Microzide
Hydrochlorothiazide-amiloride causes excessive urinary zinc excretion.

Golik A, Modai D, Weissgarten J, Cohen N, Averbukh Z, Sigler E, Zaidenstein R, Shaked U.

Serum zinc levels and urinary zinc excretion were compared in 15 patients with essential hypertension taking chronically a combination of hydrochlorothiazide and amiloride as monotherapy, eight patients maintained with hydrochlorothiazide alone, and eight control subjects. Serum zinc values were statistically comparable in all three groups. However, urinary zinc excretion was abnormally elevated in the two patient groups. In the dosage used, amiloride did not have a zinc-sparing effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3595066&dopt=Abstract hydrochlorothiazide Microzide



Microzide
Mechanism of attenuated hydrochlorothiazide response during indomethacin administration.

Kirchner KA, Brandon S, Mueller RA, Smith MJ, Bower JD.

Indomethacin antagonizes the natriuretic and chloruretic response to hydrochlorothiazide in most studies. Neither the mechanism nor nephron site of this antagonism has been determined. To identify sites and potential mechanisms, cortical micropuncture was performed during hydrochlorothiazide treatment in control and indomethacin rats. Indomethacin reduced (P less than 0.005) FeCl from 5.20 +/- 0.49% to 2.26 +/- 0.49% (mean +/- SE). MAP, CIn, and plasma volume were not different between groups. SNGFR and fractional proximal fluid and chloride delivery were not different between groups. Fractional chloride delivery to early distal tubules was 10.8 +/- 0.4% in control but 6.2 +/- 0.3% in indomethacin rats (P less than 0.001). Calculated loop chloride reabsorption was greater in indomethacin than control rats during hydrochlorothiazide administration (41.0 +/- 1.6% vs. 34.3 +/- 2.3%; P less than 0.05). Fractional chloride delivery to late distal tubules was 7.8 +/- 0.7% in control and 4.6 +/- 0.3% in indomethacin rats (P less than 0.005), but distal tubule chloride reabsorption was not different between groups. Papillary tissue chloride was less in control than indomethacin rats during hydrochlorothiazide (P less than 0.05). Urinary PGE2 excretion was reduced (P less than 0.001) by indomethacin during hydrochlorothiazide. Thus indomethacin induced reductions in hydrochlorothiazide response result in part from increased chloride reabsorption in the loop segment. This suggests indomethacin antagonizes hydrochlorothiazide by reducing chloride delivery to hydrochlorothiazide's site of action in the distal tubule rather than by effects of indomethacin on hydrochlorothiazide pharmacokinetics.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3599650&dopt=Abstract hydrochlorothiazide Microzide



Microzide
[The stability of hydrochlorothiazide and cyclopenthiazide in various dosage forms. 4. Stability of hydrochlorothiazide injection solutions II]

[Article in German]

Hennig B, Scholz F, Wolf G.

The hydrolytic decomposition of hydrochlorothiazide (1) in an optimized dispensing with polyethyleneglycol 400/ethanol as solvent led to an equilibrium in the isothermic short-term test as well as in the long-term stability test. Corresponding equilibrium concentrations were obtained for forward and back reaction. When comparing the precalculated equilibrium values with the long-term results the evaluation after Van't Hoff proved superior compared with an evaluation after the Arrhenius plot which is only applicable when the equilibrium concentrations are taken into consideration. By adding the decomposition product aminodisulfamide (2) the hydrolysis of 1 can be inhibited completely.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3602070&dopt=Abstract hydrochlorothiazide Microzide



Microzide
The influence of dietary potassium on the renal tubular effect of hydrochlorothiazide in the rat.

Shirley DG, Skinner J, Walter SJ.

The influence of dietary potassium on the natriuretic effect of hydrochlorothiazide was investigated in conscious rats which had access to 0.46 M NaCl solution; the intake of saline was used as an index of the natriuresis. Control rats drank very little saline (less than 1 mmol 24 h-1), whereas animals given hydrochlorothiazide in the food (35 mg kg-1 dry weight) increased their saline intake to approximately 10 mmol 24 h-1. In a third group of rats, on a high-potassium diet (360 mmol kg-1 dry weight vs 60 mmol kg-1 dry weight), the same dose of hydrochlorothiazide increased the saline intake to only 2 mmol 24 h-1. In order to investigate the renal mechanisms involved in these effects, animals were anaesthetized and prepared for micropuncture. Collections were made from late surface convolutions of proximal tubules and from early and late regions of distal tubules. Total glomerular filtration rate, single-nephron filtration rate, and the delivery of sodium to the end of the proximal tubule and to the beginning of the distal tubule were similar in the three groups of rats. In rats on a normal diet, hydrochlorothiazide treatment was associated with an increased delivery of sodium to the end of the distal tubule. No such increase was seen in thiazide-treated rats on a high potassium intake. It is concluded that a high potassium intake reduces the natriuretic effect of hydrochlorothiazide as a result of interference with thiazide-induced inhibition of sodium reabsorption in the distal tubule. The effect of potassium does not depend on changes in sodium handling in other nephron segments. The possible roles of aldosterone and distal tubular potassium secretion in mediating this effect are discussed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3607372&dopt=Abstract hydrochlorothiazide Microzide



Microzide
Comparison of sustained release verapamil and hydrochlorothiazide in hypertension--effect on blood pressure and metabolic variables.

Lehtonen A, Gordin A, Salo H.

The effect of once daily sustained release verapamil (200-400 mg/day) and low dose hydrochlorothiazide (25 mg/day) on blood pressure and metabolic parameters was compared in a cross-over study. The treatment periods lasted 6 months. The antihypertensive efficacy of verapamil was comparable to that of low dose hydrochlorothiazide. Plasma total cholesterol, LDL cholesterol, HDL cholesterol or triglycerides did not change significantly from the values at the end of the drug free run-in period either on verapamil or on hydrochlorothiazide. Statistically, serum insulin decreased significantly with verapamil (13.4 +/- 4.3 U/ml, m +/- SD) when compared with both the wash-out (16.2 +/- 5.7 U/ml) and hydrochlorothiazide (17.1 +/- 6.5 ml) periods. There were no significant differences in fasting blood glucose between the treatment periods. Serum uric acid concentration increased significantly (from 266 +/- 64 mumol/l) after the wash-out period (to 307 +/- 92 mumol/l) after hydrochlorothiazide, but did not change on verapamil (270 +/- 75 mumol/l). Serum potassium decreased significantly from 3.96 +/- 0.39 mmol/l after the wash-out period to 3.67 +/- 0.37 mmol/l on hydrochlorothiazide, but did not change on verapamil (3.94 +/- 0.28 mmol/l).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3623734&dopt=Abstract hydrochlorothiazide Microzide