Dr.Rathnakar U P MD.DIH.PGDHMDept of PharmacologyKMC, Mangalore

Introduction

Renal function•Excrete waste product of metabolism,drugs

•Maintain water electrolyte balance

Diuretics:

•Diuretics are the drugs that promote the excretion of Na+ and water from the body by an action on the kidney.

NEPHRON

Classification

DIURETICS• High efficacy diuretics

[Loop diuretics ] (High ceiling diuretics):

• Medium efficacy diuretics

[Thiazide diuretics]

• Weak diuretics1. Potassium sparing diuretics

2. Carbonic anhydrase inhibitors

3. Osmotic diuretics:

• Furosemide, Bumetanide, Torsemide

• Hydrochlorthiazide, Metolazone

• Aldosterone receptor antagonist: Spironolactone, Triamterene, amiloride

• Acetazolamide

• Mannitol, glycerol

MOA• High Efficacy

• Medium Efficacy• Low Efficacy1.Tiamterene,

Amiloride

2.Spironolactone3.CA inhibitors

4.Osmotic

• Inhibition of Na-K-2Cl co-transporter of ascending loop of Henle

• Inhibit Na+-Cl- symport in the DCT

• Inhibit Na+ channel in DT & CT

• Aldosterone antagonist

• Inhibit CA in PT

• Osmotically @ PCT

[Potassium sparing]

Adverse effects: High and Medium Efficacy

• Hypokalaemia• Nausea, vomiting, diarrhoea, Head

ache, Giddiness• Allergic• MetabolicHyperurecemiaHyperglycemiaHypercalcemia[Thiazides]Hypocalcemia[Furosemide]

Uses

High efficacy•Edema: Any causeHeart failure,

Cirrhosis, RenalAcute pulmonary

edemaCerebral edema HTN

Medium efficacy[Thiazides]

•Edema•Hypertension

Potassium Sparing [weak]

Tiamterene & Amiloride

• UsesUsed along with

Thiazides to reduce potassium loss

• Adverse effectsNausea,

Vomiting, diarrhoea

Spironolactone

• UsesEdema-Cirrhosis,

nephroticHeart failure• Adverse effects• Drowsiness,

Hirsutism, Hyperkalemia

CA Inhibitors-Acetazolamide[weak]

• Uses• WeakGlaucomaMountain

sicknessTo alkalinise

urineEpilepsy

• Adverse effectsCommonAcidosis,

hypokalemiaDrowsinessHepatic coma

Osmotic diuretics-Mannitol, Glycerol

• UsesI.VRaise intracranial

tensionAcute glaucomaShould not be

given in Heart failure, pulmonary edema etc.

• Adverse effectsHead acheNauseaVomitingAllergic

reactions

Summary• Diuretics reduce water reabsorption and

increase urine volume • Loop diuretics such as furosemide (frusemide)

inhibit the NaK2Cl cotransporter in the loop of Henle

• Thiazide diuretics inhibit the NaCl cotransporter in the distal tubule

• Amiloride inhibits the epithelial Na channel in the collecting duct

• Spironolactone is an aldosterone antagonist • Mannitol is an osmotic diuretic • Acetazolamide inhibits carbonic anhydrase

inhibitor• Loop diuretics and Thiazide diuretics increase

potassium excretion, • Amiloride and spironolactone reduce

potassium excretion • Used in edema

Antidiuretic hormone (ADH)/Vasopressin

• Synthesized in the hypothalamus

• Secreted from the posterior lobe of pituitary gland

• Rise in plasma osmolarity; contraction of extracellular fluid volume.

• Lypressin• Telipressin• Desmopressin –given

intranasally/orally/im- Diabetes insipidus due to damage to

posterior pituitary- Nocturnal enuresis in patients with

normal pituitary function – intranasal/oral at bed time

Therapeutic uses