Brands, Medical Use, Clinical Data
- Diuretics, Thiazide
- Antihypertensive Agents
Brands / Synonyms
Aldoclor; Aldoril; Alurene; Chloriazid; Chlorosal; Chlorothiazid; Chlorothiazide; Chlorthiazide; Chlortiazid; Chlorurit; Chlotride; Chlrosal; Clotride; CT; Diupres; Diuresal; Diuril; Diuril Boluses; Diuril I.V.; Diuril Lyovac [As Sodium Salt]; Diurilix; Diurite; Diutrid; Esidrix; Flumen; Hydro-D; Hydrochlorothiazide; Hydrochlorothiazide Intensol; Hydrodiuril; Lyovac Diuril [As Sodium Salt]; Microzide; Minzil; Neo-Dema; Oretic; Salisan; Salunil; Saluretil; Saluric; Sk-Chlorothiazide; Thiazide; Urinex; Warduzide; Yadalan; Zide
Chlorothiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. It is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension.
Like other thiazides, chlorothiazide promotes water loss from the body (diuretics). It inhibits 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. Chlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic efficacy. Chlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate.
Mechanism of Action
As a diuretic, chlorothiazide 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 chlorothiazide 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 chlorothiazide 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.
Oral, rat LD50: > 10 g/kg. Signs of overdose include 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.
Biotrnasformation / Drug Metabolism
Chlorothiazide is not metabolized but is eliminated rapidly by the kidney.
Hypersensitivity to this or other sulfonamide-derived drugs.
When given concurrently the following drugs may interact with thiazide diuretics.
- Alcohol, barbiturates, or narcotics: Potentiation of otthostatic 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: Cholestytamine and colestipol resins have the potential of binding thiazide diuretics and reducing diuretic absorption from the gastrointestinal tract.
- 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 chlorothiazide.
- 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 chlorothiazide 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.
- Drug/Laboratory Test Interactions: Thiazides should be discontinued before carrying out tests for parathyroid function.