1. DIURETIC DRUGS

2. Introduction Are drugs that induce a state of increased urine flow.
Are inhibitors of renal ion transporters that decrease the reabsorption of Na⁺ at different sites in the nephron such that Na⁺ and other ions enter the urine in greater than normal amounts along with water.

3. Uses of diuretics Disorders involving abnormal fluid retention (edema)
Treatment of hypertension

4. Diuretic classes DRUGS SITE OF ACTION Carbonic anhydrase inhibitors
Loop diuretics
Thiazide diuretics
Potassium sparing diuretics
Osmotic diuretics
SITE OF ACTION
PCT
Ascending LH
DCT
Collecting tubules
All areas in the nephron

5. Diuretics: Sites of Action
Carbonic Anhydrase
Inhibitors
Eg: Acetazolamide
Thiazides
Eg: Chlorothiazide
Na+
Cl-
HCO3-
K+ - Sparing
Eg: spinolactone
Na+
Na+
Cl- K+ K+
Loop Diuretics
Eg: Furosemide

6. CARBONIC ANHYDRASE INHIBITORS
Acetazolamide
Dorzolamide
Methazolamide

8. CARBONIC ANHYDRASE INHIBITORS
ACTION : INHIBITS CARBONIC ANHYDRASE ENZYME
SITE : PCT
EFFECTS : NO H+ FOR REABSORPTION OF Na +
HCO3- EXCRETION INCREASES
CAUSES MILD DIURESIS
↓Na⁺/H⁺ antiport
↑Cl⁻ in the blood---hyperchloremia

9. Causes significant bicarbonate loss causing alkalinization of urine
Hyperchloremic metabolic acidosis
reduction in aqueous humor production

10. THERAPEUTIC USES Chronic treatment of GLAUCOMA ( MC INDICATION )
REDUCES AQUEOUS HUMOR PRODUCTION
DECREASES IOP.
DRUGS USED : ACETAZOLAMIDE,
DORZOLAMIDE.

11. Acute Mountain Sickness
Given nightly for 5 days before the ascent to prevent weakness, breathlessness, dizziness, nausea, cerebral and pulmonary edema

13. OTHER USES -- Metabolic alkalosis
Can decrease production of CSF, therefore used to treat pseudotumor cerebri

14. SIDE EFFECTS BICARBONATURIA HYPOKALEMIA HYPERCHLOREMIA PARESTHESIAS
RENAL STONES (calcium oxalate, struvite stone)
SULFONAMIDE HYPERSENSITIVITY
CI: in hepatic cirrhosis(hepatic encephalopathy)

15. Loop Diuretic Drugs Furosemide Bumetanide Torsemide
Ethacrynic acid --no longer in use because of toxicity.

16. Action
Inhibit the Na/K/Cl transport system in the luminal membrane of the thick ascending limb of Henle.
Reabsorption of Na/K/Cl reduced → their excretion.
Increases Ca²⁺, mg²⁺ excretion
The most efficacious of all the diuretics
They increase the synthesis of prostaglandins, with their diuretic effect enhanced by prostaglandins

18. USES Major uses: --Edematous conditions Acute pulmonary edema
Acute hypercalcemia
Management of edema
HTN by ↓ing peripheral vascular resistance & reduction in blood volume
Hyperkalemia
Renal failure

19. SE Ototoxicity: more with ethacrynic acid Hypokalemia
Metabolic alkalosis
Hyperuricemia
Hypocalcemia
hypomagnesemia
Gout
Dehydration
Cardiac arrhythmias
Sulfonamide hypersensitivity except ethacrynic acid

20. Drug interactions Aminoglycosides: ↑ ototoxicity
↑ Digoxin toxicity due to electrolyte disturbance (hypokalemia)
Chronic administration ↓es lithium clearance

21. THIAZIDES Most commonly used diuretic.
Inhibition of Na⁺/Cl⁻ transporter from the distal convoluted tubule.
↑ing Na⁺ and Cl⁻ excretion → to ↑ diuresis
Enhance calcium reabsorption in the distal convoluted tubule – reduces Ca excretion.
Loss of K

23. Drugs Chlorothiazide Chlorthalidone Hydrochlorothiazide Indapamide
Metalazone
Methyclothiazide
Trichlomethiazide

24. USES
Essential HTN by vasodilatation of peripheral vasculature (K⁺ channel opener)
CHF
Renal failure
Nephrogenic Diabetes Insipidus
Hypercalciuria

25. SE Hypokalemia Metabolic alkalosis Hyperuricemia Hypercalcemia
Cardiac arrhythmias
Hypotension
Hyponatremia
Hyperlipidemia
Hypersensitivity to sulfonamides
Hyperglycemia

26. Drug interactions Increases digoxin toxicity
Contraindicated in diabetics

27. POTASSIUM SPARING DIURETICS
These diuretics inhibit aldosterone receptor at the Collecting tubule and late distal tubule by stimulating Na⁺ excretion and K⁺ retention
ALDOSTERONE:
It increases the reabsorption of sodium and water.
Excretion of potassium in the distal tubules of the kidneys.
Thus increases blood pressure.

28. ENAC: EPITHELIAL SODIUM CHANNELS

29. Drugs
Spironolactone
Amiloride
Triamterene

30. Drugs Spironolactone: inhibits aldosterone at its receptor sites.
Increasing Na and H2O excretion while retaining K

31. USES OF SPIRONOLACTONE
Diuretic: given in conjunction with a thiazide and loop diuretics to prevent K-excretion
Diuretic of choice in patients with hepatic cirrhosis
Secondary hyperaldosteronism
Heart failure to prevent cardiac remodeling

32. SE Hyperkalemia Gynecomastia (spironolactone)
Anti androgen effects (spironolactone)
Menstrual irregularities
GIT disturbance

33. Triamterene and Amiloride
MOA: blocks Na transport channels resulting in a decrease in Na/K exchange not dependent on the presence of aldosterone
Causes retention of K⁺

34. Side effect Leg cramps (Triamterene & Amiloride)
Increased BUN (Triamterene & Amiloride)

35. Osmotic diuretics
Have ability to carry water with them into the tubular fluid, therefore increasing water excretion.
Acts on all parts of the nephron.

36. OSMOTIC DIURETICS MANNITOL/urea Parental (I.V.)
increase water excretion.
Increased tubular fluid osmolarity
Increase urine volume.
Less effect or no effect on Na excretion

37. USES To increase urine volume in anuric conditions
such as toxic ingestion, trauma, drug toxicities.
To decrease intracranial or intraocular pressure.
Acute renal failure

38. SE Dehydration Hypovolemia Hyponatremia Headache Nausea & vomiting
Pulmonary edema: very common with mannitol