CHLORTHALIDONE

Chlortalidone  or chlorthalidone (USAN) is a diuretic drug used to treat hypertension, originally marketed as Hygroton in the USA. It is described as a thiazide diuretic (or, rather, a thiazide-like diuretic because it acts similarly to the thiazides but does not contain the benzothiadiazine molecular structure). Compared with other medications of the thiazide class, chlortalidone has the longest duration of action but a similar diuretic effect at maximal therapeutic doses. It is often used in the management of hypertension and edema.
Unlike loop diuretics, chlortalidone efficacy is diminished in patients with certain renal diseases (e.g. chronic renal disease). A clinical trial  in 2002 compared chlortalidone to doxazosin in the treatment of high-risk hypertensive patients. In this study, only chlortalidone significantly reduced the risk of combined cardiovascular disease events, especially heart failure, when compared with drugs such as doxazosin. Chlortalidone was approved by the FDA in 1960. The ALLHAT study conclusions showed that there was no significant difference in all-cause mortality, fatal heart disease, or non-fatal myocardial infarction when chlortalidone was compared with lisinopril or amlodipine but did show decrease rates of heart failure after 6 years when compared with amlodipine and decreased rates of cerebrovascular disease after 6 years when compared with lisinopril leading the study conclusions to say that thiazide-type diuretics are preferred first-step in antihypertensive therapy.

(RS)-2-chloro-5-(1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)benzene-1-sulfonamide

Mechanism of action

Chlortalidone increases the excretion of sodium, chloride, and water into the renal lumen by inhibiting sodium ion transport across the renal tubular epithelium. Its primary site of action is in the cortical diluting segment of the ascending limb of the loop of Henle. Thiazides and related compounds also decrease the glomerular filtration rate, which further reduces the drug's efficacy in patients with renal impairment (e.g. renal insufficiency). By increasing the delivery of sodium to the distal renal tubule, chlortalidone indirectly increases potassium excretion via the sodium-potassium exchange mechanism (i.e. apical ROMK/Na channels coupled with basolateral NKATPases). This can result in hypokalemia and hypochloremia as well as a mild metabolic alkalosis; however, the diuretic efficacy of chlortalidone is not affected by the acid-base balance of the patient being treated.
Initially, diuretics lower blood pressure by decreasing cardiac output and reducing plasma and extracellular fluid volume. Eventually, cardiac output returns to normal, and plasma and extracellular fluid volume return to slightly less than normal, but a reduction in peripheral vascular resistance is maintained, thus resulting in an overall lower blood pressure. The reduction in intravascular volume induces an elevation in plasma renin activity and aldosterone secretion, further contributing to the potassium loss associated with thiazide diuretic therapy.

Other use
Chlorthalidone may also be used to treat patients with diabetes insipidus and certain electrolyte disturbances and to prevent kidney stones in patients with high levels of calcium in their blood. Talk to your doctor about the possible risks of using this medicine for your condition.


Before taking chlorthalidone,
tell your doctor and pharmacist if you are allergic to chlorthalidone, sulfa drugs, or any other drugs.
tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially other medicines for high blood pressure, anti-inflammatory medications such as ibuprofen (Motrin, Nuprin) or naproxen (Aleve), corticosteroids (e.g., prednisone), lithium (Eskalith, Lithobid), medications for diabetes, probenecid (Benemid), and vitamins. If you also are taking cholestyramine or colestipol, take it at least 1 hour after chlorthalidone.
tell your doctor if you have or have ever had diabetes, gout, or kidney, liver, thyroid, or parathyroid disease.
tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking chlorthalidone, call your doctor immediately.
if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking chlorthalidone.
you should know that this drug may make you drowsy. Do not drive a car or operate machinery until you know how this drug affects you.
remember that alcohol can add to the drowsiness caused by this drug.
plan to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen. Chlorthalidone may make your skin sensitive to sunlight.


Usual Adult Dose for Edema
Initial dose: 50-100 mg orally once a day.
Maintenance dose: 25-100 mg once a day or
50-200 mg every other day.

Usual Adult Dose for Hypertension
Initial dose: 25 mg orally once a day (15 mg for Thalitone).
Maintenance dose: 25-100 mg once a day (15-50 mg for Thalitone).

Renal Dose Adjustments
Chlorthalidone is not expected to be filtered into the renal tubule (its site of action) when the glomerular filtration rate is less than 10 mL/min.

Dose Adjustments
Dosage adjustments are recommended to be made no more frequently than weekly. Patients with liver disease or renal dysfunction should have dosage adjustments made cautiously.