Thiazide Diuretics

We have to review anatomy and physiology of the kidneys to understand these diuretics better.  In the picture below, find the glomerulus, the proximal tubule, distal tubule, nephron loop and the collecting duct.

The filtration takes place in the glomerulus.  Electrolytes, fluids and any solutes get filtered by the nephron to get rid of wastes. There’s plenty of reabsorption that takes place during this process.

If you’re taking a drug that’s supposed to be a great diuretic, what’s it going to do to reabsorption? A diuretic is going to decrease/block reabsorption so the water is excreted into the bladder.

Where is your largest pressure gradient difference? The bottom, at the nephron loop (of Henle) has the greatest pressure gradient, so that’s where most of the reabsorption is taking place. So if you want to create your most powerful diuretic, you would want it to work at the loop of Henle.

So we have high ceiling loop, thiazide and potassium sparing diuretics…

The high ceiling loop diuretics are the most powerful because they tend to work in the nephron loop somewhere around the ascending loop near the distal tubule.

The thiazides work closer to the distal tubule and have less affect on absorption because its impact is higher up in the nephron.

Can we use a high ceiling loop and thiazide together? Not really because the loop diuretic will do a lot of work and the thiazide won’t do much.  However, the thiazide metolazone (Zaroxolyn) will be an exception and can be used with a loop diuretic because it’s the only thiazide diuretic that has a DUAL mechanism of action that blocks reabsorption in both the distal tubule and proximal tubule. When used together with the high ceiling loop diuretic, the diuresis effect is not additive, but synergistic.  It will have a super powerful diuretic effect that is going to be utilized only by cardiac and nephrology experts.

The potassium sparing diuretics work up in the collecting duct. Would these be very good diuretics? No, because it has very little impact on reabsorption. Therefore, it won’t create powerful diuresis.

Back to Thiazide’s…

Thiazide diuretics block reabsorption of sodium and water in the distal tubule of kidney, so it’s a mild to moderate diuretic.

But remember metolazone works also on the proximal tubule so it becomes synergistic with the high ceiling loop diuretics.

Thiazides increase secretion of potassium in urine so blood potassium levels drop so they can become hypokalemic.

Other Metabolic Effects

  1. Increases blood uric acid, sugar, cholesterol and triglyceride levels. These are all problems in diabetics and cardiac patients. Ironically, what group of patients would normally be prescribed diuretics? Diabetics and cardiac patients. For this reason we are using very low doses and we’re still getting the benefit so it’s not as bad as it sounds.
  2. Increase blood calcium levels. So if a person has a high blood calcium levels already (like a bone disease), this is not a good choice.
  3. Decreases blood potassium and magnesium.

Use of Thiazide Diuretics

  • Primarily for hypertension.
  • Management of edema (metolazone with or without a loop diuretic)


We don’t use it with a person with hypercalcemia because it increases blood calcium levels.

Thiazide Diuretic List

Hint: One has the word thiazide in it, but the others do not.

  • Hydrochlorthiazide (Hydrodiuril) – p.o.
  • Metolazone (Zaroxolyn) – p.o.
  • Chlorthalidone (Hygroton)