ACE inhibitors will further ↓ GFR → renal failure.

Question 34

Prostaglandins dilate the afferent arteriole (↑ RPF, ↑ GFR, so FF remains constant). What drug inhibits this?

Answer 34

NSAIDs; use may result in acute renal failure

Question 35

Angiotensin II preferentially constricts efferent arteriole (↓ RPF, ↑ GFR, so FF increases). What drug inhibits this?

Answer 35

ACE inhibitor

Question 36

What is Hartnup disease treated with?

Answer 36

High-protein diet and nicotinic acid

Question 37

What is Liddle syndrome treated with?

Answer 37

Amiloride

Question 38

What drugs shift K+ out of cell (causing hyperkalemia)

Answer 38

Digitalis and β-adrenergic antagonist

Question 39

What drugs shift K+ into cell (causing hypokalemia)?

Answer 39

β-adrenergic agonist (↑ Na+/K+ ATPase)

Question 40

What drugs cause Type 1 Renal tubular acidosis (distal, pH >5.5)?

Answer 40

Amphotericin B toxicity. Analgesic nephropathy is also a cause.

Question 41

What drugs cause Type 2 Renal tubular acidosis (proximal, pH <5.5)?

Answer 41

Carbonic anydrase inhibitors

Question 42

What drugs cause Type 3 Renal tubular acidosis (hyperkalemic, pH <5.5)?

Answer 42

K+ sparing diuretics

Question 43

What drugs cause Membranous nephropathy?

Answer 43

NSAIDs, pencillamine

Question 44

What drug is used to treat Minimal change disease (lipoid nephrosis)?

Answer 44

Excellent response to corticosteroids

Question 45

What drugs are treatments for recurrent kidney stones (Calcium)?

Answer 45

Thiazides and citrate

Question 46

What drugs cause Drug-induced interstitial nephritis (tubulointerstitial nephritis)?

Answer 46

Certain drugs (e.g., diuretics, penicillin derivatives, sulfonamides, rifampin)

Question 47

What drug causes Renal papillary necrosis?

Answer 47

Chronic phenacetin use (acetaminophen is phenacetin derivative)