Thiazides Mechanism Of Action *ANIMATED* HD

THIAZIDES ARE THE MOST WIDELY USED CLASS OF DIURETICS. THIAZIDES ARE CALLED THAT BECAUSE THEY CONTAIN SULFURE AND ARE SULFONAMIDE DERVIATIVES, THEY ARE KNOWN TO BE MODERATELY POTENT DIURETICS. THIAZIDES ARE MAINLY USED IN HYPERTENSION TREATMENT, THEY'RE EITHER USED ALONE OR IN COMBINATION WITH ACE INHIBITORS. THEY'RE USED IN HYPERCALCIURIA AS THEY REDUCE CALCIUM IONS EXCRETION BENEFITING PATIENTS WITH CALCIUM OXALATE STONES IN THE URINARY TRACT. HOW DO THEY WORK? THIAZIDES REDUCE WATER REABSORPTION IN THE NEPHRON BY INHIBITING THE SODIUM CHLORIDE SYMPORTER IN THE DISTAL CONVOLUTED TUBULE, NORMALLY SODIUM AND CHLORIDE ENTER THE DISTAL CONVOLUTED TUBULE CELL THROUGH THE SYMPORTER THEN THEY GET REABSORBED BACK INTO THE BLOOD STREAM THROUGH SODIUM POTASSIUM ATPASE CHANNEL AND CHLRIDE CHANNEL, THIAZIDES BLOCK THIS SYMPORTER CAUSEING THE SODIUM AND SUBSEQUENTLY WATER TO GET FILTERED INTO THE URINE. ALTHOUGH THE DIURETIC EFFECT OF THIAZIDES IS WEAK, THIAZIDES CAUSE VASODIALATION THAT HELPS REDUSING BLOOD PRESSURE AS WELL, UNFORTUNATLY THE MECHANISM OF THE VASODIALATION IS YET TO BE UNDERSTOOD. CHLOROTHIAZIDE IS THE FIRST ORALLY AVAILABLE THIAZIDE DIURETICS, HOWEVER RECENTLY, NEW THIAZIDE LIKE DIURETICS HAVE BEEN INTRODUCED LIKE CHLORTHALIDONE WHICH IS A NONTHIAZIDE THAT BEHAVES PHARMACOLOGICALLY LIKE HYDROCHLOROTHIAZIDE WIHT AN ADVANTAGE OF LONG DURATION OF ACTION, METOLAZONE IS ANOTHER THIAZIDE LIKE DRUG THAT IS MORE POTENT AND UNLIKE THIZAIDES CAUSES SODIUM EXCRETION IN ADVANCED RENAL FAILURE. THE MOST SIDE EFFECTS OF THIAZIDES ARE CAUSED BY ELECTROLYTE DEPLETION RESULTING FROM PROLONGED USE, LIKE HYPOKALEMIA, HYPOCLOREMIA, HYPONATERMIA AND DEHYDRATION. SINCE THIAZIDE IS NOT METABILISED AND EXCRETED UNCHANGED IN THE URINE, THEY CANNOT BE GIVEN IN PATIENTS WITH RENAL DISEASE. THIAZIDES ARE CONTRAINDICATED WITH DIGOXIN, AS A RESULT OF HYPOKALEMIA THE DRUG INTERATION CAN RESULT IN CARDIAC ARRYTHMIA, FURTHUREMORE, THIAZIDES ARE CONTRAINDICATED WITH DRUGS THAT CAUSE FLUID RETENTION SUCH AS CORTICOSTEROIDS AND NSAIDS.