Diuretics

Question 1

Classification

Answer 1

1. Acting at PCT : carbonic anhydrase inhibitor: Acetazolamide.
2. Acting at ascending limb of loop of henle : loop diuretics : Furosemide, torsemide
3. Acting at early distal tubule:
   Thiazides- cholorothiazide, hydrochlorothiazide, bezthiazide.
   Thiazide related diuretics: Chlorthalidone, metolazone, xipamide.
4. Acting at late distal tubule and collecting tubule :
   Aldosterone antagonists- spironolactone.
   Direct inhibitors of renal epithelial sodium channels : amiloride, triamterene.
5. Acting on entire nephron :
   Osmotic diuretics: mannitol, isosorbide, glycerol.

Question 2

Carbonic anhydrase inhibitors
MOA
Therapeutic uses

Answer 2

MOA: Acetazolamide, by inhibiting carbonic anhydrase enzyme, prevents formation of H ions thus Na-H exchange is prevented. Na is excreted along with HCO3 in urine. In DCT, Ma-K exchange leads to loss of K. Net effect of loss of Na, K, HCO in urine resulting in alkaline urine.

Uses:

1. Glaucoma: decreased IOP
2. To alkalinize urine in acidic drug poisoning.
3. Acute mountain sickness. Both symptomatic and prophylactic.
4. Misc- adjuvant in epilepsy, familial periodic paralysis.

Contraindications

1. Liver disease
2. COPD

Question 3

Osmotic diuretics : mannitol

MOA

Answer 3

Moa: mannitol > increases osmolarity of plasma> shift of luid from ICC to ECF > expansion pf ECF volume > increases GFR and mannitolis freely filtered at glmoerulus > increases osmolarity of tubular fluid > Inhibits reabsorption of water , decreases passive absorption of nacl. Net effect: increase in urinary volume, increased urinary excretion of Na, K, Ca, Mg, Cl, HCO, PO

Question 4

Osmotic diuretics
Therapeutic uses
Adverse effects
Contraindications

Answer 4

Uses:

1. To reduce elevated intracranial tension following head injury or tumour.
2. To reduces elevated IOP in acute congestive glaucoma.
3. To prevent acute renal shutdown in shock, cvs surgery, haemolytic transfusion reactions.
4. To maintain osmolarity of ECF after dialysis.

Adverse effects:

1. Can cause marked expansion of ECF leading to pulmonary oedema.
2. Headache, nausea, vomiting.
3. Hyperglycaemia in glycerol.

Contraindicated in : CCF and pulmonary oedema

Question 5

Loop diuretics/ High ceiling Diuretics

MOA

Therapeutic uses

Answer 5

Moa: loop diuretics bind to luminal side if Na-K-2Cl cotransporter and block its function.
There is increased excretion of Na and Cl in urine. Hence more Na reaching DCT is exhanged with K and there is loss of K ions.
Loop diuretics also increase excretion of Ca and Mg.

Uses:

1. During initial stages of renal and cardiac oedema. Useful in hepatic oedema.
2. Iv furosemide with isotonic saline, used in hypercalcaemia as it promotes excretion of Ca in urine.
3. Acute pulmonary oedema : increased pg synthesis and release: increased systemic venous capacitence: shift of blood from central pulmonary to systemic vessels.
4. Mannitol used in cerebral oedema.
5. Hypertension: hypertension associated with CCF/ renal failure and in hypertensive emergencies.
6. To prevent volume overload.

Question 6

Loop diuretics

Adverse effects

Answer 6

1. Electrolytic disturbances
   a. Hypokalaemia- fatigue, muscular weakness, cardiac arrthymias.
   b. Hyponatremia
   c. Hypocalcaemia, hypomagnesaemia
2. a. Hyperglycaemia
   b. Hyperuricaemia
   c. Hyperlipidaemia
3. Ototoxicity
4. Hypersensitivity

Question 7

Loop diuretics

Drug interactions

Answer 7

1. Furosemide + digoxin = digoxin toxicity
2. Furosemide + aminoglycosides = enchance ototoxicity.
3. Furosemide + NSAIDs = Na and H2o retention, diminished anti hypertensive effect of loop diuretics.
4. Furosemide + lithium = hyponatreamia causes compensatory increase in reabsorption of sodium and lithium causing lithium toxicity.
5. Furosemide + amiloride = improves diuretic response- synergistic effect.

Question 8

Thiazides
MOA
USES

Answer 8

Moa - thiazides inhibit Na-Cl symport and increases Na-Cl excretion. Due to increased delivery of Na to late distal tubule, there is increased exchange of Na-K which causes K loss. Net loss of Na, K, Cl, HCO3, in urine.

Uses :

1. Hypertension
2. Oedema
3. Hypercalciuria
4. Diabetes insipidus

Question 9

Thiazides

Adverse effects

Answer 9

1. Hyponatraemia, hypokalaemia, hypomagnesaemia, hypercalcaemia.
2. Hyperglycaemia, hyperlipidaemia, hyperuricaemia.
3. Impotency
4. Skin rashes, photosensitivity, GI disturbances.

Question 10

Spironolactone
K sparing diuretics

MOA
USES

Answer 10

Moa- competitively blocks mineralocortocoid receptor and prevents formation of aldosterone induced proteins. Thus, promotes Na excretion, and K retention. Increases Ca excretion.

Uses:

1. In oedematous conditions associated with secondary hyperaldosteronism.
2. CCF
3. Used with loop diuretics
4. Resistant hypertension due to primary hyperaldosteronism.

Question 11

Amiloride
Direct acting drugs
Uses

Answer 11

1. Treatment of lithium induced nephrogenic diabetes indipidus.
2. Improves mucociliary clearance in patients with cystic fibrosis.