DICHLOR 25MG

Indications

• Hypertension
• Edema associated with heart failure
• Edema due to liver cirrhosis
• Edema related to renal dysfunction

Dosage

Adults: The usual initial dose for adults is 12.5 mg once daily, which may be increased to 25 mg if necessary. For hypertension management, doses may vary based on individual patient

Mechanism of action

Chlorthalidone prevents reabsorption of sodium and chloride by inhibiting the Na+/Cl- symporter in the cortical diluting segment of the ascending limb of the loop of Henle. This inhibition leads to an osmotic diuresis, reducing extracellular fluid and plasma volume. The increased sodium delivery to the distal renal tubule causes enhanced potassium excretion through the sodium-potassium exchange mechanism. The antihypertensive effect is attributed to decreased plasma volume, which lowers cardiac output and ultimately reduces blood pressure. Additionally, chlorthalidone may decrease platelet aggregation and vascular permeability, contributing to cardiovascular risk reduction.

Pharmacodynamics

Chlorthalidone exhibits dose-dependent diuretic effects, leading to increased urine output and a reduction in plasma volume. This results in lower cardiac output initially, followed by a decrease in total peripheral resistance, which helps in lowering blood pressure. The drug's ability to affect renal tubular transport of ions also plays a significant role in its therapeutic effects.

Pharmacokinetics

Chlorthalidone is well-absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 2 to 6 hours after oral administration. It has a long half-life, allowing for once-daily dosing. Chlorthalidone is primarily eliminated via the kidneys, with about 60-70% of the dose excreted unchanged in the urine. Its pharmacokinetics can be affected by renal function, necessitating dose adjustments in patients with impaired renal clearance.

Contra-indications

• Hypersensitivity to chlorthalidone or any of its components
• Anuria
• Severe renal impairment
• Electrolyte imbalances, particularly hypokalemia
• Pregnancy (in certain cases)

Adverse effects

• Hypokalemia
• Hyponatremia
• Hyperuricemia
• Gastrointestinal disturbances
• Dizziness
• Headache
• Fatigue
• Rash
• Photosensitivity
• Increased blood sugar levels

Interactions

• Other antihypertensive agents (may enhance hypotensive effects)
• Non-steroidal anti-inflammatory drugs (NSAIDs) (may reduce diuretic effect)
• Lithium (may increase lithium levels)
• Digoxin (enhanced risk of toxicity due to hypokalemia)
• Corticosteroids (may exacerbate hypokalemia)

Precautions

• Monitor electrolyte levels, particularly potassium and sodium
• Use with caution in patients with renal impairment
• Assess volume status in patients at risk of dehydration
• Caution in patients with diabetes mellitus due to possible effects on glucose metabolism
• Consider potential for photosensitivity

Pregnancy

Chlorthalidone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is generally advised to avoid use in the first trimester.

Breast-feeding

Chlorthalidone is excreted in breast milk, caution is advised when administered to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets: 25 mg, 50 mg

Mechanism of action

Chlorthalidone prevents reabsorption of sodium and chloride through inhibition of the Na+/Cl- symporter in the cortical diluting segment of the ascending limb of the loop of Henle. Reduction of sodium reabsorption subsequently reduces extracellular fluid and plasma volume via an osmotic, sodium-driven diuresis. By increasing the delivery of sodium to the distal renal tubule, Chlorthalidone indirectly increases potassium excretion via the sodium-potassium exchange mechanism. The exact mechanism of chlorthalidone's anti-hypertensive effect is under debate, however, it is thought that increased diuresis results in decreased plasma and extracellular fluid volume which therefore requires decreased cardiac output and overall lowers blood pressure. Chlorthalidone has also been shown to decrease platelet aggregation and vascular permeability, as well as promote angiogenesis in vitro, which is thought to be partly the result of reductions in carbonic anhydrase–dependent pathways. These pathways may play a role in chlorthalidone's cardiovascular risk reduction effects. ...ACT BY INHIBITING RENAL TUBULAR TRANSPORT OF VARIOUS IONS. Decreased plasma volume and decreased extracellular fluid volume; decreased cardiac output initially, followed by decreased total peripheral resistance with normalization of cardiac output ... /from table/ ...ANTIHYPERTENSIVE EFFECT OF CHLORTHALIDONE IS THOUGHT TO BE DUE TO DECR CARDIAC OUTPUT. The exact mechanism for reduction of arterial blood pressure by diuretics is not certain. Initially the drugs decrease extracellular volume and cardiac output. However, the hypotensive effect is maintained during long-term therapy because of reduced vascular resistance ... /Diuretics/ For more Mechanism of Action (Complete) data for CHLORTHALIDONE (8 total), please visit the HSDB record page.