Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1     Pharmacodynamic properties
Pharmacotherapeutic group: Diuretic and potassium-sparing agent ATC code: C03EA01 
Mechanism of action
Hydrochlorothiazide is a diuretic with antihypertensive properties. It acts by inhibiting the renal tubular reabsorption of sodium and chloride ions, which are excreted with an accompanying volume of water. Potassium excretion is also promoted.

Amiloride hydrochloride is a potassium-sparing diuretic. It also promotes the excretion of sodium and chloride, but it reduces the excretion of potassium.

Non-melanoma skin cancer
Based on available data from epidemiological studies, cumulative dose- dependent association between hydrochlorothiazide and NMSC has been observed. One study included a population comprised of 71,533 cases of BCC and of 8,629 cases of SCC matched to 1,430,833 and 172,462 population controls, respectively. High hydrochlorothiazide use (≥50,000 mg cumulative) was associated with an adjusted OR of 1.29 (95% CI: 1.23-1.35) for BCC and 3.98 (95% CI: 3.68-4.31) for SCC. A clear cumulative dose response relationship was observed for both BCC and SCC. Another study showed a possible association between lip cancer (SCC) and exposure to hydrochlorothiazide: 633 cases of lip-cancer were matched with 63,067 population controls, using a risk-set sampling strategy. A cumulative dose-response relationship was demonstrated with an adjusted OR 2.1 (95% CI: 1.7- 2.6) increasing to OR 3.9 (3.0-4.9) for high use (~25,000 mg) and OR 7.7 (5.7- 10.5) for the highest cumulative dose (~100,000 mg) (see also section 4.4).

Pharmacokinetic Properties

5.2     Pharmacokinetic properties
Hydrochlorothiazide
About 70% of an oral dose of hydrochlorothiazide is absorbed. It has a plasma half-life of 5.6 to 14.8 hours with a subsequent longer terminal half-life.

Peak plasma concentration reached in 1.5 to 3 hours, with diuresis lasting for 12 hours.

It is excreted unchanged in the urine. It crosses the placental barrier and is secreted in breast milk.

Amiloride
About 50% of an oral dose of amiloride hydrochloride is absorbed. It has a plasma half- life of about 6 to 9 hours, but its effects may persist for up to 48 hours after a single dose.

It is excreted unchanged in the urine and faeces. Peak serum levels reached in 4 hours.