Brands, Medical Use, Clinical Data
Drug Category
- Diuretics
- Antihypertensive Agents
Dosage Forms
Brands / Synonyms
Acuretic; Aldactazide; Aldoril; Amturnide; Apresazide; Aquarills; Aquarius; Atacand HCT; Avalide; Benicar HCT; Bisoprolol and Hydrochlorothiazide; Bremil; Caplaril; Capozide; Captopril and Hydrochlorothiazide; Chlorosulthiadil; Chlorothiazide; Chlorsulfonamidodihydrobenzothiadiazine Dioxide; Chlorzide; Cidrex; Dichlorosal; Dichlorotride; Dichlotiazid; Dichlotride; Diclotride; Dicyclotride; Dihydrochlorothiazid; Dihydrochlorothiazide; Dihydrochlorothiazidum; Dihydrochlorurit; Dihydrochlorurite; Dihydroxychlorothiazidum; Diovan HCT; Direma; Disalunil; Diu-Melusin; Diuril; Drenol; Dutoprol; Dyazide; Enalapril and Hydrochlorothiazide; Esidrex; Esidrix; Esimil; Exforge HCT; Fluvin; Fosinopril and Hydrochlorothiazide; HCTZ; HCZ; Hidril; Hidrochlortiazid; Hidroronol; Hidrotiazida; Hydralazine and Hydrochlorothiazide; Hydril; Hydro-Aquil; Hydro-D; Hydro-Diuril; Hydrochlorothiazid; Hydrochlorothiazide; Hydrochlorothiazide Intensol; Hydrochlorthiazide; Hydrodiuretic; Hydrodiuril; Hydropres; Hydrosaluric; Hydrothide; Hydrozide; Hypothiazid; Hypothiazide; Hyzaar; Idrotiazide; Inderide; Ivaugan; Jen-Diril; Lisinopril and Hydrochlorothiazide; Lopressor HCT; Lotensin HCT; Maschitt; Maxzide; Megadiuril; Methyldopa and Hydrochlorothiazide; Metoprolol and Hydrochlorothiazide; Micardis HCT; Microzide; Moduretic; Monopril-HCT; Nefrix; Neo-Codema; Neoflumen; Newtolide; Oretic; Palonyl; Panurin; Perovex; Primogyn; Prinzide; Quinapril and Hydrochlorothiazide; Quinaretic; Ro-Hydrazide; SER-AP-ES; Servithiazid; Spironolactone and Hydrochlorothiazide; Tekturna HCT; Telmisartan and Hydrochlorothiazide; Teveten HCT; Thiaretic; Thiuretic; Thlaretic; Timolide; Triamterene and Hydrochlorothiazide; Tribenzor; Unipres; Uniretic; Urodiazin; Vaseretic; Vetidrex; Zestoretic; Ziac; Zide
Indications
For the treatment of high blood pressure and management of edema.
Pharmacology
Thiazides such as hydrochlorothiazide promote water loss from the body (diuretics). They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.
Mechanism of Action
As a diuretic, hydrochlorothiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like hydrochlorothiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of hydrochlorothiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.
Absorption
50-60%
Toxicity
The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. The oral LD50 of hydrochlorothiazide is greater than 10 g/kg in the mouse and rat.
Biotrnasformation / Drug Metabolism
Hydrochlorothiazide is not metabolized.
Contraindications
Anuria.
Hypersensitivity to this product or to other sulfonamide-derived drugs.
Drug Interactions
When given concurrently the following drugs may interact with thiazide diuretics.
Alcohol, barbiturates, or narcotics: potentiation of orthostatic hypotension may occur.
Antidiabetic drugs: (oral agents and insulin) - dosage adjustment of the antidiabetic drug may be
required.
Other antihypertensive drugs: additive effect or potentiation.
Cholestyramine and colestipol resins: Absorption of hydrochlorothiazide is impaired in the presence of
anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide
and reduce its absorption from the gastrointestinal tract by up to 85 and 43 percent, respectively.
Corticosteroids, ACTH: intensified electrolyte depletion, particularly hypokalemia.
Pressor amines (e.g., norepinephrine): possible decreased response to pressor amines but not
sufficient to preclude their use.
Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine): possible increased responsiveness
to the muscle relaxant.
Lithium: generally should not be given with diuretics. Diuretic agents reduce the renal clearance of
lithium and add a high risk of lithium toxicity. Refer to the package insert for lithium preparations before use of
such preparations with Hydrochlorothiazide.
Non-steroidal Anti-inflammatory Drugs: In some patients, the administration of a non-steroidal
anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop,
potassium-sparing and thiazide diuretics. Therefore, when Hydrochlorothiazide and non-steroidal anti-inflammatory
agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the
diuretic is obtained.
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