Renal drugs

Question 1

mannitol - mechanism, clinical use and toxicity

Answer 1

mechanism: osmotic diuretic; increase tubular fluid osmolarity -> increase urine flow, decrease intracranial/ocular pressure
use: drug OD, elevated intracranial/ocular pressure

Toxicity: pulmonary edema, dehydration. Contraindicated in anuria, HF

Question 2

Acetazolamide - mechanism, clinical use and toxicity

Answer 2

Mechanism: carbonic anhydrase inhibitor. Causes self-limited NaHCO3 excretion and decreases total body bicarb stores

Use: Glaucoma, urinary alkalinization, metabolic alkalosis, altitude sickness, pseudotumor cerebri

Toxicity: hyperchloremic metabolic acidosis, paresthesias, ammonia toxicity, sulfa allergy

Question 3

Furosemide, bumetanide, torsemide - mechanism and use

Answer 3

Sulfonamide loop diuretics
Mechanism:
-inhibit Na/K/2Cl cotransporter of thick ascending limb –> decreases hypertonicity of medulla preventing concentration of urine

• stimulates PGE release (vasodilates afferent arteriole)
• inhibited by NSAIDs
• increase Ca2+ excretion

Use: edematous states, HT, hypercalcemia

Question 4

Furosemide, bumetanide, torsemide - toxicity

Answer 4

ototoxicity, hypokalemia, dehydration, allergy (sulfa), nephritis (interstitial), gout

Question 5

Ethacrynic acid

Answer 5

Phenoxyacetic acid derivative (NOT a sulfonamide)

Inhibits Na/K/2Cl transporter -> prevents concentration of urine, increased calcium excretion, stimulates PGE release which dilates afferent arteriole

Use: diuresis in patients with sulfa allergy

Toxicity: can cause hyperuricemia (do not use to treat gout)

Question 6

Thiazide diuretics- mechanism, clinical use and toxicity

Answer 6

HCTZ, chlorthalidone

Mechanism: inhibit NaCl reabsorption in early DCT -> decreased diluting capacity of nephron. Decreases calcium excretion -> hypercalcemia

Clinical use: HTN, HF, idiopathic hypercalciuria, nephrogenic diabetes insipidus, osteoporosis

Toxicity: (HyperGLUC)
Hypokalemic metabolic acidosis
Hyponatremia 
HyperGlycemia
HyperLipidemia
HyperUricemia
HyperCalcemia
Sulfa allergy

Question 7

Spironolactone and eplerenone- mechanism, clinical use and toxicity

Answer 7

K+ sparing diuretics

Mechanism: competitive aldosterone receptor antagonists in collecting tubule

Clinical use: Hyperaldosteronism, K+ depletion, HF

Toxicity: hyperkalemia (can lead to arrhythmias), spironolactone can have endocrine effects such as *gynecomastia and antiandrogen effects

Question 8

Triamterene and amiloride - mechanism, clinical use and toxicity

Answer 8

K+ sparing diuretics

Mechanism: block Na+ channels in collecting tubule

Clinical use: Hyperaldosteronism, K+ depletion, HF

Toxicity: hyperkalemia (can lead to arrhythmias)

Question 9

ACE inhibitors - mechanism, clinical use

Answer 9

Captopril, lisinopril, enalapril, ramipril

Mechanism: inhibit ACE -> decreased ATII -> decreased GFR; Renin increases due to loss of negative feedback.
ACE inhibition prevents inactivation of bradykinin, potent vasodilator

Clinical use: HTN, HF, proteinuria, diabetic nephropathy (decreases intraglomerular P -> slows GBM thickening), prevents unfavorable heart remodeling as result of chronic HTN

Question 10

Which diuretics increase urine NaCl?

Answer 10

All except acetazolamide, Serum NaCl may decrease as result

Question 11

Which diuretics increase urine K+?

Answer 11

loop and thiazide diuretics

serum K+ may decrease as result

Question 12

Which diuretics increase blood pH (alkylosis)?

Answer 12

loop diuretics and thiazides can cause alkalemia by:

• volume contraction -> increased ATII -> Na+/H+ exchange in PCT -> increased bicarb reabsorption “Contraction alkylosis”
• K+ loss leads to K+ exiting cells via H+/K+ exchanger for H+ entering cells
• in low K+ state, H+ is exchanged for Na+ in cortical collecting tubule instead of K+ -> alkalosis and “paradoxical aciduria”

Question 13

which diuretics decrease blood pH (acidosis)?

Answer 13

carbonic anhydrase inhibitors: decrease bicarb reabsorption

K+ sparing: aldosterone blocking prevents K+ and H+ secretion. Hyperkalemia leads to K+ entering all cells (H+/K+ exhchanger) and H+ exits cells

Question 14

Which diuretics increase urine calcium?

Answer 14

loop diuretics: decreased paracellular calcium reabsorption -> hypocalcemia

Question 15

Which diuretics decrease urine calcium

Answer 15

thiazides: enhanced calcium reabsorption in DCT

Question 16

Angiotensin II receptor blockers (ARBs)- mechanism, clinical use and toxicity

Answer 16

losartan, candesartan, valsartan

Mechanism: selectively blocks binding of AT II to AT1 receptor. Effects similar to ACE without increasing bradykinin

Clinical use: HTN, HF, proteinuria, or diabetic nephropathy with intolerance to ACE inhibitors (cough, angioedema)

Toxicity: hyperkalemia, decreased renal function, hypotension, teratogen

Question 17

Aliskiren - mechanism, clinical use and toxicity

Answer 17

Mechanism: Direct renin inhibitor, blocks conversion of AT to AT I

Clinical use: HTN

Toxicity: Hyperkalemia, decreased renal function, hypotension

**Contraindicated in diabetics taking ACE inhibitors or ARBs

Question 18

ACE inhibitor toxicity

Answer 18

Toxicity: 
Cough
Angioedema (contraindicated in C1 esterase inhibitor deficiency)
Teratogen (fetal renal malformations)
increases Creatinine (decreased GFR)
Hyperkalemia
Hypotension

Avoid in bilateral renal artery stenosis b/c further decrease in GFR will cause renal failure