Effect of clopamide, a thiazide diuretic, on copper and zinc levels in hypertensive patients.

Abstract

Thiazide diuretics, which are often prescribed to treat mild to moderate hypertension, commonly cause an increase in urinary zinc (Zn) excretion. Metabolic interrelationships between Zn and copper (Cu) are known to exist; consequently, Zn might influence Cu levels. This study aims to determine whether or not Cu and Zn levels in hypertensive patients were influenced by treatment with clopamide, a thiazide diuretic. Eight male patients, aged 36-59 and with an average supine diastolic pressure of 95-115 mm Hg, were treated with single daily doses of clopamide 5 mg as monotherapy for 16 weeks. Plasma, erythrocyte (RBC), and mononuclear leukocyte (WBC) levels of Cu and Zn were determined immediately before therapy (week 0) and again at weeks 8 and 16. There was a significant fall in Cu in mononuclear WBCs from 13.25 (SEM = 0.86) to 1.9 fg/cell (SEM = 0.56) (p less than 0.001) and an increase in Zn from 33.87 (SEM = 3.7) to 70.8 fg/cell (SEM = 11.7) (p less than 0.001), with no change in either cell count or measurable cell volume. Plasma Cu levels increased significantly (p less than 0.001), but the Zn levels decreased only slightly (p less than 0.03). Changes in RBC Cu levels during the treatment period were not significantly altered (p less than 0.1). Zn levels in RBCs were significantly (p less than 0.04) lower. It is concluded that treatment with clopamide may induce some changes in Cu and Zn levels in normal hypertensives, particularly in WBCs. Further investigation is needed to determine the extent of this influence.

Changes in Serum Zinc Levels in Relation to Blood Pressure During Anaesthesia

“…levels of zinc registered an increase 8 weeks after initiation of therapy. 4 Genetic predisposition to the effects of anaesthetic agents may be another reason of changes in zinc levels. Hypertension induced by deoxycorticosterone acetate was associated with higher serum zinc levels only in spontaneously hypertensive rats and not in normal rats.…”

Solvatomorph and polymorph screening of clopamide drug and its copper(ii) complex crystals

“…The organic phase was separated and brown single crystals of 9 were obtained after one week by slow evaporation of the solvent in the fridge at 5 °C. (10). Crystals of 10 were prepared in the same way as crystal 9 but instead of ethyl acetate dichloromethane (DCM) was used.…”

“…X-ray diffraction data were collected at 103 K (1-7), 123 K (8) 158 K (9) and 128 K (10) on a Rigaku RAXIS-RAPID II diffractometer. The diffraction measurements were performed using Mo-Kα radiation in all cases, except (1), ( 9) and (10), where a Cu-Kα source was used. Numerical absorption corrections were carried out using the software CrystalClear.…”

“…8 It has also been shown that thiazide diuretics may also cause urinary loss of certain trace elements or modify their levels in blood and may induce changes in the levels of copper in normal hypertensives. 9,10 According to the molecular structure it is noticeable that the carbonyl oxygen and the piperidine nitrogen of the ligand are able to coordinate to metal centres; thus the complexation of clopamide with metal ions in the human body may be responsible for this side effect. On the other hand, various metal complexes can advantageously modify the biological activity of an API compared to the free ligand.…”

“…The outcome of successful crystallization experiments from a homologous series of alcohols allowed us to harvest single crystals of a series of clopamide derivatives (Table 1). The crystal structures of the anhydrous LH (1) (10) were prepared. It has opened up a way to determine how far the molecular conformation and the packing arrangement can preserve isostructurality.…”