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Hydrochlorothiazide; Uses, Dosage, Side Effects, Interactions

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.

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.

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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

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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

dry mouth,
Increase the feeling of thurst
increase the frequency of urination
Abdominal or stomach discomfort
low blood pressure,
difficult, burning, or painful urination
increased potassium blood levels (hyperkalemia),
low blood sugar (hypoglycemia), and
diarrhea
symptoms of weakness, muscle pain (myalgia)
abdominal pain (GI complaints), lactic acidosis (rare)
low blood levels of vitamin B-12
nausea,vomiting
chest discomfort
chills, dizziness
bloating/abdominal distention
constipation
heartburn

More common

chest pain;
Abdominal or stomach discomfort
cough or hoarseness
decreased appetite
diarrhea
fast or shallow breathing
trouble breathing; or
dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, confusion, chest pain, shortness of breath, uneven heartbeats, seizure)
lower back or side pain
muscle pain or cramping
painful or difficult urination

Less common

dry mouth
feeling of thirst
drowsiness
restlessness
muscle cramp
fast or abnormal heartbeat
severe nausea or vomiting
tiredness
weakness
dry hair and skin
increased feelings of being cold
pain when you eat or drink
severe nausea or vomiting

Drug Interactions of Hydrochlorothiazide

anticholinergic medications (e.g., oxybutinin)
barbiturates (e.g., phenobarbital)
calcium supplements
cholestyramine
colestipol
corticosteroids (e.g., prednisone) and ACTH
medications that lower blood pressure
medications that reduce potassium levels (e.g., other diuretics such as furosemide)
narcotics (e.g., codeine, oxycodone, morphine)
nonsteroidal anti-inflammatory medications (NSAIDs; e.g., ibuprofen, indomethacin,naproxen)
oral diabetes medications (e.g., glyburide, gliclazide, metformin, pioglitazone)
pseudoephedrine
quinidine
rituximab
tetracyclines (e.g., tetracycline, minoclycline, doxycycline)
topiramate
warfarin

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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.