1. DIURETICS
   1. CLASSIFICATION
      1. Drugs acting at proximal convoluted tubule (PCT) (Site 1)
         1. Carbonic anhydrase inhibitor: Acetazolamide.
      2. 2. Drugs acting at thick ascending limb of loop of Henle (Site 2)
         1. Loop diuretics: Furosemide, bumetanide, torsemide.
      3. 3. Drugs acting at early distal tubule (Site 3)
         1. Thiazides: Chlorothiazide, hydrochlorothiazide, benzthiazide, polythiazide.
         2. Thiazide like diuretics: Chlorthalidone, indapamide, metolazone.
      4. 4. Drugs acting at late distal tubule and collecting duct (CD) (Site 4)
         1. Aldosterone antagonist: Spironolactone.
         2. Direct inhibitors of Na+ channels: Amiloride, triamterene.
      5. 5. Drugs acting on entire nephron (main site of action is loop of Henle)
         1. Osmotic diuretics: Mannitol, glycerol, isosorbide.
2. ANTI DIURETICS
   1. VASOPRESSIN
   2. Vasopressin Analogues
      1. Desmopressin
         1. selective V2-receptor agonist and is more potent than vasopressin as an antidiuretic.
         2. It has negligible vasoconstrictor action. It is administered by oral, nasal and parenteral routes.
      2. lypressin
         1. acts on both V1- and V2-receptors.
         2. It is less potent but longer acting than vasopressin.
         3. is administered parenterally.
      3. Uses
         1. to V1-receptor mediated actions
         2. For emergency control of bleeding oesophageal varices:
         3. ADH controls bleeding by constricting mesenteric blood vessels.
         4. 2. Due to V2-receptor-mediated actions
         5. a. Neurogenic diabetes insipidus (DI)
         6. Haemophilia and von Willebrand’s disease:
         7. Primary nocturnal enuresis:
      4. Adverse effects
         1. Nausea, vomiting, diarrhoea, belching and abdominal cramps.
         2. 2. Backache is due to uterine contraction.
         3. 3. Intranasal administration may cause local irritation and ulceration.
         4. 4. Fluid retention and hyponatraemia can occur.
3. Acetazolamide
   1. uses
      1. Glaucoma: decrease intraocular pressure (IOP) by reducing the formation of aqueous humour.
      2. used in acute congestive glaucoma by oral and IV Routes
      3. used in chronic simple glaucoma
      4. 2. To alkalinize urine in acidic drug poisoning.
      5. 3. Acute mountain sickness can be used both for symptomatic relief and prophylaxis
      6. 4. Miscellaneous: As an adjuvant in epilepsy; treatment of metabolic alkalosis resulting from use of
      7. diuretics in congestive heart failure.
   2. Adverse effect
      1. hypersensitivity reactions (skin rashes, fever, nephritis, etc.), headache, drowsiness,
      2. paraesthesia, hypokalaemia, metabolic acidosis and renal stones.
   3. CONTRAINDICATIONs
      1. Liver disease: Hepatic coma may be precipitated in patients with cirrhosis due to decreased excretion of ammonia (NH3) in alkaline urine.
      2. 2. Chronic obstructive pulmonary disease (COPD): Worsening of metabolic acidosis is seen in patients with chronic obstructive pulmonary disease.
4. Osmotic diuretics
   1. MOA
   2. USES
      1. Mannitol is used to prevent acute renal shutdown in shock, cardiovascular surgery, haemolytic
      2. transfusion reactions, etc.
      3. used to reduce elevated intracranial tension (ICT) following head injury or tumour.
      4. reduce elevated IOP
      5. in acute congestive glaucoma
   3. Adverse effects
      1. cause marked expansion of ECF volume,
      2. which can lead to pulmonary oedema.
      3. 2. Headache, nausea and vomiting may occur.
      4. 3. Glycerol can cause hyperglycaemia.
   4. CONTRAINDICATIONs
      1. congestive cardiac failure (CCF) and pulmonary oedema
      2. chronic oedema
      3. anuric renal disease and active intracranial bleeding.
5. LOOP DIURETICS
   1. USES
      1. During the initial stages of renal, hepatic and cardiac oedema, loop diuretics are preferred.
      2. 2. Intravenous furosemide is used in hypercalcaemia as it promotes excretion of Ca2+ in urine.
      3. 3. Acute pulmonary oedema
      4. used in cerebral oedema but i.v. mannitol is the preferred drug.
      5. 5. Hypertension: Loop diuretics can be used in hypertension associated with CCF/renal failure
      6. in hypertensive emergencies.
      7. Furosemide is not preferred in uncomplicated primary hypertension because of its short duration of action.
      8. 6. Loop diuretics can be used in mild hyperkalaemia.
   2. ADVERSE EFFECTS
      1. Hypokalemia
      2. Hyponatremia
      3. Hypokalaemic metabolic alkalosis
      4. Hypocalcaemia and hypomagnesaemia
      5. Hyperglycemia
      6. Hyperlipidemia
      7. hyperuricemia
      8. Ototoxicity manifests as deafness, vertigo and tinnitus
6. Thiazides
   1. MOA
   2. USES
      1. Hypertension: Thiazides are used in the treatment of essential hypertension
      2. 2. Heart failure: Thiazides are used for mild-to-moderate cases of heart failure
      3. 3. Hypercalciuria: Thiazides are used in calcium nephrolithiasis as they reduce the urinary excretion
      4. 4. Diabetes insipidus
   3. Adverse effects
      1. hypokalaemia, hyponatraemia, metabolic
      2. alkalosis, hypomagnesaemia and hypercalcaemia
      3. may cause impotence;
7. Spironolactone
   1. USES
      1. In oedematous conditions associated with secondary hyperaldosteronism (congestive cardiac failure,
      2. hepatic cirrhosis and nephrotic syndrome).
      3. 2. Spironolactone is often used with thiazides/loop diuretics to compensate K+ loss.
      4. 3. Resistant hypertension due to primary hyperaldosteronism (Conn’s syndrome)
   2. Adverse effects
      1. Hyperkalaemia is the major adverse effect of aldosterone antagonists.
      2. more risk in patients with renal disease or in those receiving ACE inhibitors, ARBs, -blockers, NSAIDs, etc.
      3. Other adverse effects include nausea, vomiting, diarrhoea, peptic ulcer, drowsiness, mental confusion,
      4. menstrual disturbances, gynaecomastia, decreased libido and impotence.
8. OTHER KEY POINTS
   1. Regularly monitor the weight of patients on diuretics.
   2. Administer diuretics usually in the morning.
   3. Monitor diet and educate patient about food rich in potassium (banana, fruit juice, tender coconut water,
   4. Monitor for possible drug interactions if patient is also on ACE inhibitors, lithium, digoxin, etc.
   5. Administer syrup of potassium chloride diluted in a tumbler full of water to avoid intestinal ulceration.
   6. Slowly administer i.v. potassium chloride, as it has a cardiac-depressant effect.
   7. Monitor serum electrolytes, BP and pulse when the patient is on diuretics.