BACKGROUND: Thiazides have been used in nephrogenic diabetes insipidus (NDI) patients to decrease urine volume, but the mechanism of antidiuretic effect is not known yet. Recently, it has been demonstrated that abundance of aquaporin-2 (AQP2) was decreased in lithium induced NDI. We performed this study to investigate the effect of hydrochlorothiazide (HCTZ) in lithium induced NDI rats and the change of AQP2 expression. METHODS: NDI was induced in 7 male Spraque- Dawley rats by feeding lithium carbonate containing rat chow (40 mmol/kg) for 5 weeks. 4 rats were control group. HCTZ 3.75 mg/day (n=3 among lithium treated; Li+TZ) or vehicle (n=4 among lithium treated and control; Li and Control, respectively) was infused to the rats through osmotic minipump for the last 7 days. Urine volume and urine osmolality were measured. Kidneys were processed for immunohistochemistry and immunoblotting using antibody to AQP2. RESULTS: Li+TZ showed decreased urine volume (46+/-11 mL/day for Li+TZ vs. 127+/-1 mL/day for Li, p<0.05) and higher urine osmolality (557+/-139 mmol/kgH2O for Li+TZ vs. 207+/-9 mmol/kgH2O for Li, p<0.05) comparing to Li. In semi-quantitative immunoblotting using whole kidney homogenate, Li+TZ showed increase in AQP2 expression comparing to Li (39+/-2% for Li+TZ vs. 20+/-9% for Li, p<0.05, % of normal controls). In immunohistochemistry, AQP2 expression in cortex was markedly decreased after lithium treatment. But, AQP2 expression was slightly increased after HCTZ treatment. CONCLUSION: HCTZ treatment partially increased urine concentrating ability and AQP2 expression in rats with lithium induced NDI. We concluded that partial improvement in urine concentrating ability might be associated with upregulation of AQP2.
Animals ; Antidiuretic Agents ; Aquaporin 2* ; Diabetes Insipidus, Nephrogenic* ; Humans ; Hydrochlorothiazide* ; Immunoblotting ; Immunohistochemistry ; Kidney ; Kidney Concentrating Ability ; Lithium Carbonate ; Lithium* ; Male ; Osmolar Concentration ; Rats* ; Thiazides ; Up-Regulation

Hypokalemia is a common metabolic cause of rhabdomyolysis. Although treatment with thiazide causes hypokalemia frequently, hypokalemic rhabdomyolysis after administration with thiazide is very rare. Here we report two cases of hypokalemic rhabdomyolysis due to thiazide treatment. A 50-year-old woman who had been treated with thiazide for hypertension was admitted due to quadriplegia. The patient had a potassium level of 1.5 mEq/L, a creatinine phosphokinase (CPK) level of 21,346 IU/L, and a lactic dehydrogenase level (LDH) of 2,389 IU/L. An 80-year-old man who had been treated with thiazide for hypertension was admitted due to generalized weakness. His potassium level was 1.9 mEq/L, CPK was 29,000 IU/L, and LDH was 2,393 IU/L. There were no any other causes of rhabdomyolysis except hypokalemia due to thiazide treatment for both patients. With adequate hydration and potassium replacement, hypokalemic rhabdomyolysis recovered completely without sequele.
Aged, 80 and over ; Creatinine ; Female ; Humans ; Hypertension ; Hypokalemia ; Middle Aged ; Oxidoreductases ; Potassium ; Quadriplegia ; Rhabdomyolysis* ; Thiazides

Thizide diuretics which are widely used nowadays, are considered to be drugs of first choice of antihypertensive agents, due to their slow and useful diuretic effects in hypertensive patients. But their adverse effects have been noted as hypokalemia and hyperuricemia. A newly developed non-thiazide diuretic agent, Sulfamoyl benzamide has been known as slow effective and safe diuretics as thiazides through several previous studies. And all the studies showed no serious hypokalemia or hyperuricemia. Authors administrated Sulfamoyl benzamide to 20 patients of essential hypertension for 4 weeks, who visited the Department of Internal Medicine of han Yang University Hospital from Nov.82' to May 83', and observed its hypotensive effect and its adverse effect as follows. 1) Before Sufamoyl benzamide administeration, mean arterial systolic pressure and mean arterial diastolic pressure of 20 patients of essential hypertension were 165.5+/-7.23 mmHg and 99.8+/-4.93 mmHg, respectively. The Mean Arterial Pressure(MAP) was 121.7+/-4.48 mmHg. After 4 weeks of treatment, the mean arterial systolic pressure, mean arterial diastolic pressure, and MAP were decreased to 148.3+/-10.64 mmHg(p<0.01), 94.3+/-6.40 mmHg(p<0.01), and 112.1+/-6.66 mmHg(p<0.01), respectively. 2) After 4 weeks of treatment, the hypotensive effect on each of 20 hypotensive patients was evaluated using our arbitrary scoring system which is decided by the degree of reduction of arterial systolic pressure and diastolic pressure. In all patients, useful hypotensive effect was noted. Out of 20 patients, 11 patients(55%) were 'Mild effective', 6 patients(30%) were 'Moderate effective', and 3 patients(15%) were 'Mild effective'. By MAP, the meaningful hypotensive effect was observed in 12 patients(60%), and there were a 'Mild effect' in 6 of 12 patients, a 'Moderate effect' in 4 of 12 patients, and a 'Marked effect' in 2 of 12 patients. 3) There was no adverse side effect except mild dizziness in only 1 patient, which was improved spontaneously after reduction of dosage of Sulfamoyl benzamide from 30 mg to 15mg whitout any specific treatment.
Antihypertensive Agents ; Blood Pressure ; Diuretics* ; Dizziness ; Humans ; Hypertension ; Hyperuricemia ; Hypokalemia ; Internal Medicine ; Thiazides

TRPV5 is believed to play an important role in the regulation of urinary calcium excretion. We assessed the effects of hydrochlorothiazide (HCTZ) on the expression of TRPV5, calbindin-D28K, and several sodium transporters in hypercalciuric rats. Sprague- Dawley rats were divided into 4 groups; control, HCTZ, high salt, and high salt with HCTZ group in experiment 1; control, HCTZ, high calcium (Ca), and high Ca with HCTZ group in experiment 2. To quantitate the expression of TRPV5, calbindin- D28K, and sodium transporters, western blotting was performed. In both experiments, HCTZ significantly decreased urinary calcium excretion. TRPV5 protein abundance decreased in all hypercalciuric rats, and restored by HCTZ in both high salt with HCTZ and high Ca with HCTZ group. Calbindin-D28K protein abundance increased in the high salt and high salt with HCTZ groups, but did not differ among groups in experiment 2. Protein abundance of NHE3 and NKCC2 decreased in all hypercalciuric rats, and were restored by HCTZ in only high Ca-induced hypercalciuric rats. In summary, protein abundance of TRPV5, NHE3, and NKCC2 decreased in all hypercalciuric rats. The hypocalciuric effect of HCTZ is associated with increased protein abundance of TRPV5 in high salt or calcium diet-induced hypercalciuric rats.
Animals ; Biological Transport ; Calcium/urine ; Calcium Channels/chemistry ; Calcium-Binding Protein, Vitamin D-Dependent/*biosynthesis ; Hydrochlorothiazide/pharmacology ; Hypercalciuria/*therapy ; Male ; Models, Biological ; Rats ; Rats, Sprague-Dawley ; Sodium/*metabolism ; Sodium-Hydrogen Antiporter/chemistry ; Sodium-Potassium-Chloride Symporters/metabolism ; TRPV Cation Channels/*biosynthesis/chemistry ; Thiazides/*pharmacology

Several studies have documented that various agents can induce diabetes mellitus, such as steroids, thiazides, anti-psychotic agents, and anti-viral agents. Many antiviral agents are also reported to impair insulin resistance and induce diabetes mellitus in patients infected with human immunodeficiency virus (HIV). However, there are no reports of diabetes mellitus induced by clevudine, one of the antiviral agents used to treat chronic hepatitis B virus (HBV) infection. We report a case of diabetes mellitus induced by clevudine in a patient with chronic hepatitis B.
Antiviral Agents ; Arabinofuranosyluracil ; Diabetes Mellitus ; Hepatitis B, Chronic ; Hepatitis, Chronic ; HIV ; Humans ; Insulin Resistance ; Steroids ; Thiazides ; Viruses

BACKGROUND: Hypertension is a major risk factor for cardiovascular disease. The prevalence of hypertension in the Western Pacific Region is 37% of adults older than 24, while in the Philippines it is 25% of adults 21 years old and above. Several guidelines have been developed for the management of hypertension. All these guidelines have recommendations for assessment and treatment.
OBJECTIVES: The overall objective of the development and implementation of this clinical pathway is to improve outcomes of patients with hypertension seen in family and community practice.
METHODS: The PAFP Clinical Pathways Group reviewed published medical literature to identify, summarize, and operationalize the clinical content of diagnostics, interventions and clinical indicators or outcomes to develop an evidence-based clinical pathway in family medicine practice. The group developed a time-related representation of recommendations on patient care processes, in terms of history and physical examination, laboratory tests, pharmacologic and non-pharmacologic interventions as well as social and community strategies to treat hypertension and prevent complications.
RECOMMENDATIONS: Recommendations were made based on the number of visits. During the first visit, all adult patients consulting at the clinic should be screened for hypertension with appropriate BP measurement. A thorough history focusing on symptoms, family history using genogram, smoking and other lifestyle and co-existing chronic disease and a thorough physical examination focusing on the weight/BMI, waist/hip ration, funduscopy, neurological, cardiac, renal and peripheral arteries should be done. For the laboratory, request for 12-lead ECG, urinalysis, FBS, creatinine, serum K and lipid profile to determine co-morbidities and baseline values. If the patient is already diagnosed hypertensive, start/continue medications with either or a combination of thiazide-type diuretic, calcium channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blocker depending on co-morbidities or side effects. But if there is a need for further confirmation, no medication is warranted. Educate the patient about hypertension, risk factors and complications. If medications were prescribed, explain the dose, frequency, intended effect, possible side effects and importance of medication adherence. Lifestyle modifications focusing on weight control, exercise and smoking cessation should be advised. During the first first visit is expected that the patient is aware of the diagnosis of hypertension, its risks factors and complications to encourage compliance.
IMPLEMENTATION: Education, training and audit are recommended strategies to implement the clinical pathway.

Human ; Angiotensin-converting Enzyme Inhibitors ; Smoking Cessation ; Medication Adherence ; Sodium Chloride Symporter Inhibitors ; Hypertension ; Chronic Disease ; Lipids ; Thiazides ; Arteries

The importance of thiazide-induced hyponatremia (TIH) is reemerging because thiazide diuretic prescription seems to be increasing after the guidelines recommending thiazides as first-line treatment of essential hypertension have been introduced. Thiazide diuretics act by inhibiting reabsorption of Na+ and Cl- from the distal convoluted tubule by blocking the thiazide-sensitive Na+/Cl- cotransporter. Thus, they inhibit electrolyte transport in the diluting segment and may impair urinary dilution in some vulnerable groups. Risk factors predisposing to TIH are old age, women, reduced body masses, and concurrent use of other medications that impair water excretion. While taking thiazides, the elderly may have a greater defect in water excretion after a water load compared with young subjects. Hyponatremia is usually induced within 2 weeks of starting the thiazide diuretic, but it can occur any time during thiazide therapy when subsequent contributory factors are complicated, such as reduction of renal function with aging, ingestion of other drugs that affect free water clearance, or changes in water or sodium intake. While some patients are volume depleted on presentation, most appear euvolemic. Notably serum levels of uric acid, creatinine and urea nitrogen are usually normal or low, suggestive of syndrome of inappropriate secretion of antidiuretic hormone. Despite numerous studies, the pathophysiological mechanisms underlying TIH are unclear. Although the traditional view is that diuretic-induced sodium or volume loss results in vasopressin-induced water retention, the following 3 main factors are implicated in TIH: stimulation of vasopressin secretion, reduced free-water clearance, and increased water intake. These factors will be discussed in this review.
Aged ; Aging ; Creatinine ; Diuretics ; Drinking ; Eating ; Female ; Humans ; Hypertension ; Hyponatremia ; Nitrogen ; Prescriptions ; Retention (Psychology) ; Risk Factors ; Sodium ; Sodium Chloride Symporter Inhibitors ; Thiazides ; Urea ; Uric Acid ; Vasopressins ; Water

Gitelman syndrome is a condition caused by a mutation of the thiazide sensitive Na-Cl cotransporter gene on the distal convoluted tubule. It results in a variety of clinical features, including hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. It is often diagnosed in asymptomatic adults presented with unexplained hypokalemia; however, it is sometimes associated with muscular cramps, numbness, fatigue, weakness, or paralysis. We experienced a case of rheumatoid arthritis accompanied by Gitelman syndrome, presented with hand tremor. We diagnosed her using renal clearance study and genetic analysis. Here, we report our experiences regarding this case along with a literature review.
Adult ; Alkalosis ; Arthritis, Rheumatoid* ; Fatigue ; Furosemide ; Genetic Testing ; Gitelman Syndrome* ; Hand ; Humans ; Hypesthesia ; Hypokalemia ; Muscle Cramp ; Paralysis ; Solute Carrier Family 12, Member 3 ; Thiazides ; Tremor

Gitelman syndrome is a condition caused by a mutation of the thiazide sensitive Na-Cl cotransporter gene on the distal convoluted tubule. It results in a variety of clinical features, including hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. It is often diagnosed in asymptomatic adults presented with unexplained hypokalemia; however, it is sometimes associated with muscular cramps, numbness, fatigue, weakness, or paralysis. We experienced a case of rheumatoid arthritis accompanied by Gitelman syndrome, presented with hand tremor. We diagnosed her using renal clearance study and genetic analysis. Here, we report our experiences regarding this case along with a literature review.
Adult ; Alkalosis ; Arthritis, Rheumatoid ; Fatigue ; Furosemide ; Genetic Testing ; Gitelman Syndrome ; Hand ; Humans ; Hypesthesia ; Hypokalemia ; Muscle Cramp ; Paralysis ; Solute Carrier Family 12, Member 3 ; Thiazides ; Tremor

The effects of several antihypertensive drugs on bone mineral density (BMD) and micro-architectural changes in ovariectomized (OVX) mice were investigated. Eight-week-old female C57/BL6 mice were used for this study. Three days after ovariectomy, mice were treated intraperitoneally with nifedipine (15 mg/kg), telmisartan (5 mg/kg), enalapril (20 mg/kg), propranolol (1 mg/kg) or hydrochlorothiazide (12.5 mg/kg) for 35 consecutive days. Uterine atrophy of all mice was confirmed to evaluate estrogen deficiency state. BMD and micro-architectural analyses were performed on tibial proximal ends by micro-computed tomography (micro-CT). When OVX mice with uterine atrophy were compared with mice without atrophy, BMD decreased (P < 0.001). There were significant differences in BMD loss between different antihypertensive drugs (P = 0.005). Enalapril and propranolol increased BMD loss in mice with atrophied uteri compared with control mice. By contrast, thiazide increased BMD in mice with uterine atrophy compared with vehicle-treated mice (P = 0.048). Thiazide (P = 0.032) and telmisartan (P = 0.051) reduced bone loss and bone fraction in mice with uterine atrophy compared with the control. Thiazide affects BMD in OVX mice positively. The reduction in bone loss by thiazide and telmisartan suggest that these drugs may benefit menopausal women with hypertension and osteoporosis.
Animals ; Antihypertensive Agents/*pharmacology ; Atrophy ; Benzimidazoles/pharmacology ; Benzoates/pharmacology ; Bone Density/*drug effects ; Enalapril/pharmacology ; Female ; Mice ; Mice, Inbred C57BL ; Ovariectomy ; Propranolol/pharmacology ; Thiazides/pharmacology ; Tibia/radiography ; Tomography, X-Ray Computed ; Uterus/anatomy & histology/pathology