chlorthalidone (Hygroton)
Jump to navigation
Jump to search
Introduction
Tradename: Hygroton.
Indications
- hypertension
- 12.5-50 mg QD
- doses > 50 mg/day do not increase anti-hypertensive effects
- not effective in patients with creatinine clearance < 30 mL/min
- useful in patients with stage 4 chronic renal failure eGFR 15-20 mL/min[8]
- not associated with cardiovascular benefits when compared with HCTZ[7][9]
- use of chlorthalidone vs HCTZ associated with lower cardiovascular morbidity & mortality after myocardial infarction or ischemic stroke[10]
- not more renal protective than HCTZ in patients with HTN[11] ef) may lower risk of hip fracture in elderly (RR=0.79)[6]
- edema
- prevention of calcium stones[5]
- nephrogenic diabetes insipidus
Dosage
Tabs: 25 mg.
Dosage adjustment in renal failure
- QOD dosing if creatinine clearance < 10 mL/min
Pharmacokinetics
- bioavailability varies with different dosage forms
- 90% bound mostly to erythrocytes
- onset of action 2 hours
- 1/2life 54 hours
- duration of action: 24-72 hours
- 30-60% of drug is excreted unchanged in the urine
elimination via kidney
1/2life = 56 hours
protein binding = 90 %
Adverse effects
- hyperuricemia
- rash
- increased low-density lipoprotein (LDL)
- hypokalemia (1-10%)
- hypochloremic alkalosis
- dilutional hyponatremia
- electrolyte abnormalities (hypokalemia, hyponatremia) are more common with chlorthalidone than hydrochlorothiazide[4][7]
- hyperglycemia
- glucosuria
- orthostatic hypotension
- GI complaints
- photosensitivity
- pancreatitis
- vasculitis
- hypercalcemia (rare)
- blood dyscrasia (rare)
- prerenal azotemia
- drug adverse effects of renin-angiotensin-aldosterone system inhibitors (RAAS inhibitors)
- drug adverse effects of thiazide diuretics
- drug adverse effects of sulfonamides
- drug adverse effects of diuretics
- drug adverse effects of antihypertensive agents
Drug interactions
- may enhance hypokalemic effects of agents that lower serum K+ levels: i.e. beta-2 adrenergic agonists
- may decrease lithium clearance
- may increase requirements for oral hypoglycemic agents &/or insulin
- probenecid
- may increase the risk of NSAID-induced renal failure
- drug interaction(s) anticonvulsants with anti-bacterial agents
- drug interaction(s) SGLT2 inhibitors (flozins) with diuretics
- drug interaction(s) of diuretics in combination with Zn+2
- drug interaction(s) of antiarrhythmic agents in combination with diuretics
- drug interaction(s) of beta-2 adrenergic receptor agonists with thiazide diuretics
- drug interaction(s) of calcium channel blockers with diuretics
- drug interaction(s) of renin-angiotensin-aldosterone inhibitors with trimethoprim-sulfamethoxazole
- drug interaction(s) of antibiotics with warfarin
- drug interaction(s) of benzodiazepines with thiazide diuretics
- drug interaction(s) of lithium carbonate with thiazide diuretics
- drug interaction(s) of diuretics with angiotensin II receptor antagonists
- drug interaction(s) of diuretics with ACE inhibitors
- drug interaction(s) of NSAIDs, diuretics & angiotensin II receptor antagonists
- drug interaction(s) of NSAIDs, diuretics & ACE inhibitors
- drug interaction(s) of NSAIDs & antihypertensives
Mechanism of action
- enhances secretion of Na+, Cl- & H2O by interfering with Na+ & Cl- transport across the renal tubular epithelium mediated by SLC12A3
- site of action: distal tubule
- thiazides also effect the excretion of other electrolytes including K+ & HCO3-
- thiazides inhibit tubular excretion of Ca+2
More general terms
Component of
- chlorthalidone/reserpine
- azilsartan/chlorthalidone (Edarbyclor, Takeda)
- chlorthalidone/clonidine (Combipres)
- atenolol/chlorthalidone (Tenoretic)
References
- ↑ Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 123
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Jump up to: 4.0 4.1 Dhalla IA et al Chlorthalidone Versus Hydrochlorothiazide for the Treatment of Hypertension in Older Adults: A Population-Based Cohort Study. Ann Intern Med. 19 March 2013;158(6):447-455 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23552325 <Internet> http://annals.org/article.aspx?articleid=1667266
- ↑ Jump up to: 5.0 5.1 Deprecated Reference
- ↑ Jump up to: 6.0 6.1 Puttnam R, Davis BR, Pressel SL Association of 3 Different Antihypertensive Medications With Hip and Pelvic Fracture Risk in Older Adults. Secondary Analysis of a Randomized Clinical Trial. JAMA Intern Med. Published online November 21, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27893045 <Internet> http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2587085
Colon-Emeric CS, Lee R Cardiovascular Medications and Fractures. Dodging Complexity. JAMA Intern Med. Published online November 21, 2016. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27893011 <Internet> http://annals.org/aim/article/2588175/targeting-functional-decline-alzheimer-disease-randomized-trial - ↑ Jump up to: 7.0 7.1 7.2 Hripcsak G, Suchard MA, Shea S et al Comparison of Cardiovascular and Safety Outcomes of Chlorthalidone vs Hydrochlorothiazide to Treat Hypertension. JAMA Intern Med. Published online February 17, 2020. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32065600 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2760777
- ↑ Jump up to: 8.0 8.1 Agarwal R, Sinha AD, Cramer AE et al. Chlorthalidone for hypertension in advanced chronic kidney disease. N Engl J Med 2021 Nov 5; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34739197 https://www.nejm.org/doi/10.1056/NEJMoa2110730
- ↑ Jump up to: 9.0 9.1 Ishani A, Cushman WC, Leatherman SM et al Chlorthalidone vs. Hydrochlorothiazide for Hypertension - Cardiovascular Events. N Engl J Med 2022. Dec 14 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26760416 https://www.nejm.org/doi/10.1056/NEJMoa2212270
- ↑ Jump up to: 10.0 10.1 Ishani A, Hau C, Cushman WC, Leatherman SM et al Chlorthalidone vs Hydrochlorothiazide for Hypertension Treatment After Myocardial Infarction or Stroke: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024 May 1;7(5):e2411081. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38743423 PMCID: PMC11094558 Free PMC article. Clinical Trial.
- ↑ Jump up to: 11.0 11.1 Ishani A, Hau C, Raju S et al Chlorthalidone vs Hydrochlorothiazide and Kidney Outcomes in Patients With Hypertension: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024 Dec 2;7(12):e2449576. PMID: https://www.ncbi.nlm.nih.gov/pubmed/39656458 Free PMC article. Clinical Trial.