Microzide
Pressure and humoral changes induced by atenolol and hydrochlorothiazide + amiloride, alone and in free combination. A comparative between-patient study.

Salvadeo A, Villa G, Segagni S, Piazza V, Galli F.

The authors have performed a between-patient study in 76 patients with mild or moderate essential arterial hypertension, with the aim of comparing the results of atenolol 100 mg daily, hydrochlorothiazide 50 mg + amiloride 5 mg 1 tablet daily, and the combination of the above two agents at the same daily doses. Thirty-one patients received the free combination diuretic-beta-blocker throughout the study period; 26 patients non-responders to atenolol 100 mg daily (supine diastolic blood pressure greater than 90 mmHg) after a one-month treatment period received the above combination for a further four months; and 19 patients non-responders to hydrochlorothiazide 50 mg + amiloride 5 mg, 1 tablet daily, after a one-month treatment period received the above combination for a further four months. In the patients who were non-responders to either atenolol or the diuretic, supine and upright blood pressure showed a further and clinically consistent decrease as a result of the combination therapy. A similar consistent decrease was seen in the patients receiving the combination therapy throughout the study. Plasma levels of glucose, urea, creatinine, sodium, potassium and uric acid were not modified either by the single agents or during administration of the combination therapy. In particular, plasma potassium concentration did not show any statistical or clinical changes. Any side-effects were of little clinical importance and never required discontinuation of therapy. In conclusion, atenolol combined with hydrochlorothiazide + amiloride (100 mg + 50 mg + 5 mg) provides an effective and well tolerated blood pressure control in most patients with mild or moderate arterial hypertension, including non-responders to diuretic or beta-blocker alone.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6678831&dopt=Abstract hydrochlorothiazide Microzide



Microzide
Quantum-chemical and physico-chemical properties of hydrochlorothiazide.

Orita Y, Ando A, Yamabe S, Nakanishi T, Arakawa Y, Abe H.

The electronic states of hydrochlorothiazide and its related molecules were obtained by CNDO/2 (CNDO = complete neglect of differential overlap), and van der Waals volume and hydrophobic parameters of the substituent of the 6th position in the benzothiadiazine were estimated. The results were discussed from the viewpoint of the structure-activity relationship analysis. Rather lower LUMO (lowest unoccupied molecular orbital level) of hydrochlorothiazide which had been predicted by the iterated Huckel's Molecular Orbital Method was confirmed by CNDO/2 calculation. The introduction of the sulfamoyl group to the 7th position in the benzothiadiazine ring brought out a negative formal charge for the 7th position. The diuretic effect of the substituent of the 6th position in the benzothiadiazine ring was analysed with respect to its van der Waals volume and its hydrophobic parameter. Van der Waals volume seemed to have a close relationship to diuretic activity. The highest correlated coefficient of the regression equation for the structure-activity relationship was obtained using the formal charge of the 7th position in the benzothiadiazine ring, van der Waals volume and the hydrophobic parameter of the substituent of the 6th position. On the basis of result obtained, the model for the action site of hydrochlorothiazide was proposed, consisting of a rather larger, lipophilic hole and an electrostatic interaction site in the tubular membrane.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6683545&dopt=Abstract hydrochlorothiazide Microzide



Microzide
Bioavailability of hydrochlorothiazide from tablets and suspensions.

Patel RB, Patel UR, Rogge MC, Shah VP, Prasad VK, Selen A, Welling PG.

The bioavailability of hydrochlorothiazide was determined following single oral 25-, 50-, 100-, and 200-mg tablet and suspension doses in 12 healthy male volunteers. Plasma and urine levels of hydrochlorothiazide were determined by HPLC. Plasma levels of hydrochlorothiazide were satisfactorily described by a triexponential function. Mean peak plasma levels, Cmax (127-135, 270-280, and 437-490 ng/mL from the 25-, 50-, and 100-mg doses, respectively) were dose proportional, as were areas under plasma profiles, AUC0----36. Mean percentage recovery of unchanged hydrochlorothiazide in 48-h urine samples accounted for 50-59, 54-55, 60-63, and 54-57% of the 25-, 50-, 100-, and 200-mg doses, respectively. There were no significant differences among these values. Correlation coefficients between 48-h urinary recovery of hydrochlorothiazide and the plasma values (Cmax and AUC0----36) for the 25-, 50-, and 100-mg doses were 0.73 and 0.84. There were no differences in the net increases in electrolyte excretion among the treatments during the 0-12-h postdose period. The systematic availability of hydrochlorothiazide, unlike that of chlorothiazide, is dose proportional in the therapeutic range.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6716243&dopt=Abstract hydrochlorothiazide Microzide



Microzide
Response to indomethacin and hydrochlorothiazide in nephrogenic diabetes insipidus.

Monnens L, Jonkman A, Thomas C.

Four boys with classical nephrogenic diabetes insipidus have been treated by indomethacin, by hydrochlorothiazide, and by the combination of indomethacin and hydrochlorothiazide. Hydrochlorothiazide treatment was slightly more effective than indomethacin treatment in reducing the urine volume and increasing the urine osmolality. The combination of indomethacin and hydrochlorothiazide appeared to be additive and especially helpful in infants and young children before the autonomy of drinking.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6723207&dopt=Abstract hydrochlorothiazide Microzide



Microzide
Photolytic decomposition of hydrochlorothiazide.

Tamat SR, Moore DE.

Hydrochlorothiazide decomposes upon irradiation with near-UV light (lambda greater than 310 nm) both in methanol and aqueous solutions. In the photolysis the chlorine substituent is removed to be replaced by either--H or--OR from the solvent ROH. Hydrolysis of the thiadiazine ring is superimposed upon the dechlorination. The presence of oxygen inhibits the decomposition. The mechanism of the photolysis is suggested to involve cation radical formation which facilitates the hydrolysis step. 5-Chloro-2,4-disulphonamido-aniline, the normal hydrolysis product from hydrochlorothiazide, is also susceptible to photolytic dechlorination by a similar mechanism.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6834257&dopt=Abstract hydrochlorothiazide Microzide