DIURETICS

Drugs

Dosage

MOA

ADR

USES

Loop Diuretics (Furosemi de)

• 40-100 mg up to 2 gm orally IM or IV

• It is secreted from PT by organic anion transport and reaches AscLH where it acts from luminal side
• Major site of actin is the thick AscLH (therefore called loop diuretics) where furosemide inhibits Na⁺-K⁺-2Cl^– cotransport
• K⁺ excretion is increased mainly due to high Na⁺ load reaching DT
• However at equinatriuretic doses, K⁺ loss is less than with thiazide
• Furosemide increases Ca²⁺ and Mg²⁺ excretion

• Hypokalemia: prevented by-
  • High dietary intake
  • Supplements of KCl
  • Concurrent use of K⁺ sparing diuretics
• Acute saline depletion- cause dehydration and marked fall in BP
• Dilutional hyponatremia
• Hearing loss
• GIT- N, V, D
• CNS- Headache, giddiness, weakness, paresthesia, impotence
• Allergic manifestations- Rashes, photosensitivity, blood dyscrasias
• Hyperuricemia- lower incidence than thiazide
• Hyperglycemia and hyperlipidemia
• Hypocalcemia
• Magnesium depletion
• Brisk diuresis in cirrhotic patient- precipitate mental disturbances and hepatic encephalopathy

• Edema- of any origin cardiac, hepatic or renal
• Acute pulmonary edema (acute LVF, following MI)
• Cerebral edema
• Hypertension
• Hypercalcemia of

malignancy

• Along with blood transfusion in severe anemia, to prevent volume overload

Amiloride

/Triamter ene

• 5-10 mg/day

• Luminal membrane of late DT and CD cells express a distinct amiloride sensitive Na+ channel
• Amiloride and triamterene block luminal Na+ channel and indirectly inhibit K+ excretion
• They increases excretion of Na+

and Cl-

• Hyperkalemia
• Diarrhea
• Dry mouth
• Skin rash

• Edema disorders with diuretics
• Pseudo-aldosteronism

Thiazide diuretics

• Hydrochloro thiazide- 12.5-50 mg OD

• Secreted via PT through organic acid secretory pathway; reach DT along with tubular fluid
• Primary site of action in the cortical diluting segment or the early DT; here they inhibit Na⁺-Cl^– symport at the luminal membrane
• Under thiazide action, increased amount of Na+ is presented to distal nephron, more of it exchanges with K⁺ -> urinary K⁺ excretion is increased parallel to natriuretic response
• They decreases Ca²⁺ and increases Mg²⁺ excretion

• Furosemide’s plus:
• No-Hearing loss
• Hyperuricemia- More incidence with thiazide
• Hypercalcemia
• Precipitate renal or hepatic failure

• Edema- mild to moderate cases
• Hypertension
• Diabetes insipidus
• Hyperalciuria
• Chlorthalidone- used in correction of hypocalcemia due to hypoparathyroidism

Acetazolamid e

• 250 mg OD/BD

• It is sulphonamide derivative which noncompetitively but reversibly inhibits Case (type II) in PT cells resulting is slowing of hydration of CO₂-> decreased availability of H⁺ to exchange with luminal Na⁺ through Na⁺-H⁺ antiporter.
• HCO₃ cannot be reabsorbed and is lost in

–

urine; so patient will develop metabolic acidosis.

• Due to excess H+ now available for exchange distally. Hence it is self-limiting diuretic

• Metabolic Acidosis
• Hypokalemia
• Drowsiness
• Paresthesia
• Fatigue
• Abdominal discomfort
• Hypersensitivity- fever, rashes
• BM depression
• Liver ds.- Precipitate Hepatic coma so contraindicated

• Due to self-limiting action, production of acidosis and hypokalemia not used as diuretics
• Glaucoma
• To alkalinize urine- UTI, certain acidic drug poisoning
• Acute mountain sickness- Symptomatic relief and prophylaxis
• Periodic paralysis
• Resistant epilepsy- Decreases CSF production

Mannitol

• Not

absorbed orally; given IV

• 25%

solution 1.5-2

gm/kg rapidly IV 100ml, 8

hr. ly

• On IV administration it is freely filtered at glomeruli and undergoes limited reabsorption
• Retains water iso-osmotically in PT- dilutes luminal fluid which opposes NaCl reabsorption
• Inhibits transport process in the thick AscLH by an unknown mechanism
• Expands extracellular fluid volume- increase GFR and inhibit renin release
• Increase renal blood flow, especially to medulla- medullary hypertonicity is reduced- corticomedullary osmotic gradient dissipated -> passive salt reabsorption is

reduced

• Pulmonary edema
• Heart failure

Contraindicated in

• ATN
• Anuria
• Pulmonary edema
• Acute LVF
• CHF
• Cerebral hemorrhage
• Headache, N, V

• Mannitol is never used for treatment of chronic edema or as a natriuretic
• Increased ICP- cerebral edema
• Increased intraocular pressure
• To maintain GFR and urine flow in impending ARF- prerenal cause
• To counteract low osmolality of plasma/ECF due to rapid hemodialysis or peritoneal dialysis

Glycerol and isosorbide

• Orally- 0.5-1.5 g/kg oral

solution

• Same as mannitol

• IV glucose can cause hemolysis
• Not suitable in

diabetics

• Raised IOP, ICP

Spironolactone

• 25-100

mg/day daily orally

• Spironolactone acts from interstitial side of tubular cells in late DT and CD combines with MR and inhibit formation of Aldosterone induced Proteins in competitive manner; increases Na+ and decreases K+ excretion
• It has no action in absence of aldosterone

• Hyperkalemia
• Acidosis
• Drowsiness, ataxia, mental confusion
• Epigastric distress, loose motion
• Gynecomastia, ED or loss of libido in men
• Breast tenderness, menstrual irregularity

in female

• Conn’s syndrome
• To counteract potassium loss due to thiazide and loop diuretic
• Edema
• Hypertension
• CHF
• Cirrhosis and nephrotic syndrome where there is secondary hyperaldosteronism