Thursday, September 30, 2010

Chlorthalidone.......what a miss!

Chlorthalidone is a diuretic acting on the distal convoluted tubule...same as Hydrochlorthiazide. It is a 'thiazide like diuretic'....as it has a different structure than thiazide diuretics, but acts on the same Na-Cl symporter in the DCT. Chlorthalidone first came to light ..when used in the MRFIT trial in the 1970s. Since then chlorthalidone has been the diuretic of choice in the major hypertension trials - ALLHAT, Hypertension Detection and Follow-up Program (HDFP), Systolic Hypertension in the Elderly Program (SHEP). And chlorthalidone was the only antihypertensive showing some mortality benefit in the ALLHAT trial. 
Inspite of these data, im surprised that we still chose HCTZ on top of chlorthalidone. I cant figure out a valid reason for this swap.(If anyone knows ...let me know)

Studies done to compare Chlorthalidone with HCTZ in the past(1976)..were very small..but they all showed that  chlorthalidone once a day is equally efficacious to HCTZ twice a day....in fact with a trend towards even better blood pressure control and a slightly lesser incidence of hypokalemia. A recent study from Iowa showed a superior antihypertensive effect of chlorthalidone than HCTZ. (again ...small study- 30 pts....short duration-8wks.....no hard outcomes.....but hard to discard!)


So......Chlorthalidone seems to have a definite edge over HCTZ both in reducing BP and in preventing adverse cardiac events..with a similar or may be a better side effect profile.
Why is this difference between the two ? Well...we know the answer to some extent. 
1. Chlorthalidone has a longer elimination half life (50 hrs Vs 10 hrs for HCTZ) -- this means more sustained antihypertensive effects. This has been nicely shown in the above study from Iowa.
2. Bioavailability is the same as HCTZ, but it is 99% protein bound..which helps limit glomerular filtration and excellent delivery to action sites thru secretion. HCTZ is 40% protein bound.
3. Chlorthalidone is 99% bound to RBC carbonic anhydrase ...which forms a reservoir for continued action. 
4.Chlorthalidone is a stronger inhibitor of Carbonic anhydrase than HCTZ.....adding to its diuretic effect.
5. Recently..it has been found that Chlorthalidone decreases platelet aggregation and promotes angiogenesis. 
(Hypertension .July 2010)
6. Finally ..COST . 30 tabs of 50mg Chlorthalidone - $20.00 (12.5 mg starting dose....once a day)
                              100 tabs of 50 mg HCTZ          - $ 16.00 (12.5 starting dose......twice a day)


So..if some one is on HCTZ and doing well...it will be reasonable to leave it. Other wise Im changing to Chlorthalidone. And this is easily the first choice thiazide for me!!
Anyone has an argument?!

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