DIURETIC AGENTS

DIURETIC – An agent that increases urine volume & sodium

excretion.
NATRIURETIC – An agent that increases renal sodium
excretion.
PERMEABILITY OF VARIOUS SEGMENTS :
SEGMENT PERMEABLE IMPERMEABLE
PCT Na+; Water -----------
DTL Water Na+; Urea
ATL Na+; Urea Water
DCT Na+ Water
CD Na+; Urea Water [ No ADH]
Water [ with ADH]
TRANSPORT PROCESSES IN NEPHRON
RENAL SEGMENTS AND PERMEABILITY :
1. Proximal Convoluted Tubule :
Lumen Interstitium

Na+ Na+
K+
HCO3- + H+ H+ + HCO3- HCO3-
Na+

H2CO3 H2CO 3
CA CA
H2O + CO2 CO2 + H2O
DIURETIC AGENTS :
1. CARBONIC ANHYDRASE INHIBITORS :
ACETAZOLAMIDE, METHAZOLAMIDE
ACTION –
- Inhibition of carbonic anhydrase in PCT leading to increased
Na+ & HCO3- excretion.

EFFECTS ON URINARY EXCRETION –

- Excretion of Na+, HCO3- , K+
CARBONIC ANHYDRASE INHIBITORS :
EFFECT ON OTHER ORGANS :
1. Eye - Aqueous humor
2. RBC - CO2 levels
3. Stomach - acid secretion
4. CNS – Paraesthesia & dizziness
5. Blood vessels – Vasodilatation
SIDE EFFECTS –
1. Allergic reactions, bone marrow depression
2. Renal calculi
3. Worsening of hepatic encephalopathy,Contraindicated in
COPD
4. Dizziness, Paraesthesia
CARBONIC ANHYDRASE INHIBITORS :
THERAPEUTIC USES :
1. Edema
2. Open angle glaucoma – Dorzolamide, Brinzolamide
3. Epilepsy
4. Altitude sickness
5. Familial hypokalemic periodic paralysis
6. Metabolic alkalosis
7. Urinary alkalinization
LOOP OF HENLE :
LUMEN INTERSTITIUM

Na+ Na+ Na+

K+ K+
2Cl-

(+) potential K+ 2Cl-

Mg++, Ca++ Mg++, Ca++

LOOP DIURETICS :
• Also called high ceiling diuretics
CHEMISTRY :
Furosemide & Bumetanide – Sulfonamides
Torsemide – Sulfonylurea
Ethacrynic acid – Phenoxy acetic acid derivative

ACTION :
Site of action – Na+/K+/2Cl- symport in ATL
LOOP DIURETICS :
RENAL EXCRETION :
• Na+, Cl+
• K+
• Ca++, Mg++
• HCO3-
• Uric acid initially
• Uric acid later
• Blockade of concentrating ability during hydropenia
• Blockade of diluting ability during water diuresis
LOOP DIURETICS :
PHARMACOKINETICS :
• Furosemide – Renal metabolism; Low oral bioavailability,
Short t1/2
• Bumetanide &Torsemide – Hepatic metabolism; High
bioavailability, long t1/2 with torsemide
SIDE EFFECTS :
1. Hypotension, circulatory collapse
2. Arrhythmia, Weakness, fatigue, muscle cramps
3. Hypochloremic alkalosis
4. Tetany
LOOP DIURETICS :
SIDE EFFECTS :
5. Ototoxicity
6. Hyperglycemia, hyperuricemia
7. HDL, LDL
DRUG INTERACTIONS :
• Digitalis
• Cisplatin
• Aminoglycosides
• NSAIDs
• Probencid
LOOP DIURETICS :
USES :
1. Edema – CCF, Liver cirrhosis, Nephrotic syndrome, acute
pulmonary edema.
2. Forced diuresis in drug overdose
3. Hypercalcemia – Isotonic saline
4. Life threatening hyponatremia – Hypertonic saline
5. Hypertension
6. Toxicity of bromide, fluoride & iodide
DISTAL CONVOLUTED TUBULE :
LUMEN INTERSTITIUM

Na+ Na+
Cl- K+
PTH
Ca++ Ca++
Na+
Cl-
THIAZIDE DIURETICS :
CHEMISTRY :
•Sulfonamide structure
•Thiazides- Chlorothiazide, Hydrochlorothiazide, Chlorthalidone,
Polythiazide.
•Thiazide like – Indepamide, Metolazone
ACTION :
Site of action : Na+/Cl- symporter in DCT
• Na+, Cl-
• K+
• HCO3-
• Uric acid initially
THIAZIDE DIURETICS :
ACTION :
• Uric acid later
• Ca++
• Blockade of diluting ability in water diuresis
• No effect on concentrating ability.
SIDE EFFECTS :
1. Hypotension, Circulatory collapse
2. Arrhythmia, Weakness, Fatigue, Cramps
3. Hypochloremic alkalosis
4. Hyperglycemia, Hyperuricemia, Hypercalcemia
5. HDL, LDL, Allergic reactions
THIAZIDE DIURETICS :
INTERACTIONS:
1. Digitalis
2. NSAIDs
3. Probencid
USES :
1. Edema – CCF, Liver cirrhosis, Nephrotic syndrome.
2. Hypertension
3. Calcium nephrolithiasis
4. Osteoporosis
5. Nephrogenic diabetes insipidus
OSMOTIC DIURETICS:
GLYCERINE*, ISOSORBIDE*, MANNITOL#, UREA#
ACTION :
- Site – Loop of henle
ECF, Blood viscosity

Renal blood flow

Medullary blood flow

Removal of NaCl & urea from medullary interstitium

OSMOTIC DIURETICS:
ACTION :

Medullary tonicity

Extraction of water from DTL

Concentration of NaCl in ATL

Extraction of NaCl from ATL

Excretion of NaCl
OSMOTIC DIURETICS:
RENAL EXCRETION :
•Excretion of all electrolytes is increased
•Increased RBF ; GFR unchanged.

SIDE EFFECTS :
1. Hyponatremia, pulmonary edema in CCF pt.
2. Hypernatremia; dehydration
3. Urea – Thrombosis & pain if extravasated; Blood ammonia
4. Mannitol & urea – CI in active cranial bleeding
5. Glycerine - Hyperglycemia
OSMOTIC DIURETICS:
THERAPEUTIC USES :
1. Impending acute renal failure
2. Glaucoma- acute attacks
3. Cerebral edema
4. Dialysis disequilibrium syndrome
COLLECTING TUBULE:
LUMEN INTERSTITIUM
Cl-
Principal cell

+ Aldosterone
Na+
+
K+
Na+
K+
+
H2O AQP ADH

H+
POTTASIUM SPARING DIURETIC :
1. RENAL EPITHELIAL SODIUM CHANNEL
INHIBITORS:
CLASS : Triamterene, Amiloride
ACTION :
Site of action: Epithelial sodium channel in principal cells of late
DCT & CD

• Na+, Cl-
• K+, H+, Mg++, Ca++
• Uric acid
POTTASIUM SPARING DIURETIC :
1. RENAL EPITHELIAL SODIUM CHANNEL
INHIBITORS:
SIDE EFFECTS:
• Hyperkalemia
• Megaloblastic anaemia
• Triamterene- Nausea, Vomiting, Glucose tolerance,
Photosensitivity.
• Amiloride – Nausea, Vomiting, Headache.
THERAPEUTIC USES:
• Combination with other diuretics
• Liddle’s syndrome
• Cystic fibrosis - Li+ induced nephrogenic diabetes insipidus
ALDOSTERONE ANTAGONISTS:
CLASS : Spironolactone, Eplerenone, Canrenone
ACTION :
Site of action – Competitive inhibition of binding of aldosterone
to mineralocorticoid receptor in CD
• Na+, Cl-
• K+, H+, Mg++, Ca++
• Uric acid
SIDE EFFECTS:
•Hyperkalemia
•GIT- Gastritis, Ulcerations, Diarrhea
•Endocrine – Gynecomastia, Impotency, Hirsutism
ALDOSTERONE ANTAGONISTS:
USES:
•Edema & Hypertension in combination with other diuretics
•Primary & secondary aldosteronism
LOOP DIURETICS
1. Site – LOH
2. Short duration of action
3. High ceiling
4. Effective in GFR
5. Hypocalcemia
6. – concentrating &
diluting capacity
THIAZIDES
1. Site - DCT
2. Longer duration
3. Low ceiling
4. Not effective*
5. Hypercalcemia
6. – diluting capacity

*= except metolazone & indepamide