Chlotride - General Information
A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p812)
Pharmacology of Chlotride
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. Chlotride affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic efficacy. Chlotride increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate. After oral doses, 10-15 percent of the dose is excreted unchanged in the urine. Chlotride crosses the placental but not the blood-brain barrier and is excreted in breast milk.
Chlotride for patients
For treatment of high blood pressure, you must take chlorothiazide regularly for it to be effective. As blood pressure declines gradually, it can take several weeks before you experience the full benefit of chlorothiazide, and you must continue taking it even if you are feeling well. Note that chlorothiazide does not cure high blood pressure, it simply keeps it under control.
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.
Hypersensitivity to this or other sulfonamide-derived drugs.
Additional information about Chlotride
Chlotride Indication: Chlotride 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.
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.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Chlorothiazide
Synonyms: Chlorothiazid; Chlorthiazide; Chlortiazid
Drug Category: Diuretics, Thiazide; Antihypertensive Agents
Drug Type: Small Molecule; Approved
Absorption: Rapidly absorbed following oral administration.
Toxicity (Overdose): 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.
Protein Binding: Approximately 40% bound to plasma proteins.
Biotransformation: Chlorothiazide is not metabolized but is eliminated rapidly by the kidney.
Half Life: 45-120 minutes
Dosage Forms of Chlotride: Suspension Oral
Chemical IUPAC Name: 6-chloro-1,1-dioxo-4H-benzo[e][1,2,4]thiadiazine-7-sulfonamide
Chemical Formula: C7H6ClN3O4S2
Chlorothiazide on Wikipedia: https://en.wikipedia.org/wiki/Chlorothiazide
Organisms Affected: Humans and other mammals