Therapeutic drugs

• Kidney functions

  • Extracellular fluid homeostasis
  • Regulating fluid volume
  • Regulating concentration of electrolytes (e.g., sodium, potassium, calcium)
  • Acid-base balance
  • Filtering wasteproducts of metabolism (e.g., urea)
  • Secreting hormones (EPO)
  • Blood pressure regulation (through RAAS)
  • Synthesis of activated vitamin D (calcitriol)
• Diuretics

  Drugs that increase excretion of $Na^+, Cl^-, H_2O$ from renal tubules, increasing urinary flow
• Indications for diuretics

  • Treatment of conditions where there is accumulation of excess sodium and fluid in the body (e.g., heart failure, renal failure, liver failure and hypertension)
• Types of diuretics

  • Loop (furosemide, bumetanide)
  • Thiazide and thiazide-like (bendroflumethiazide, chlortalidone)
  • Potassium-sparing (spironolactone, amiloride)
  • Osmotic (mannitol)
  • Carbonic anhydrase (acetazolamide)
• Loop diuretics

  Act of the thick ascending limb in the loop of Henle, inhibit the resorption of around 25% of sodium and chloride ions
• Thiazide and thiazide-like diuretics

  Act of DCT, inhibit the resorption of 5-10% of sodium chloride
• Potassium-sparing diuretics

  Act on the distal end of DCT and early end of collecting duct, inhibit the resorption of 2-3% of sodium ions in exchange for either potassium or hydrogen ions
• Osmotic diuretics

  Are small molecules filtered at the glomerulus, but not resorbed, thus changing the osmotic pressure, and preventing water reabsorption (occasionally used to treat cerebral oedema in intensive care)
• Carbonic anhydrase inhibitors

  Reduce production of protons, and bicarb ions, indirectly inhibiting sodium and chloride resorption in the PCT (rarely used)
• ACE inhibitors

  Inhibit ACE resulting in vasodilation, and inhibits the release of aldosterone (decreases blood pressure, indicated more for heart failure)
• Angiotensin receptor antagonists

  Block angiotensin 2 receptors, resulting in vasodilation (decreases blood pressure, indicated more for heart failure)
• SGLT-2 inhibitors

  Inhibit the co-transporter that resorbs glucose and sodium in the PCT/early LoH, increasing urinary excretion of glucose (indicated for T2DM)
• Uricosurics

  Inhibit resorption of uric acid in the PCT (indicated for long-term prevention of gout)
• Probenecid

  Historically used for inhibiting excretion of penicillins
• Exogenous PTH

  Used for calcium resorption in DCT
• Vasopressin analogues

  Used to prevent dehydration and polyuria (from DI, DM), artificial ADH
• Vasopressin inhibitors

  Inhibit the action of ADH when there is excess of it (from SIADH)
• EPO

  Used to treat anaemia, by stimulating RBC synthesis
• Vitamin D

  Exogenous active vitamin D
• Sodium bicarbonate


  Used to prevent metabolic acidosis
• angiotensin-converting enzyme inhibitors include ramipril and lisinopril
• angiotensin receptor antagonists include losartan and candesartan
• drugs acting on glomerular function:

  • ACE inhibitors
  • ARB's
• drugs acting on PCT include:

  • SGLT-2 inhibitors
  • Uricosuric
• sodium-glucose co-transporter-2 (SGLT-2) inhibitors include canagliflozin and dapagliflozin
• Uricosuric include febuxostat and sulfinpyrazone
• drugs acting on DCT:

  • thiazide diuretics
  • exogenous PTH (for calcium resorption)
• drugs acting on collecting duct:

  • vasopressin analogues
  • vasopressin inhibitors
• vasopressin analogues include Desmopressin
• vasopressin analogues are used to prevent dehydration and polyuria (from DI, DM), artificial ADH
• vasopressin inhibitors include Demeclocycline - is a tricyclic antibody, Tolvaotan is a specific vasopressin V2 receptor antagonist
• vasopressin inhibitors inhibit the action of ADH when there is excess of it ( from SIADH)
• there are 3 important kinds of drugs that are give to replace endogenous products synthesised by kidneys:

  • EPO (epoetin beta, darbepoetin alfa) - used to treat anaemia, by stimulating RBC synthesis
  • Vitamin D (alfacalcidol or calcitriol) - exogenous active vitamin D
  • sodium bicarbonate - used to prevent metabolic acidosis