Renal: Drugs

Question 1

• Works at the Proximal Convoluted Tubule
• Mechanism:
  
  • Carbonic anhydrase inhibitor
  • Causes self limited NaHCO₃ diuresis and ↓ total-body HCO₃^- stores
• Tx: Glaucoma, Urinary alkalinization, Metabolic alkalosis, Altitude sickness (↓ CSF), Pseudotumor cerebri
• SEx: Hyperchloremic metabolic acidosis after several days of admin., Renal Stones, Potassium loss, Parasthesias, NH₃ toxicity, Sulfa allergy
• Contra: Hepatic cirrhosis (NH₄⁺ accumulation)
• ACID azolamide causes ACIDosis

Answer 1

Acetazolamide

Question 2

• Works at the Thin Descending Tubule
• metabolically inert hexose sugar
• Mechanism:
  
  • Osmotic diuretic, ↑ Tubular fluid osmolarity, Producing ↑ urine flow (lowers resistance)
  • ↓ Intracranial / Intraocular pressure
  • ↑ RPF
• Tx: Acute renal failure, Drug overdose, ↑Intracranial / Intraocular pressure
• SEx: Pulmonary edema, Dehydration, Hypernatremia, Extracellular volume expansion
• Contraindicated in Anuria, CHF

Answer 2

Mannitol

Question 3

• Works on the Thick Ascending Limb
• Mechanism:
  
  • Sulfonamide loop diuretic. Inhibits cotransport system (Na⁺/K⁺/2Cl^-) - Limb 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
• Tx: Edematous states (CHF, Cirrhosis, Nephrotic syndrome, Pulmonary edema), HTN, Hypercalcemia
• SEx: Ototoxicity, Hypokalemia, Dehydration, Allergy (sulfa), Nephritis (interstitial), Gout - OH DANG!

Answer 3

Loop Diuretics

Question 4

• Works on the Thick Ascending Limb
• Mechanism:
  
  • Phenoxyacetic acid derivative (Not a Sulfonamide)
  • Essentially same action as Furosemide
• Tx: Diuresis in patients allergic to Sulfa Drugs
• SEx: Similar to Furosimide; can cause Hyperuricemia, NEVER use to treat Gout

Answer 4

Ethacrynic Acid

Question 5

• Works on the Distal Convoluted Tubule
• Mechanism: Thiazide diuretic. Inhibits NaCl reabsorption in early Distal Tubule. ↓ Diluting capacity of the Nephron. ↓ Ca²⁺ excretion
• Tx: Hypertension, CHF, Idiopathic Hypercalciuria, Nephrogenic Diabetes insipidus, Osteoporosis
• SEx: HyperGLUCs
  
  • Hypokalemic metabolic alkalosis, Hyponatremia, HyperGlycemia, HyperLipidemia, HyperUricemia, and HyperCalcemia, Sulfa drugs

Answer 5

Hydrochlorothiazide

Question 6

• Works on the Collecting Tubule
• Mechanism:
  
  • Spironolactone and Eplerenone are competitive Aldoserone receptor antagonsits in the Cortical collecting tubule
  • Triamterene and Amiloride act at the same part of the Tubule by blocking Na⁺ channels in the CCT
• Tx: Hyperaldosteronism, K⁺ depletion, CHF
• SEx: Hyperkalemia (can lead to arrhythmias) Endocrine effects w/ Spironolactone (e.g. Gyncomastia, Antiandrogen effects)

Answer 6

K⁺ - Sparing Diuretics

Question 7

Electrolyte changes due to Urine NaCl?

Answer 7

• ↑ all diuretics except Acetazolamide
• Serum Nacl may ↓ as a result

Question 8

Diuretic electrolyte changed due to Urine K⁺?

Answer 8

• ↑ w/ Loop and Thiazide diuretics
• Serum K⁺ may ↓ as a result

Question 9

Diuretic electrolye changes due to ↓ Blood pH?

Answer 9

• ↓ 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 10

Diuretic electrolyte changes due to ↑ Blood pH?

Answer 10

• ↑ 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 11

Diuretic electrolyte changes due to Ca²⁺?

Answer 11

• ↑ w/ Loop Diuretics:
  
  • ↓ Paracellular Ca²⁺ reabsorption -> Hypocalcemia​
• ↓ w/ Thiazides:
  
  • Enhanced paracellular Ca2+ reabsorption in Distal Convoluted Tubule

Question 12

• Mechanism:
  
  • 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
• Tx: Hypertension, CHF, Proteinuria, Diabetic nephropathy. Prevent unfavorable heart remodeling as a result of Chronic Hypertension
• SEx: Cough, Angioedema (contraindicated in C1 esterase inhibitor deficiency), Teratogen (fetal renal malformations), ↑ Creatinine (↓ GFR), Hyperkalemia, and Hypotension - CATCHH
  
  • Avoid in bilateral Renal artery stenosis, because ACE inhibitors will further ↓ GFR -> Renal Failure

Answer 12

ACE Inhibitors

• Captopril
• Enalapril
• Lisinopril
• Angiotensin II receptor blockers (-sartans) have effects similar to ACE inhibitors but do not ↑ Bradykinin -> ↓ Risk of cough or Angioedema