Thiazide and thiazide-like diuretics

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Thiazide and thiazide-like diuretics

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USMLE® Step 2 style questions USMLE

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A 62-year-old man comes to the office because of severe left flank pain for the past week. The pain has an intermittent squeezing quality, radiates to the groin, and is associated with nausea and vomiting. The patient does not have abdominal pain or fever.  Temperature is 36.8 C (98.2 F), pulse is 90/min, respirations are 17/min, and blood pressure is 130/78 mmHg. Physical examination shows severe left-sided costovertebral angle tenderness and urine dipstick reveals microscopic hematuria. Urinalysis shows crystals in the shape of an envelope. The patient is started on a medication that decreases urinary calcium excretion. Which of the following segments of the nephron is affected by this medication? 

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Diabetes insipidus p. 349

thiazides for p. 627

Heart failure p. 316

thiazides for p. 627

Hypercalcemia p. 609

thiazides as cause p. 627

Hypercalciuria

thiazides for p. 627

Hyperglycemia

thiazides p. 627

Hyperlipidemia p. 307

thiazides p. 627

Hypertension p. 304

thiazides for p. 627

Hyperuricemia

thiazides p. 627

Hyponatremia p. 609

thiazides p. 627

Metabolic alkalosis p. 604, 610

thiazides p. 627

Osteoporosis p. 467

thiazides for p. 627

Thiazide diuretics

heart failure p. 316

hypertension p. 320

Thiazides p. 627

gout p. 249

site of action p. 625

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Diuretics are medications that act on the kidneys to increase production of urine, therefore elimination of water from the body.

There are 5 main types of diuretics - carbonic anhydrase inhibitors, osmotic diuretics, loop diuretics, potassium sparing diuretics, and last but not least, thiazide and thiazide-like diuretics - which we’ll get intimately acquainted with during this video.

Now, the basic unit of the kidney is called a nephron, and each nephron is made up of a glomerulus, which filters the blood. The filtered content goes through the renal tubule, where excess waste and molecules, such as ions and water, are removed or filtered through an exchange between the tubule and the peritubular capillaries.

So the renal tubule plays a huge role in secretion and reabsorption of fluid and ions - such as sodium, potassium, and chloride, in order to maintain homeostasis - or the balance of fluid and ions in our body.

The renal tubule has a few segments of its own: the proximal convoluted tubule; the U-shaped loop of Henle, with a thin descending, a thin ascending, and a thick ascending limb; and finally, the distal convoluted tubule, which empties into the collecting duct, which collects the urine.

Alright, so thiazide and thiazide-like diuretics are taken perorally, and once in the blood, they travel to the kidneys where they are secreted by the proximal convoluted tubule into the lumen of the renal tubule.

An important point to make here is that they are secreted by the same secretory system that secretes uric acid into the tubule, so they compete with the secretion of uric acid, therefore increasing uric acid levels in the blood.

Next, they travel along with the filtrate until they reach the distal convoluted tubule. This part of the nephron is lined by epithelial cells.

Now, on the luminal side of these cells, there’s a nifty little sodium-chloride transporter. This channel reabsorbs one sodium and one chloride ion together from the tubule, into the cell. Sodium is reabsorbed along with water into the interstitium, and then into the bloodstream.

Summary

Thiazide and thiazide-like diuretics are a class of medications used to treat hypertension and edema by promoting the elimination of salt and water from the body. Thiazide diuretics work by inhibiting reabsorption, specifically by blocking the sodium-chloride symporter in the distal convoluted tubule in the kidney. This in turn leads to increased excretion of sodium and water.

The most commonly used thiazides are chlorothiazide and hydrochlorothiazide; and the most commonly used thiazide-like diuretics are metolazone, indapamide, and chlorthalidone. Thiazide and thiazide-like diuretics are generally considered safe and effective drugs for treating high blood pressure and edema. However, they can cause some side effects such as electrolyte imbalances, dehydration, increased blood sugar levels, and increased uric acid levels.

Sources

  1. "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
  2. "Rang and Dale's Pharmacology" Elsevier (2019)
  3. "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
  4. "Comparison of thiazide-like diuretics versus thiazide-type diuretics: a meta-analysis" Journal of Cellular and Molecular Medicine (2017)
  5. "Clinical and Molecular Features of Thiazide-Induced Hyponatremia" Current Hypertension Reports (2018)