drugs and the kidney

Question 1

what is the role of the kidney in drug excretion ?

Answer 1

• The kidney is the most important organ for eliminating drugs from body
• Most are metabolised by the liver to an inactive compound that can be excreted by kidney
• Polar drugs or metabolites (water soluble, partially ionized) are excreted via specialized transporters (mainly PT)

Question 2

what are diuretics ?

Answer 2

• Increase urine output (diuresis)
• May also increase electrolyte excretion (Na, natriuresis; K, kaliuresis)
• Very important drugs, e.g.,
  Acute pulmonary oedema, heart failure (reduce ECF volume), Hypertension

Question 3

what are the classes of diuretics ?

Answer 3

Question 4

describe osmotic diuretics

Answer 4

• Example: mannitol
• Freely filtered but not reabsorbed
• Dilution of DT fluid impaired
• Decreased gradient for water reabsorption
• Commonly used to treat cerebral oedema
• Does not cross blood-brain barrier
• Creates osmotic gradient for withdrawal of * water from cerebrospinal fluid to plasma

Question 5

describe carbonic anhydrase inhibitors

Answer 5

• Example: acetazolamide
• Mild diuretics
• Inhibit carbonic anhydrase enzyme, which catalyzes the conversion of CO₂ and H₂O to HCO₃⁻ and H⁺
• Decrease HCO₃⁻ reabsorption in the proximal convoluted tubule
• Increase excretion of bicarbonate (HCO₃⁻), sodium (Na⁺), water, and potassium (K⁺)
• Lead to mild metabolic acidosis due to loss of bicarbonate
• Reduce intraocular pressure (used in glaucoma) by decreasing aqueous humor production
• Reduce renal acidification and promote urine alkalinization

Question 6

describe loop diuretics

Answer 6

• Example: frusemide
• Powerful diuretics
• Inhibit Na/K/2Cl cotransporter in thick ascending limb
• Impedes concentration of medullary interstitial fluid
• Reduced osmotic drive for ADH-mediated water reabsorption
  Side effects
• Significant loss of K: hypokalemia

Question 7

describe thiazide diuretics

Answer 7

• Moderately powerful
• Inhibit Na/Cl cotransporter in distal tubule
• Impedes dilution of tubular fluid
• Reduced osmotic drive for ADH-mediated water reabsorption

Side effects
* Significant loss of K: hypokalemia
* Hypercalcemia (Increased Ca/Na exchanger)

Question 8

describe K sparing diuretics

Answer 8

• Weak diuretic action
• Cause potassium (K) retention, counteracting K loss caused by loop diuretics
• Act at the end of the distal convoluted tubule (DCT) and collecting duct
  Amiloride:
• Blocks Epithelial Sodium Channels (ENaC)
  Spironolactone:
• Aldosterone antagonist
• Used to treat volume overload in heart failure

Question 9

what are the uses of diuretics ?

Answer 9

Thiazide
* Have been first-line hypertension treatment for decades
* No longer first line in NHS (see NICE guidelines) but may be 2nd or 3rd
* Low doses effective for hypertension
* Higher doses may be used for volume overload (e.g. mild to moderate HF)

Loop
* Severe volume overload (e.g. pulmonary oedema due to LV failure)

Potassium sparing
* May supplement thiazide or loop to counter hypokalemia
* Heart failure
* Aldosterone antagonists may be used to control hyperaldosteronism

Question 10

what are a recent class of drugs with mild diuretic action ?

Answer 10

• Secondary active transport mechanism
• SGLT1: Responsible for glucose absorption in the gut
• SGLT1 & SGLT2: Involved in glucose reabsorption from the kidney (proximal convoluted tubule, PCT)

SGLT-2 inhibitors are used to treat hyperglycemia by:
* Impairing glucose reabsorption
* Allowing more glucose to remain in the tubular fluid
* Lowering plasma glucose concentration
* Causing mild osmotic diuresis