A detailed information about the diuretics - classification of drugs, mechanism of action, side effects, dosage and indications. Classification based on the efficacy of the diuretics. 1. High 2. Moderate 3. Weak A brief introduction given about the nephron structure and its indications.

1. Diuretics
By
Dr. Dinesh Kumar G
Pharm. D

3. CLASSIFICATION
1. High efficacy diuretics (Inhibitors of Na+- K+-2Cl¯ cotransport)
Furosemide, Bumetanide, Torasemide, azosemide, ethacrynic acid
2. Medium efficacy diuretics (Inhibitors of Na+-Cl¯ symport)
I. Benzothiadiazines (thiazides): Chlorothiazide, Hydrochlorothiazide,
Benzthiazide, polythiazide, Hydroflumethiazide, Bendroflumethiazide
II. Thiazide like (related heterocyclics): Chlorthalidone, Metolazone, Xipamide,
Indapamide, Clopamide
3. Weak or adjunctive diuretics
I. Carbonic anhydrase inhibitors – Acetazolamide, methazolamide, dorzolamide.
II. Potassium sparing diuretics
a) Aldosterone antagonist: Spironolactone, Eplerenone
b) Inhibitors of renal epithelial Na+ channel: Triamterene, Amiloride.
III.Osmotic diuretics: Mannitol, Isosorbide, Glycerol

4. HIGH CEILING (LOOP) DIURETICS
(Inhibitors of Na+-K+-2Cl¯ Cotransport)
Furosemide: (Prototype drug)
Rapidly acting highly efficacious oral diuretic - maximal natriuretic effect
Diuretic response - increase with increasing dose - up to 10 L of urine/day.
It is active even in patients with relatively severe renal failure.
The major site of action is the thick AscLH where furosemide inhibits
Na+- K+-2Cl¯ cotransport.
The corticomedullary osmotic gradient is abolished and positive as well as
negative free water clearance is blocked. K+ excretion is increased mainly
due to high Na+ load reaching DT. However, K+ loss is less than that with
thiazides.
Duration: 3 – 6 hours
Onset of Action
IV 2 – 5 min
IM 10 – 20 min
Oral 20 – 40 min

6. • Weak CAse inhibitory action; increases HCO3 ¯ excretion as well
• The diuretic action is independent of acid-base balance of the body and mild
alkalosis occurs at high doses.
• In addition to its prominent tubular action, furosemide causes acute changes in
renal and systemic hemodynamics.
• After 5 min of i.v. injection, renal blood flow is transiently increased and there is
redistribution of blood flow from outer to midcortical zone; g.f.r. generally
remains unaltered despite increased renal blood flow.

7. Dose
Usually 20–80 mg once daily in the morning. In renal insufficiency, up to 200 mg 6
hourly has been given by i.m/i.v route.
In pulmonary edema 40–80 mg may be given i.v.
LASIX 40 mg tab., 20 mg/2 ml inj. LASIX HIGH DOSE 500
mg tab, 250 mg/25 ml inj; (solution degrades spontaneously on exposure to light),
SALINEX 40 mg tab, FRUSENEX 40, 100 mg tab

8. Use of high ceiling diuretics
1. Edema
2. Acute pulmonary edema (acute LVF, following MI)
3. Cerebral edema
4. Hypertension
5. Hypercalcaemia of malignancy
6. Along with blood transfusion in severe anaemia, to prevent volume overload.
7. Infused with hypertonic saline, it may be helpful in hyponatraemia.

9. THIAZIDE AND RELATED DIURETICS
(Inhibitors of Na+-Cl¯ symport)
Thiazides Reach distal tubule
Bind to and block
Na+Cl- cotransport
system
Increases excretion
of Na+ and Cl-
Other effects
• Also inhibit carbonic anhydrase and bicarbonate loss
• Reduces excretion of calcium and uric acid
• Increases the excretion of magnesium and potassium
Duration: 6 - 48 hours
Onset of Action – within 60 mins

11. Uses
1. Edema
2. Hypertension
3. Diabetes insipidus
4. Hypercalciuria
Drug
Daily dose
(mg)
Duration of
action (hr)
Hydrochlorothiazide 12.5–100 6–12
Chlorthalidone 50–100 48
Metolazone 5–20 12–24
Indapamide 2.5–5 12–24
Clopamide 10–60 12–18

12. THIAZIDE AND LOOP DIURETICS
DRUG NAME chlorothiazide, hydrochlorothiazide, indapamide furosemide, bumetanide, ethacrynic acid, torsemide
CLASS Thiazide and thiazide-like diuretics Loop diuretics
MECHANISM
OF ACTION
Inhibit sodium-chloride channels in the distal
convoluted tubules → prevent the reabsorption of
sodium and chloride → salt and water excretion
Inhibit Na-K-2Cl transporter in the thick ascending limb
of loop of Henle → excretion of sodium, potassium, and
chloride → water excretion
INDICATIONS Hypertension, Pulmonary edema, Heart failure, Edema caused by renal and hepatic diseases
ROA PO, IV PO, IV, IM
SIDE
EFFECTS
•Hypercalcemia, uricemia, cholesterolemia, glycemia
•Hypomagnesemia, chloremia, natremia, kalemia
•Metabolic alkalosis
•Increased LDL
•Hypomagnesemia, chloremia, natremia,kalemia
•Metabolic alkalosis
•Hypotension
•Hyperglycemia
CONTRA -
INDICATIONS
AND
CAUTIONS
•Gout
•Diabetes mellitus
•Hyperlipidemia
•Renal failure with anuria
•Existing electrolyte imbalance
•Renal failure with anuria
•Hepatic encephalopathy
•Diabetes mellitus
CLIENT
EDUCATION
Include foods containing potassium in diet; e.g., bananas, potatoes.
Blood pressure self-monitoring and routine laboratory tests needed during therapy
Report symptoms of hypokalemia; e.g., muscle cramps, heart palpitations, ototoxicity; e.g., ringing in the ears
(tinnitus), dizziness, decreased hearing

13. CARBONIC ANHYDRASE INHIBITORS
Carbonic anhydrase (CAse) is an enzyme which catalyzes the reversible
reaction H2O + CO2 ⇌ H2CO3. Carbonic anhydrase thus functions in
CO2 and HCO3 ¯ transport and in H+ ion secretion. The enzyme is
present in renal tubular cell (especially PT) gastric mucosa, exocrine
pancreas, ciliary body of eye, brain and RBC. In these tissues a gross
excess of CAse is present, more than 99% inhibition is required to
produce effects.

14. Acetazolamide
A sulfonamide derivative is a carbonic anhydrase
inhibitor and enhances the excretion of sodium,
potassium and bicarbonate and water. The loss of
bicarbonate leads to metabolic acidosis.
The enzyme is present in renal tubular cell(especially
PT) gastric mucosa, exocrine pancreas, ciliary body
of eye, brain and RBC.
Acetazolamide
Binds to and inhibits
enzyme carbonic anhydrase
Blocks NaHCO3
-
Increased excretion of Na+,
K+, HCO3
- and water
Dose: 250 mg OD–BD
Duration: 8 - 12 hours
Onset of Action – within 90 mins

15. The extrarenal actions of acetazolamide are:
(i) Lowering of intraocular tension due to decreased formation of aqueous
humor (aqueous is rich in HCO¯3).
(ii) Decreased gastric HCl and pancreatic NaHCO3 secretion: This action
requires very high doses—not significant at clinically used doses.
(iii) Raised level of CO2 in brain and lowering of pH →sedation and
elevation of seizure threshold.
(iv) Alteration of CO2 transport in lungs and tissues. These actions are
masked by compensatory mechanisms.

16. Uses
Because of self-limiting action, production of acidosis and hypokalemia,
acetazolamide is not used as diuretic. Its current clinical uses are:
1. Glaucoma: as adjuvant to other ocular hypotensive
2. To alkalinize 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: for symptomatic relief as well as prophylaxis.
Benefit occurs probably due to reduced CSF formation as well as lowering
of CSF and brain pH.
5. Periodic paralysis.

17. Osmotic Diuretics – Mannitol
Mannitol
Filtered freely by glomerulus and Increases
osmolarity of tubular fluid and plasma osmolarity
Shifts fluid from ICF to ECF and increases ECF
volume and Increases urine formation
Water retained in PCT and descending limb of
Henle’s loop
Increased water diuresis
Dose: 1 – 2 g/kg IV infusion

20. DIURETICS: OSMOTIC AND CARBONIC ANHYDRASE INHIBITORS
DRUG NAME mannitol
acetazolamide, dichlorphenamide,
methazolamide, brinzolamide,
dorzolamide
CLASS Osmotic diuretics Carbonic anhydrase inhibitors
MECHANISM
OF ACTION
Freely filtered into the tubules →
increases osmolality of the tubular fluid
→ draws water into the tubules for
excretion along with mannitol
Inhibit carbonic anhydrase enzyme in the
renal tubules → decrease absorption of
bicarbonate and sodium → diuresis
•Inhibit carbonic anhydrase enzyme in the
eyes → decrease production of the aqueous
humor → decrease intraocular pressure
INDICATIONS
•Glaucoma
•Increased intracranial pressure
•Induce renal excretion of toxic
substances (myoglobin from
rhabdomyolysis, hemoglobin from
hemolysis)
•Adjuncts to other diuretics for edematous
conditions (e.g., heart failure, pulmonary
edema)
•Cystinuria
•Gout
•Open-angle glaucoma
ROA IV PO, IV, Opth

21. SIDE EFFECTS
•Exacerbation of fluid overload
conditions
•Dehydration
•Hypotension
•Confusion
•Nausea
•Vomiting
•Metabolic acidosis
•Hypokalemia
•Hyperchloremia
•Neurological side effects, e.g., headache,
seizures, mental status changes, paraesthesia
•Gastrointestinal side effects, e.g., altered
sense of taste, nausea, vomiting and diarrhea
•Side effects with IV forms: hepatic
necrosis, agranulocytosis, aplastic anemia
CONTRA -
INDICATIONS AND
CAUTIONS
•Renal failure with anuria
•Fluid overload conditions
(e.g., heart failure, pulmonary
edema)
•Dehydration
•Severe renal or hepatic disease (e.g.,
cirrhosis)
•Electrolyte abnormalities (e.g.,
hyponatremia, hyperkalemia)
•Respiratory acidosis
•Chronic obstructive pulmonary disease
•Sulfa allergy

22. ASSESSMENT
AND
MONITORING
Baseline assessment
Patent IV, indwelling urinary catheter, ICP monitor
•Vital signs, lung sounds, SpO2, weight, BUN, creatinine,
electrolytes, serum mOsm, urinalysis, urine out 30–50
mL/hr; neurological status
•Check the mannitol solution crystals; warm solution to
dissolve; use an in-line filter
Monitoring
Vital signs, lung sounds, SpO2, electrolytes, BUN, creatinine,
I & O
•Signs of fluid overload; signs of hypovolemia and
hypotension
•Notify the health care provider for serum sodium more than
150 mEq/L or serum osmolality more than 320 mOsm
•Signs of IV site infiltration
•Therapeutic response: decreased ICP, improved level of
consciousness, increased urine output
•Rebound increased ICP
•Patient IV site
•Baseline assessment: blood gas
analysis, CBC, platelets,
glucose, BUN, creatinine, liver
function tests
•Monitor CBC, platelets, blood
gas analysis; glucose for
diabetic clients
•Therapeutic response:
decreased edema, normal acid-
base balance
CLIENT
EDUCATION
•Purpose of medication
•Report trouble breathing, headache, blurred vision, or pain at the IV site

23. 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.
Spironolactone
Binds aldosterone receptor
Inhibits action of aldosterone
Increases sodium and water excretion, and
decreases potassium excretion

25. Use
1. To counteract K+ loss due to thiazide and loop diuretics.
2. Edema: It is more useful in cirrhotic and nephrotic edema in which
aldosterone levels are generally high. Spironolactone is frequently added
to a thiazide/loop diuretic in the treatment of ascites due to cirrhosis of
liver. It breaks the resistance to thiazide diuretics that develops due to
secondary hyperaldosteronism and reestablishes the response.
3. Hypertension: Used as adjuvant to thiazide to prevent hypokalaemia, it
may slightly add to their
antihypertensive action
4. CHF
Dose: 25–50 mg BD–QID; max 400 mg/day

26. POTASSIUM SPARING DIURETICS
Amiloride
Amiloride
Bind to sodium channels on DCT and CD
Increases sodium excretion and retain potassium
Dose: 5 – 10 mg OD - BD
T1/2 – 20 hours

28. POTASSIUM-SPARING DIURETICS
DRUG NAME spironolactone, eplerenone amiloride, triamterene
CLASS Potassium-sparing diuretics
MECHANISM OF
ACTION
Block aldosterone receptors → decrease the synthesis of
epithelial sodium channels (ENaC) and hydrogen pumps
→ increase sodium excretion, and decrease potassium
and hydrogen excretion
Block ENaC → increase sodium excretion,
while preserving potassium
INDICATIONS
•Hypertension
•Pulmonary edema
•Heart failure
•Edema caused by renal and hepatic diseases
•Hyperaldosteronism (spironolactone)
ROA PO
SIDE EFFECTS
•Hyperkalemia
•Metabolic acidosis
•Gynecomastia
•Impotence
•Hyperkalemia
•Metabolic acidosis
•Kidney stones
CONTRAINDICATIO
NS AND CAUTIONS
•Hyperkalemia
•Renal failure with anuria
•Severe liver diseases
CLIENT EDUCATION
•Avoid high-potassium foods and salt substitutes
Report
Nausea, vomiting, muscle twitching or cramps, trouble breathing, heart palpitations
•Endocrine problems; e.g., menstrual irregularities, gynecomastia, impotence

29. Thank You