chlorthalidone (Rx)

Action and Spectrum

Chlorthalidone inhibits the Na⁺/Cl⁻ symporter in the cortical diluting segment of the ascending limb of the loop of Henle, reducing sodium and chloride reabsorption. This promotes diuresis, decreasing plasma and extracellular fluid volume, which in turn lowers cardiac output and blood pressure. It also increases potassium excretion indirectly and may reduce cardiovascular risk through effects on platelet aggregation, vascular permeability, and angiogenesis, possibly via carbonic anhydrase–related mechanisms. 

Drug Interaction

Adverse Reaction

Adverse drug reactions:   

Frequency Not Defined 

Cardiac dysrhythmia  

Scaling eczema   

Hepatotoxicity  

Systemic lupus erythematosus  

Pulmonary edema  

Stevens-Johnson syndrome   

toxic epidermal necrolysis  

Pancreatitis  

Disorder of hematopoietic structure  

Black Box Warning

Contraindication / Caution

Contraindication 

 Chlorthalidone is contraindicated in patients who are unable to urinate or have a known allergy to chlorthalidone or sulfa drugs. 

Cautions 

Use with caution in individuals with a history of: 

Kidney disease 

Heart failure 

Gout 

Diabetes 

High cholesterol or triglycerides 

Low-salt diets 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy Category: un-assigned 

Breastfeeding warnings:  

The release of the drug into the human breastmilk is known 

Pregnancy Categories:       

Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first trimester or the later trimester.       

Category B: No evidence shown of risk to the fetus found in animal reproduction studies, and there are not enough studies on pregnant women       

Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a result in humans must take care of potential risks in pregnant women       

Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits       

Category X: Drugs listed in this category outweigh risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.       

Category N: There is no data available for the drug under this category 

Pharmacology

Chlorthalidone is a thiazide-like diuretic that inhibits the Na⁺/Cl⁻ symporter in the cortical diluting segment of the ascending limb of the loop of Henle. This action reduces sodium and chloride reabsorption, promoting diuresis and decreasing plasma volume, which lowers blood pressure. It also increases potassium excretion due to enhanced sodium delivery to the distal tubule. Beyond its diuretic effect, chlorthalidone may reduce cardiovascular risk by decreasing platelet aggregation, vascular permeability, and promoting angiogenesis, possibly through carbonic anhydrase–related pathways. 

Pharmacokinetics 

Absorption 

Onset of action begins within 3 hours; peak plasma levels are reached in 2–6 hours. 

Distribution 

Highly protein-bound, mainly to albumin, with affinity for erythrocyte carbonic anhydrase. 

Metabolism 

Undergoes partial hepatic metabolism. 

Elimination/Excretion 

Primarily excreted unchanged by the kidneys; elimination half-life is 45–60 hours, supporting a prolonged duration of action (48–72 hours). 

Pharmacodynamics 

Chlorthalidone exerts its antihypertensive and diuretic effects by inhibiting sodium and chloride reabsorption in the distal tubule, leading to increased excretion of sodium, chloride, and water. This diuretic action reduces extracellular fluid and plasma volume, lowering cardiac output and blood pressure. It also enhances potassium excretion through increased sodium delivery to the distal nephron. Additionally, chlorthalidone may exert cardiovascular benefits by decreasing vascular permeability, reducing platelet aggregation, and promoting angiogenesis, potentially via carbonic anhydrase–dependent mechanisms. 

Adminstartion

Chlorthalidone is administered orally and is available in 15 mg, 25 mg, and 50 mg tablet strengths. It can be used alone or in fixed-dose combinations with drugs like atenolol, azilsartan, or clonidine. The dosage depends on the condition of the treatment.  

Patient Information Leaflet

Generic Name: chlorthalidone 

Pronounced: klor-THAL-i-done 

Why do we use chlorthalidone?  

Chlorthalidone is a thiazide diuretic used to treat high blood pressure (hypertension) and fluid retention (edema). It is effective in managing edema associated with congestive heart failure, liver cirrhosis, kidney disorders, or medication-induced edema from steroids or estrogen. It helps reduce excess fluid by preventing excessive salt absorption in the body.