Hydrochlorothiazide; Uses, Dosage, Side Effects, Interactions









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Hydrochlorothiazide is a thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It is used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism.

Hydrochlorothiazide is a diuretic medication often used to treat high blood pressure and swelling due to fluid build up.It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It has been used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. Other uses include diabetes insipidus, renal tubular acidosis, and to decrease the risk of kidney stones in those with high calcium level in the urine.

Mechanism of Action of Hydrochlorothiazide

Hydrochlorothiazide, a thiazide diuretic, inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, hydrochlorothiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.

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The exact mechanism of the diuretic effect of hydrochlorothiazide is not fully understood. Bioelectric studies suggested a direct inhibition of sodium ion reabsorption in the toad bladder and studies of the effects of hydrochlorothiazide on ion movement in the isolated rabbit distal colon suggested specific inhibition of chloride absorption. In micropuncture studies, chloride transport in the medullary collecting duct of the rat kidney was almost completely inhibited by hydrochlorothiazide. To examine the effect of hydrochlorothiazide on Na+ -K+ ATPase activity in seven separate segments along the nephron of spontaneously hypertensive rats and the normotensive control rats. Hydrochlorothiazide was administered at 15 mg/kg for 7 days by an osmotic minipump. Individual nephron segments then were dissected from the kidney and ouabain-sensitive Na+ -K+ ATPase activity was determined. Activity in the normotensive strain was decreased by hydrochlorothiazide administration in the distal convoluted tubule and was increased in the cortical collecting duct. Hydrochlorothiazide decreased Na+ -K+ ATPase activity in all but the proximal straight tubule and medullary collecting duct in the spontaneously hypertensive strain.

Indications of Hydrochlorothiazide

  • High blood pressure
  • Edema
  • Nephrocalcinosis
  • Osteoporosis
  • Diabetes insipidus
  • Acidosis, renal tubular
  • Calcium nephrolithiasis
  • Premenstrual tension with edema
  • Prophylaxis of preeclampsia
  • A patient with hypercalciuria was treated with hydrochlorothiazide, 100 mg/day. On the 3rd day the urinary calcium dropped from a
  • Hydrochlorothiazide has been evaluated for use in lessening sodium and water retention in conditions of preeclampsia during pregnancy.
  • Although prophylactic use of hydrochlorothiazide apparently does not prevent preeclampsia, some benefit may be derived when hydrochlorothiazide is administered during the second trimester to pregnant women with underlying hypertension.
  • Indicated in the management of hypertension, and as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Is also useful in edema due to various forms of renal dysfunction such as nephrotic syndrome.
  • Thiazide diuretics are also used for prevention of calcium-containing renal stones.

Contra-Indications of Hydrochlorothiazide

  • Sympathectomy
  • Diabetes
  • Increased activity of the parathyroid gland
  • High cholesterol
  • Gout
  • Low amount of magnesium in the blood
  • The high amount of calcium in the blood
  • Low amount of sodium in the blood
  • Extreme Loss of body water
  • Low amount of potassium in the blood
  • Liver failure
  • Acute inflammation of the pancreas
  • Systemic lupus erythematosus
  • Yellowing of the skin in a newborn child
  • The high amount of uric acid in the blood
  • Azotemia
  • High blood sugar
  • secondary angle-closure glaucoma
  • Decreased blood volume
  • Absence of urine formation
  • Acid-Base problem with low chloride and basic pH blood

Dosages of Hydrochlorothiazide

  • Strengths: 25 mg; 50 mg; 100 mg; 50 mg/5 mL; 12.5 mg

Edema

  • Usual dose: 25 mg to 100 mg orally once or twice daily.

Hypertension

  • Initial dose: 25 mg orally once daily
  • Maintenance dose: May increase to 50 mg orally daily, as a single or 2 divided doses

Nephrocalcinosis

  • Initial: 25 mg orally once daily
  • Maintenance dose: May increase to 50 mg twice daily

The pediatric dose for edema

  • Less than 6 months: Up to 3 mg/kg/day (up to 1.5 mg/pound) orally in 2 divided doses
  • Less than 2 years: 1 to 2 mg/kg/day (0.5 to 1 mg/pound) orally daily as a single dose or in 2 divided doses
  • Maximum dose 37.5 mg per day
  • 2 to 12 years: 1 to 2 mg/kg/day (0.5 to 1 mg/pound) orally daily as a single dose or in 2 divided doses
  • Maximum dose 100 mg per day

Side Effects of Hydrochlorothiazide

Most common

More common

Less common

Drug Interactions of Hydrochlorothiazide

Pregnancy & Lactation of Hydrochlorothiazide

FDA Pregnancy Category B

Pregnancy

This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.

Lactation

This medication passes into breast milk. If you are a breastfeeding mother and are taking hydrochlorothiazide, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

References

 

Hydrochlorothiazide

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