Fa: Renal - Pharmacology

Front 1

Which drug is an osmotic diuretic? Mechanism?

Back 1

Mannitol
- ↑ Tubular fluid osmolarity
- Produces ↑ urine flow
- ↓ Intracranial / intraocular pressure

Front 2

What are the clinical uses of Mannitol?

Back 2

- Drug overdose
- ↑ Intracranial / intraocular pressure

Front 3

What potential toxicity is associated with Mannitol? Contraindications?

Back 3

- Pulmonary edema
- Dehydration
- Contraindication in anuria and CHF

Front 4

Which drug is a carbonic anhydrase inhibitor? Mechanism?

Back 4

Acetazolamide
- Causes self-limited NaHCO3- diuresis
- ↓ Total body HCO3- stores

Front 5

What are the clinical uses of Acetazolamide?

Back 5

- Glaucoma
- Urinary alkalinization
- Metabolic alkalosis
- Altitude sickness
- Peudotumor cerebri

Front 6

What toxicity is associated with Acetazolamide?

Back 6

- Hyperchloremic metabolic acidosis ("ACID"azolamide causes "ACID"osis)
- Paresthesias
- NH3 toxicity
- Sulfa allergy

Front 7

What are the types of loop diuretics?

Back 7

- Furosemide
- Ethacrynic Acid

Front 8

What is the mechanism of Furosemide?

Back 8

Sulfonamide loop diuretic:
- Inhibits co-transport system (Na+/K+/2Cl-) 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)

Front 9

What are the clinical uses of Furosemide?

Back 9

- Edematous states (CHF, cirrhosis, nephrotic syndrome, pulmonary edema)
- Hypertension
- Hypercalcemia (Loops Lose Calcium)

Front 10

What are the potential toxic side effects of Furosemide?

Back 10

OH DANG!
- Ototoxicity
- Hypokalemia
- Dehydration
- Allergy (sufla)
- Nephritis (interstitial)
- Gout

Front 11

What is the mechanism of Ethacrynic Acid?

Back 11

Loop Diuretic:
- Phenoxyacetic acid derivative (not a sulfonamide)
- Inhibits co-transport system (Na+/K+/2Cl-) 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)

Front 12

What is the clinical use of Ethacrynic Acid?

Back 12

Diuresis in patients allergic to sulfa drugs (Furosemide):
- Edematous states (CHF, cirrhosis, nephrotic syndrome, pulmonary edema)
- Hypertension
- Hypercalcemia (Loops Lose Calcium)

Front 13

What are the side effects of Ethacrynic Acid?

Back 13

- Similar to furosemide (OH DANG: Ototoxicity, Hypokalemia, Dehydration, Nephritis (interstitial), Gout)
- Can cause hyperuricemia - never used in patients with gout

Front 14

What is the mechanism of Hydrochlorothiazide?

Back 14

Thiazide Diuretic:
- Inhibits NaCl reabsorption in early distal tubule
- ↓ Diluting capacity of the nephron
- ↓ Ca2+ excretion

Front 15

What are the clinical uses of Hydrochlorothiazide?

Back 15

- Hypertension
- CHF
- Idiopathic hypercalciuria (↓ Ca2+ excretion)
- Nephrogenic diabetes insipidus
- Osteoporosis (↓ Ca2+ excretion)

Front 16

What are the potential side effects of Hydrochlorothiazide?

Back 16

- Hypokalemic metabolic alkalosis
- Hyponatremia
- Sulfa allergy

Hyper-GLUC:
- HyperGlycemia
- HyperLipidemia
- HyperUricemia
- HyperCalcemia

Front 17

What are the K+ sparing diuretics?

Back 17

- Spironolactone and Eplerenone
- Triamterene
- Amiloride

Front 18

What is the mechanism of the Spironolactone and Eplerenone?

Back 18

K+ Sparing Diuretics:
- Competitive aldosterone antagonists in the cortical collecting tubule

Front 19

What is the mechanism of Triamterene and Amiloride

Back 19

K+ Sparing Diuretics:
- Act on cortical collecting tubule by blocking Na+ channels

Front 20

What are the clinical uses of the K+ sparing diuretics?

Back 20

- Hyperaldosteronism (Spironolactone and Eplerenone are aldosterone receptor antagonists)
- K+ depletion
- CHF

Front 21

What are the potential toxicities of K+ Sparing Diuretics?

Back 21

- Hyperkalemia: can lead to arrhythmia
- Endocrine effects with Spironolactone: eg, gynecomastia, anti-androgen effects

Front 22

How do diuretics affect urine NaCl? Exceptions?

Back 22

↑ urine NaCl, serum NaCl may ↓ as a result
- Exception: Acetazolamide

Front 23

How do diuretics affect urine K+? Exceptions?

Back 23

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

- Exception: K+ sparing diuretics

Front 24

Which diuretics cause acidemia? Mechanism?

Back 24

- Carbonic Anhydrase Inhibitors (Acetazolamide) by ↓ HCO3- reabsorption
- K+ sparing / Aldosterone Antagonists by preventing K+ secretion and H+ secretion; hyperkalemia leads to K+ entering all cells (via H+/K+ exchanger) in exchange for H+ exiting cells)

Front 25

Which diuretics cause alkalemia? Mechanism?

Back 25

Loop diuretics and thiazide diuretics:
- Volume contraction → ↑ AT II → ↑ Na+/H+ exchange in proximal tubule → ↑ HCO3- reabsorption ("contraction alkalosis")
- K+ loss leads to K+ exiting 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"

Front 26

How do diuretics affect urine Ca2+? Mechanism?

Back 26

- ↑ urine Ca2+ with loop diuretics: ↓ paracellular Ca2+ reabsorption → hypocalcemia

- ↓ urine Ca2+ with thiazide diuretics: enhanced paracellular Ca2+ reabsorption in distal tubule

Front 27

What are the types of ACE inhibitors?

Back 27

- Captopril
- Enalapril
- Lisinopril

Front 28

What is the mechanism of ACE inhibitors?

Back 28

- Inhibit ACE → ↓ AT 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

Front 29

What is the mechanism of Angiotensin II Receptor Blockers?

Back 29

Similar effect as ACE-Inhibitors but they don't ↑ bradykinin → ↓ risk of cough and angioedema

Front 30

What are the clinical uses of ACE-inhibitors?

Back 30

- Hypertension
- CHF
- Proteinuria
- Diabetic nephropathy
- Prevent unfavorable heart remodeling as a result of chronic hypertension

Front 31

What toxic events can occur because of ACE-inhibitors?

Back 31

CATCHH:
- Cough
- Angioedema (contraindicated in C1 esterase inhibitor deficiency)
- Teratogen (fetal renal malformations)
- ↑ Creatinine (↓ GFR)
- Hyperkalemia
- Hypotension

Front 32

When should you avoid use of ACE-Inhibitors? Why?

Back 32

- Women of reproductive age (because it is a teratogen)
- Bilateral renal artery stenosis (because will further ↓ GFR → renal failure)