diuretics 1

• Diuretics


  Drugs which cause a net loss of sodium and water from the body by an action on the kidney
• Classification of diuretics according to site of action

  • Extrarenal diuretics (outside the kidney)
  • Renal diuretics
• Extrarenal diuretics


  • Inhibiting the release of antidiuretic hormone water
  • Increasing the cardiac output and increasing renal blood flow digitalis
• Renal diuretics


  • Diuretics increase urine production by acting on the kidney
• Types of renal diuretics

  • Natriuretic
  • Osmotic diuretics
• Natriuretic diuretics


  • Produce diuresis, associated with increased sodium ion (Na+) excretion which results in a concomitant loss of water and a reduction in extracellular volume
• Natriuretic diuretics by natriuretic capacity

  • High efficacy
  • Moderate efficacy
  • Low efficacy
• High efficacy natriuretic diuretics

  • Cause 15-25% of filtered sodium to be excreted, remain effective at glomerular filtration rates (GFR) below 10 ml/min, act mainly on the Medullary part of thick ascending loop of Henle
• Moderate efficacy natriuretic diuretics


  • Cause 5-10% of filtered sodium to be excreted, ineffective if the glomerular filtration rate below 20 ml/min, act mainly on the cortical diluting segment
• Low efficacy natriuretic diuretics

  • Cause 5% of filtered sodium to be excreted, usually combined with more efficacious diuretics, act mainly on the distal part of distal convoluted tubules and collecting duct
• Osmotic diuretics


  Osmotic agents that affect water balance directly
• Osmotic diuretics


  • Mannitol
• Thiazide diuretics


  Chlorothiazide, hydrochlorothiazide
• Mechanism of action of thiazide diuretics


  1. Act mainly on the early segment of the distal tubule (cortical diluting segment)

  2. Decrease sodium reabsorption by inhibiting the Na+/Cl- cotransporter

  3. Increase excretion of Cl-, Na+ and accompanying H2O

  4. Increase Na+ exchange with K+, increasing its excretion and causing hypokalaemia and metabolic alkalosis
• Pharmacological actions of thiazide diuretics

  • Increase renal excretion of Na+, Cl-, K+, HCO3- and water
  • Increase Ca2+ reabsorption in distal tubules resulting in decrease Ca2+ excretion
  • Decrease uric acid excretion due to competition inhibition of the tubular transport of organic acids
  • Increase the urinary outflow of magnesium
  • Decrease glomerular filtration rate due to decrease renal blood flow through a direct action on renal vasculature
  • Increase the renal excretion of bromide and iodide
• Paradoxical antidiuretic effect of thiazides in diabetes insipidus

  • Cause mild sodium and volume depletion, increase Na+ load passing to the distal part of distal tubule and collecting tubules, decrease glomerular filtration rate, increase the sensitivity of ADH receptors in the renal tubules
• Antihypertensive effect of thiazides

  • Reduction in plasma volume and stroke volume decreases cardiac output and BP
  • Increase diameter of blood vessels by mobilizing sodium and water from arteriolar wall
  • Alter intracellular Na+, K+, Ca2+ and Mg2+ concentrations which may decrease vascular response to pressor substances and increase vascular response to depressor substances
  • Cause direct relaxation of vascular smooth muscle
• Therapeutic uses of thiazide diuretics

  • Treatment of edema and ascites
  • Essential hypertension
  • Treatment of nephrogenic diabetes insipidus
  • Treatment of hypercalciuria associated with recurrent renal calcium stones
  • Protective effect in patients at risk for osteoporosis and long bone fracture
• Adverse effects of thiazide diuretics

  • Hypokalaemia and metabolic alkalosis
  • Hypomagnesemia --> cardiac arrhythmias
  • Hyperuricemia
  • Hyperglycemia
  • Hypercalcemia
  • Increase in total cholesterol and triglycerides
  • Hyponatraemia
  • Hypersensitivity reactions
  • Precipitate encephalopathy in hepatic insufficiency
  • Anaemia, gastric irritation, male impotence, dizziness, vertigo, paraesthesia, and fatigability
• Contraindications of thiazide diuretics

  • Diabetes mellitus
  • Gout
  • Decompensated liver cirrhosis
  • Hypersensitivity to thiazide
  • Hyperlipidemia
  • Renal impairment
• Drug interactions of thiazide diuretics


  • May precipitate digitalis toxicity
  • Severe hypokalaemia with corticosteroids
  • Reduce the effect on blood sugar produced by antidiabetic drugs
  • Risk of thrombocytopenia with purpura with trimethoprim and sulphamethoxazole
  • Increase the skeletal muscle relaxant activity of tubocurarine and gallamine
• Natriuretic diuretics


  A type of diuretic that increases sodium and water excretion by promoting natriuresis. Examples include furosemide, bumetanide, torsemide, ethacrynic acid, spironolactone, and amiloride.
• Natriuretic capacity


  The ability of a natriuretic diuretic to promote sodium excretion. Natriuretic diuretics can be classified as high, moderate, or low efficacy based on their natriuretic capacity.
• Low efficacy natriuretic diuretics


  These natriuretic diuretics have a weak ability to promote sodium excretion. Examples include spironolactone and amiloride.
• Moderate efficacy natriuretic diuretics

  These natriuretic diuretics have a moderate ability to promote sodium excretion. Examples include torsemide and ethacrynic acid.
• High efficacy natriuretic diuretics


  These natriuretic diuretics have a strong ability to promote sodium excretion. Examples include furosemide and bumetanide.
• Thiazide diuretics


  A type of diuretic that works by inhibiting the sodium-chloride cotransporter in the distal convoluted tubule of the nephron in the kidney. Examples include hydrochlorothiazide and chlorthalidone.
• Decreased intravascular volume


  A mechanism by which thiazide diuretics can decrease the glomerular filtration rate (GFR) and renal blood flow. This occurs because the increase in sodium and water excretion caused by thiazide diuretics can lead to a decrease in intravascular volume, which can cause a decrease in renal blood flow and GFR.
• Tubuloglomerular feedback


  A mechanism by which thiazide diuretics can decrease the GFR and renal blood flow. This occurs because thiazide diuretics can increase the delivery of sodium to the macula densa, which can trigger tubuloglomerular feedback and cause the afferent arteriole to constrict, decreasing renal blood flow and GFR.
• thiazide cause alteration in the concentration of Na Ca k and Mg intracellular concentrations which may: decrease vascular response to repressor substance and increase vascular response to depressor substances
• Increased blood sugar levels


  A potential side effect of thiazide diuretics, which can occur due to decreased insulin secretion and increased glucose production. Patients taking thiazide diuretics should be monitored closely for signs of increased blood sugar levels, such as frequent urination, increased thirst, and fatigue.
• Dehydration


  A potential side effect of thiazide diuretics, which can occur due to increased urine output and decreased intravascular volume. Patients taking thiazide diuretics should be monitored closely for signs of dehydration, such as dry mouth, thirst, and dizziness.
• Electrolyte imbalances


  A potential side effect of thiazide diuretics, which can occur due to increased urine output and decreased intravascular volume. Patients taking thiazide diuretics should be monitored closely for signs of electrolyte imbalances, such as muscle cramps, weakness, and irregular heart rhythms.
• Preventing kidney stones


  Thiazide diuretics can be used to prevent the formation of kidney stones, which are small, hard mineral deposits that can form in the kidneys. They work by decreasing urine calcium levels, which can help to prevent the formation of calcium-based kidney stones.
• Edema


  An abnormal accumulation of fluid in the body. Thiazide diuretics can be used to treat edema by increasing urine output and decreasing intravascular volume, which can help to reduce fluid accumulation.
• Chronic kidney disease


  A medical condition in which the kidneys are damaged or injured over time. Thiazide diuretics can be used to treat chronic kidney disease by decreasing intravascular volume and reducing the workload on the kidneys.
• Hypertension


  A medical condition in which blood pressure is persistently elevated. Thiazide diuretics are often used as first-line therapy for the treatment of hypertension, either alone or in combination with other antihypertensive medications.
• Heart failure

  A medical condition in which the heart is unable to pump blood effectively. Thiazide diuretics can be used to treat heart failure by decreasing intravascular volume and reducing the workload on the heart.