Talk:Chlortalidone

Chlorthalidone vs. Chlortalidone

There seems to be some question over Chlorthalidone vs. Chlortalidone. The gent who forwarded Chlorthalidone to Chlortalidone indicated that the former was the spelling used in the UK until it was changed to the latter. My research seems to indicate something different. According to the Novartis web site, Chlorthalidone is a Thiazide-based diuretic (that is NOT marketed in the UK according to Novartis #1) and Chlortalidone appears to be a Sulfonamide-based diuretic marketed by Sandoz. Perhaps the spelling was changed in the UK because of the product difference between Novartis and Sandoz. I don't know so I have written to both manufacturers requesting clarification of the terms and usages. I will update these articles when I have more information: Hygroton, Chlorthalidone, and Chlortalidone. JimScott 01:46, 16 January 2007 (UTC)

Chlortalidone and chlorthalidone are, in fact, one and the same. Chlorthalidone was the British Approved Name (i.e., the name used in the UK) until 2004, when it was changed to the International Nonproprietary Name chlortalidone. (see this link) Unfortunately, to make matters worse, chlorthalidone is still the United States Adopted Name (i.e., the name used in the U.S.) According to Wikipedia's convention on naming of drug pages, articles should be named according to the INN whenever possible, hence the move to chlortalidone. Feel free to expand the article though, it's still only a tiny stub. Fvasconcellos 02:06, 16 January 2007 (UTC)

mortality

My read of the ALLHAT trial is that chlorthalidone is equal to amlodapine and lisinopril in mortality/morbidity, both all cause and cardiovascular; chlorthalidone was only superior in controlling BP. (Contrary to the text)129.176.151.10 (talk) —Preceding undated comment added 12:22, 2 July 2010 (UTC).

The actual published results would seem to support the current text. Here are the results and conclusion from the JAMA article's abstract:

Results Mean follow-up was 4.9 years. The primary outcome occurred in 2956 participants, with no difference between treatments. Compared with chlorthalidone (6-year rate, 11.5%), the relative risks (RRs) were 0.98 (95% CI, 0.90-1.07) for amlodipine (6-year rate, 11.3%) and 0.99 (95% CI, 0.91-1.08) for lisinopril (6-year rate, 11.4%). Likewise, all-cause mortality did not differ between groups. Five-year systolic blood pressures were significantly higher in the amlodipine (0.8 mm Hg, P = .03) and lisinopril (2 mm Hg, P<.001) groups compared with chlorthalidone, and 5-year diastolic blood pressure was significantly lower with amlodipine (0.8 mm Hg, P<.001). For amlodipine vs chlorthalidone, secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine (10.2% vs 7.7%; RR, 1.38; 95% CI, 1.25-1.52). For lisinopril vs chlorthalidone, lisinopril had higher 6-year rates of combined CVD (33.3% vs 30.9%; RR, 1.10; 95% CI, 1.05-1.16); stroke (6.3% vs 5.6%; RR, 1.15; 95% CI, 1.02-1.30); and HF (8.7% vs 7.7%; RR, 1.19; 95% CI, 1.07-1.31).

Conclusion Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive. They should be preferred for first-step antihypertensive therapy.

Sbelknap (talk) 18:35, 24 September 2018 (UTC)

lay language

I reverted an edit that removed much of the lay language in the first sentence of the lede.Sbelknap (talk) 19:03, 31 October 2018 (UTC)

Also, made initial part of lede entirely lay language. Sbelknap (talk) 19:54, 31 October 2018 (UTC)

pharmacokinetics

We need to add a pharmacokinetics section, as the longer half-life of chlortalidone is highly relevant to its superior efficacy compared to HCTZ. I will put together a draft over the next few days. Sbelknap (talk) 19:13, 31 October 2018 (UTC)

Side effects

Ref is clear but is an unreliable source. For some reason, this source is used widely on wikipedia. Unclear why

"Chlortalidone has a higher risk of side effects than hydrochlorothiazide."

Quote = However, chlorthalidone use is more frequently associated with adverse metabolic effects, particularly hypokalemia and hyponatremia, compared with HCTZ.

Doc James (talk · contribs · email) 09:34, 2 November 2019 (UTC)

Agreed. That ref is clear. However, it is also wrong and inconsistent with the body of the article. This error in the lede has been corrected at least once before. Here's the relevant text in the main article:

Chlortalidone has a modestly greater effect on blood pressure than hydrochlorothiazide but the two medications have similar effects on lowering potassium. The thiazide-like diuretics (chlortalidone and indapamide) are more effective than the thiazide-type diuretics (including hydrochlorothiazide) for reducing the risk of heart attack, stroke, and heart failure in persons with high blood pressure and the thiazide-like and thiazide-type diuretics have similar rates of adverse effects.

Sbelknap (talk) 15:42, 2 November 2019 (UTC)

Okay so refs come to different conclusions, adjusted. Doc James (talk · contribs · email) 22:43, 4 November 2019 (UTC)

The opinion piece by Maria Czarina Acelajado provides no evidence supporting the assertion that chlortalidone is more likely to cause adverse effects than hydrochlorothiazide. The statement to this effect in Acelajado does not reference any evidence but instead gives a naked assertion. In contrast, the meta-analyses provide detailed evidence and analysis on this. Sbelknap (talk) 23:05, 4 November 2019 (UTC)

It is a review not an opinion piece.[1] Doc James (talk · contribs · email) 08:38, 10 November 2019 (UTC)

Here is another [2] Doc James (talk · contribs · email) 08:49, 10 November 2019 (UTC)

References

This Liang W, Ma H, Cao L, Yan W, Yang J (November 2017). "Comparison of thiazide-like diuretics versus thiazide-type diuretics: a meta-analysis". J. Cell. Mol. Med. 21 (11): 2634–2642. doi:10.1111/jcmm.13205. PMC 5661252. PMID 28631393.

Quote = "In conclusion, using thiazide-like diuretics is superior to thiazide-type diuretics in reducing blood pressure without increasing the incidence of hypokalemia, hyponatraemia and any change of blood glucose and serum total cholesterol."

Compares thiazide liek diuretics to thiazide type. Not chlortalidone specifically. Doc James (talk · contribs · email) 08:46, 13 November 2019 (UTC)

This is a direct quote from the article: "Twelve trials were identified: five based on the comparison of indapamide versus hydrochlorothiazide and seven based on the chlorthalidone versus hydrochlorothiazide." Sbelknap (talk) 04:47, 14 November 2019 (UTC)

Text

In this edit "hypertriglyceridemia" and "low blood sodium" were added as common side effects.

I checked both references and do not see it mention. User:Sbelknap please explain what happened. Doc James (talk · contribs · email) 22:43, 4 November 2019 (UTC)

Liang et al concludes risk of low blood sodium (hyponatremia) as being the same in thiazide diureticss vs thiazide-like diuretics : "Meanwhile, in the analysis of side effects, the incidence of hypokalemia ([95% CI]; 1.58 [0.80, 3.12]; P = 0.19), hyponatremia ([95% CI]; −0.14 [−0.57, 0.30], P = 0.54), change of blood glucose ([95% CI];0.13 [−0.16, 0.41], P = 0.39) and total cholesterol ([95% CI]; 0.13 [−0.16, 0.41], P = 0.39) showed that there is no statistical significant differences between the two groups of drugs."

It is the triglyceride component of cholesterol that increases with exposure to thiazides. Liang mentions TG (triglycerides) in the methods section. "The changes of blood pressure, serum TG and glucose were computed as the difference in the BP values at the final follow‐up (or specific time‐point if multiple time‐points were provided) compared to the baseline or initial measurement." Also, the 4 articles that Liang cites regarding cholesterol provide more information. For example, Pareek et al addresses this.

Sbelknap (talk) 23:41, 4 November 2019 (UTC)

User:Sbelknap Where does it say these are "common side effects"? Doc James (talk · contribs · email) 08:32, 10 November 2019 (UTC)

The book written by Peri and cited in the main article has a chapter on drug-induced hyponatremia. This chapter cites Singh et al's article which states, "The rate of thiazide-induced hyponatremia is about 30%, with this being most common in the first 3 months of exposure to thiazide."

Regarding the frequency of thiazide-induced hyponatremia compared with other drug-induced causes, the article by Ware et al has this sentence in the introduction: "Severe TIH (serum sodium <125 mM) causes debilitating symptoms (5) and is the most common form of drug-induced hyponatremia requiring hospital admission." Sbelknap (talk) 19:51, 11 November 2019 (UTC)

This is not a review https://www.ncbi.nlm.nih.gov/pubmed/22840676

Doc James (talk · contribs · email) 08:48, 13 November 2019 (UTC)

Please re-read my comment. The book by Peri is a review. I cite the particular article here for your info. There is no question that hyponatremia is common adverse effect of exposure to chlorthalidone. Sbelknap (talk) 04:52, 14 November 2019 (UTC)

References

Only some recommend over HCTZ

And now that some do not we need to attribute this.

Hripcsak, George; Suchard, Marc A.; Shea, Steven; Chen, RuiJun; You, Seng Chan; Pratt, Nicole; Madigan, David; Krumholz, Harlan M.; Ryan, Patrick B.; Schuemie, Martijn J. (17 February 2020). "Comparison of Cardiovascular and Safety Outcomes of Chlorthalidone vs Hydrochlorothiazide to Treat Hypertension". JAMA Internal Medicine. doi:10.1001/jamainternmed.2019.7454.

Doc James (talk · contribs · email) 20:19, 19 February 2020 (UTC)

We have a summary of this trial by the ACC here[3]. I am sure we will hear more soon as this gets combined into position statements and reviews. Doc James (talk · contribs · email) 20:25, 19 February 2020 (UTC)

The best available evidence is the meta-analysis of the nine clinical trials that directly compared chlortalidone and hydrochlorothiazide, so I've added that to the adverse effect section. Sbelknap (talk) 22:52, 24 March 2020 (UTC)

Not a great study

• [4]

Is small. Not listed as a review. And is from 2000. Doc James (talk · contribs · email) 23:44, 25 March 2020 (UTC)

Okay for the body of the text. Doc James (talk · contribs · email) 23:45, 25 March 2020 (UTC)

Magnesium

Ref says "Thiazide-like diuretics have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia." not seeing the 20% Doc James (talk · contribs · email) 20:00, 28 March 2020 (UTC)