Diuretics

• Diuretics (natriuretics) are drugs which cause a

net loss of Na+ and water in urine
• 1. High efficacy diuretics
(Inhibitors of Na+K+-2Cl¯ cotransport)
Sulphamoyl derivatives
Furosemide,
Bumetanide,
Torasemide
2. Medium efficacy diuretics (Inhibitors of Na+-
Cl¯ symport)
• (a) Benzothiadiazines (thiazides)
Hydrochlorothiazide, Benzthiazide,
Hydroflumethiazide, Bendroflumethiazide
• (b) Thiazide like (related heterocyclics)
Chlorthalidone, Metolazone, Xipamide,
Indapamide, Clopamide
• 3. Weak or adjunctive diuretics
(a) Carbonic anhydrase inhibitors Acetazolamide
(b) Potassium sparing diuretics
(i) Aldosterone antagonist: Spironolactone,
Eplerenone
(ii) Inhibitors of renal epithelial Na+ channel:
Triamterene, Amiloride.
(c) Osmotic diuretics Mannitol, Isosorbide, Glycerol
HIGH CEILING (LOOP) DIURETICS (Inhibitors of
Na+-K+-2Cl¯ Cotransport)
• Furosemide (Frusemide)
• The major site of action is the thick AscLH
(therefore called loop diuretics) where
furosemide inhibits Na+- K+-2Cl¯ cotransport
• Furosemide has weak CAse inhibitory action
• It increases HCO3¯ excretion
• Furosemide increases Ca2+ excretion as well as
Mg2+ excretion
• It tends to raise blood uric acid level
 Use of high ceiling diuretics
• 1. Edema
• 2. Acute pulmonary edema (acute LVF,
following MI)
• 3. Cerebral edema
• 4. Hypertension
• 5. Along with blood transfusion in severe
anaemia, to prevent volume overload
• 6. Hypercalcaemia of malignancy
THIAZIDE AND RELATED DIURETICS
MOA:
These are Inhibitors of Na+-Cl¯ symport
urinary K+ excretion is increased in parallel to
the natriuretic response
 Adverse effects
• Hypokalaemia
• Acute saline depletion
• Dilutional hyponatremia
• GIT and CNS disturbances
• Hearing loss
• Allergic manifestations
• Hypocalcaemia
 Uses
• 1. Edema
• 2. Hypertension
• 3. Diabetes insipidus
• 4. Hypercalciuria
 CARBONIC ANHYDRASE INHIBITORS

• Acetazolamide
• It is a sulfonamide derivative which
noncompetitively but reversibly inhibits CAse
(type II) in PT cells resulting in slowing of
hydration of CO2 ,decreased availability of H+
to exchange with luminal Na+ through the
Na+-H+ antiporter
 Uses
• 1. Glaucoma: as adjuvant to other ocular
hypotensives
• . 2. To alkalinise urine: for urinary tract
infection or to promote excretion of certain
acidic drugs.
• 3. Epilepsy: as adjuvant in absence seizures
when primary drugs are not fully effective
• 4. Acute mountain sickness
• 5. Periodic paralysis
• Adverse effects are frequent.
• Acidosis, hypokalaemia, drowsiness, paresthesias,
fatigue, abdominal discomfort.
• Hypersensitivity reactions—fever, rashes. Bone
marrow depression is rare but serious.
• It is contraindicated in liver disease: may
precipitate hepatic coma by interfering with
urinary elimination of NH3 (due to alkaline urine).
Acidosis is more likely to occur in patients of COPD.
 POTASSIUM SPARING DIURETICS

• Aldosterone antagonists and renal epithelial

Na+ channel inhibitors indirectly conserve K+
while inducing mild natriuresis, and are called
‘potassium sparing diuretics’
• Spironolactone It is a steroid, chemically related to the
mineralocorticoid aldosterone.
• Aldosterone penetrates the late DT and CD cells and acts by
combining with an intracellular mineralocorticoid receptor (MR)
,induces the formation of ‘aldosterone-induced proteins’ (AIPs).
• The AIPs promote Na+ reabsorption and K+ secretion.
Spironolactone acts from the interstitial side of the tubular cell,
combines with MR and inhibits the formation of AIPs in a
competitive manner.
• It has no effect on Na+ and K+ transport in the absence of
aldosterone, while under normal circumstances, it increases Na+
and decreases K+ excretion.
 Uses
• 1. To counteract K+ loss due to thiazide and
loop diuretics.
• 2. Edema
• 3. Hypertension
• 3. CHF
 Adverse effects

• The side effects are drowsiness, ataxia, mental

confusion, epigastric distress and loose

motions. Spironolactone interacts with

progestin and androgen receptors as well

 Cont…..
• . In addition, it may enhance testosterone
clearance or its peripheral conversion to estradiol,
producing dose and duration of treatment related
hormonal side effects like gynaecomastia, erectile
dysfunction or loss of libido in men, and breast
tenderness or menstrual irregularities in women
 OSMOTIC DIURETICS
• Mannitol
• 1. Retains water iso osmotically in PT—dilutes
luminal fluid which opposes NaCl
reabsorption.
• 2. Inhibits transport processes in the thick
AscLH by an unknown mechanism.
Quantitatively this appears to be the largest
contributor to the diuresis
• 3. Expands extracellular fluid volume (because
it does not enter cells, mannitol draws water
from the intracellular compartment)—
increases g.f.r. and inhibits renin release.
• Uses Mannitol

• It is never used for the treatment of chronic

edema or as a natriuretic. Its indications are:
1. Increased intracranial or intraocular tension
(acute congestive glaucoma, head injury, stroke,
• 2. To maintain g.f.r. and urine flow in
impending acute renal failure, e.g. in shock,
severe trauma, cardiac surgery
• 3. To counteract low osmolality of
plasma/e.c.f. due to rapid haemodialysis or
peritoneal dialysis (dialysis disequilibrium).