DRUGS ACTING ON THE KIDNEY: DIURETICS AND ANTI-DIURETICS: A TEACHER’S COMPREHENSIVE GUIDE
Welcome, future pharmacologists and healthcare professionals!
The kidneys are vital organs that maintain fluid and electrolyte balance in the body. Drugs acting on the kidney—diuretics and anti-diuretics—are among the most commonly prescribed medications worldwide. Diuretics increase urine output and are used to treat oedema, hypertension, and heart failure. Anti-diuretics decrease urine output and are used to treat diabetes insipidus. As a pharmacology educator with years of experience teaching renal pharmacology, I have observed that students often find this topic challenging due to the various drug classes and their sites of action. Let me tell you: Understanding renal drugs is essential for managing fluid and electrolyte disorders.
In this comprehensive guide, I will walk you through the major classes of diuretics—high efficacy (loop diuretics), medium efficacy (thiazides), weak or adjunctive diuretics—and anti-diuretics. By the end of this article, you will have a thorough understanding of these essential pharmacological agents. Let us begin!
Dpharmguru’s exam insights:
Renal drugs are frequently tested in pharmacology exams. Remember: Diuretics increase urine output—Loop diuretics (Furosemide) act on the thick ascending limb of Loop of Henle; Thiazides act on the distal convoluted tubule; Potassium-sparing diuretics (Spironolactone) act on the collecting duct. Anti-diuretics (Desmopressin) decrease urine output and are used in Diabetes Insipidus. These are classic exam questions!
1. DIURETICS
Diuretics (water pills) promote urine output. They act directly on the kidneys and primarily increase the excretion of water and ions [sodium (Na⁺), chloride (Cl⁻), or bicarbonates (HCO₃⁻)] from the body.
Classification of Diuretics
- High Efficacy Diuretics (Loop Diuretics):
- Sulfamoyl Derivatives: Furosemide, Bumetanide
- Phenoxyacetic Acid Derivatives: Ethacrynic acid
- Organomercurials: Mersalyl
- Medium Efficacy Diuretics (Thiazides):
- Thiazides: Chlorothiazide, Hydrochlorothiazide, Benzthiazide, Hydroflumethiazide, Clopamide
- Thiazide-like: Chlorthalidone, Metolazone, Xipamide, Indapamide
- Weak or Adjunctive Diuretics:
- Carbonic Anhydrase Inhibitors: Acetazolamide
- Potassium Sparing Diuretics: Spironolactone, Triamterene, Amiloride
- Osmotic Diuretics: Mannitol, Isosorbide, Glycerol
- Xanthines: Theophylline
High Efficacy Diuretics (Loop Diuretics) — Furosemide
Site of Action: Thick ascending limb of the loop of Henle. They are the most effective among all diuretics—also known as high ceiling diuretics or Na⁺K⁺2Cl⁻ co-transporter inhibitors.
Pharmacological Action: Inhibits water reabsorption by blocking the sodium-potassium-chloride cotransporter (Na⁺K⁺2Cl⁻) in the thick ascending limb of the loop of Henle. Responsible for 25% of sodium reabsorption.
Dose: 20–80 mg IV over 1–2 minutes for treatment of oedema.
Indications: Acute pulmonary oedema, refractory oedema (CHF, renal disease), hypercalcaemia, hyperkalaemia.
Contraindications: Anuria, hypersensitivity, allergy to sulpha drugs, hypokalaemia, severe hyponatraemia, hypotension, hepatic coma.
Adverse Effects:
- Renal: Hypokalaemia, metabolic hypochloraemic alkalosis, hypocalcaemia, hypovolaemia, hypotension, hyperuricaemia (gout), hypomagnesaemia
- Extra-renal: Dose-related reversible ototoxicity (hearing loss), pancreatitis, hypersensitivity, myalgia, GIT upset, hepatic encephalopathy
Medium Efficacy Diuretics (Thiazides)
Site of Action: Distal convoluted tubule. They inhibit the sodium-chloride transporter, reabsorbing about 5% of filtered sodium.
| Drug | Daily Dose (mg) | Duration of Action (hrs) |
|---|---|---|
| Hydrochlorothiazide | 12.5–100 | 5–15 |
| Benzthiazide | 25–100 | 12–18 |
| Hydroflumethiazide | 25–100 | 12–18 |
| Chlorthalidone | 50–100 | 48 |
| Metolazone | 5–20 | 8–10 |
| Xipamide | 20–40 | 5–8 |
| Indapamide | 2.5–5 | 12–24 |
| Clopamide | 10–60 | 12–18 |
Indications: Oedema (cardiac, hepatic, renal), hypertension (mild), calcium nephrolithiasis, diabetes insipidus (nephrogenic), bromide intoxication.
Contraindications: Sensitivity to sulpha drugs—use cautiously.
Adverse Effects: Hyponatraemia, hypochloraemic metabolic alkalosis, hypokalaemia, weakness, fatigability, paraesthesia, glycosuria, hyperglycaemia, hyperuricaemia (gout), hyperlipidaemia, hypersensitivity, hepatic encephalopathy.
Weak or Adjunctive Diuretics
Carbonic Anhydrase Inhibitors (Acetazolamide)
Pharmacological Action: Inhibits transport of bicarbonate out of the proximal convoluted tubule, leading to less sodium reabsorption and greater sodium, bicarbonate, and water loss.
Indications: Glaucoma, alkalinising urine, epilepsy (adjuvant), acute mountain sickness.
Adverse Effects: Acidosis, hypokalaemia, drowsiness, fatigue, abdominal discomfort, hypersensitivity (fever, rashes), rarely bone marrow depression.
Potassium Sparing Diuretics
Examples: Spironolactone (aldosterone antagonist), Triamterene, Amiloride
Pharmacological Action: Interfere with sodium-potassium exchange in the distal convoluted tubule (amiloride, triamterene) or antagonise aldosterone receptors (spironolactone).
Indications: Used with thiazides or loop diuretics to prevent hypokalaemia.
Adverse Effects: Hyperkalaemia (risk increased with ACE inhibitors and renal impairment).
Osmotic Diuretics (Mannitol)
Pharmacological Action: Increase osmolality of blood and renal filtrate, inhibiting sodium and water reabsorption.
Indications: Reduction of intracranial pressure (cerebral oedema), intraocular pressure (glaucoma), prevention of oliguria or anuria.
Adverse Effects: Increased blood volume, pulmonary oedema, decreased osmolality, hyponatraemia.
2. ANTI-DIURETICS
Anti-diuretics decrease the volume of urine. These agents suppress urine formation and are primarily indicated for patients with Diabetes Insipidus (DI).
Classification of Anti-diuretics
- Antidiuretic Hormone (ADH or Vasopressin): Desmopressin, Lypressin, Terlipressin
- Thiazide Diuretics: Amiloride
- Miscellaneous: Indomethacin, Chlorpropamide, Carbamazepine
Vasopressin Analogues
ADH (Arginine Vasopressin) is secreted by the neurohypophysis (posterior pituitary).
- Lypressin: 8-lysine vasopressin analogue; less potent than AVP; acts on V1 and V2 receptors; duration 4–6 hours.
- Desmopressin: Synthetic peptide; selective V₂ agonist; negligible vasoconstrictor action—Drug of Choice for Diabetes Insipidus.
Pharmacological Actions:
- Kidney: Increases permeability to water in collecting duct cells, allowing water diffusion from lumen to interstitium.
- Blood Vessels: Constricts blood vessels via V₁ receptors (vasopressin).
- Uterus: Contraction via oxytocin receptors.
- CNS: Does not cross BBB; acts as peptide neurotransmitter in brain and spinal cord.
Indications (V₂ Actions): Diabetes Insipidus (neurogenic), bedwetting in children, nocturia in adults, renal concentration test, haemophilia, Von Willebrand’s disease.
Indications (V₁ Actions): Bleeding oesophageal varices, before abdominal radiography.
Contraindications: Ischaemic heart disease, hypertension, chronic nephritis, psychogenic polydipsia.
Adverse Effects: Flushing, transient headache, nasal irritation, congestion, rhinitis, ulceration, epistaxis, belching, nausea, abdominal cramps, pallor, urge to defecate, backache (uterine contractions).
Thiazide Diuretics as Anti-diuretic Agents (Amiloride)
Pharmacological Action: Causes kidneys to get rid of extra water and salt while reducing potassium loss.
Dose: 5 mg orally once a day.