Pharmacodynamics and mechanism of action
Chlorthalidone acts by binding to the Na+/Cl- symporter channel in the renal tubules, blocking the reabsorption of sodium and chloride, and the ions are excreted in the urine. The osmotic effect results in increased excretion of water as well. This increased excretion of fluid results in a decrease in blood volume and thus a decrease in blood pressure.
Chlorthalidone is absorbed via the gastrointestinal tract after peroral administration and is rapidly absorbed. It concentrates more in erythrocytes and diffuses from them only slowly back into the serum, giving it a relatively large volume of distribution. Approximately 75 percent of the drug is bound to plasma proteins, with 58 percent of the drug bound to albumin. Approximately 50 percent of the administered dose is excreted unchanged by the kidney. The other half is metabolized by the liver and also excreted by the kidneys. The half-life is approximately 40-50 hours.
There are a number of drug interactions that must be considered when taking chlorthalidone. For example, it may decrease the effectiveness of insulin and other antidiabetic drugs and slow the excretion of lithium, which may increase the risk of side effects due to its low therapeutic range. Dose adjustment should be performed in this case.
Attention should also be paid to the synergistic effect of the agent together with other antihypertensives. Joint use, if unintentional, may result in excessive blood pressure reduction and associated symptoms.