Thiazide and thiazide-like diuretics in nephrolithiasis / Diuréticos tiazídicos e tiazídicos-like na nefrolitíase

Abstract Thiazide and thiazide-like diuretics are widely used for the management of hypercalciuria among stone-forming patients. Although the effects of different thiazides should be relatively similar in terms of prevention of stone recurrence, their potency and side effects may differ. However, there is scarce data concerning the metabolic and bone effects of these agents among recurrent nephrolithiasis patients with hypercalciuria. The aim of this update article was to compare our experience in the use of thiazide and thiazide- like diuretics with that of the current literature, concerning their anticalciuric properties and consequent reduction of recurrent stone formation. Their impact on bone mass and potential side effects were also discussed.

Resumo Diuréticos tiazídicos e tiazídicos-like são amplamente usados para o tratamento da hipercalciúria em pacientes com formação de cálculos. Embora os efeitos dos diferentes tiazídicos devam ser relativamente semelhantes em termos de prevenção da recorrência do cálculo, sua potência e efeitos colaterais podem ser diferentes. No entanto, há poucos dados sobre os efeitos metabólicos e ósseos desses agentes em pacientes com nefrolitíase recorrente com hipercalciúria. O objetivo deste artigo de atualização foi comparar nossa experiência quanto ao uso de tiazídicos e tiazídicos-like com a publicada na literatura atual, no que diz respeito às suas propriedades anticalciúricas e consequente redução da formação de cálculos recorrentes. Discutimos também seu impacto na massa óssea e potenciais efeitos colaterais.

Polifarmácia e cognição em pacientes com idade avançada / Polypharmacy and cognition in elderly patients

Objetivo: Avaliar a prevalência da polifarmácia e da prescrição de medicações inapropriadas, bem como suas associações com a capacidade cognitiva e funcional do idoso. Métodos: Estudo observacional transversal, no qual foram analisadas as medicações prescritas em 141 prontuários para pacientes acima de 50 anos, em associação com testes que quantificaram a capacidade funcional e cognitiva deles. Resultados: Observou-se média de 4,41 medicamentos por paciente, sendo que 0,41 deles foram considerados inapropriado, segundo o critério de Beers. Verificou-se também relação estatisticamente significativa quanto ao número de medicações e testes que mediam a capacidade funcional e cognitiva dos idosos. Conclusão: O aumento da polifarmácia e da prescrição de medicações potencialmente inadequadas acarretou significativa piora da capacidade cognitiva e funcional do idoso

Objective: To evaluate the prevalence of polypharmacy and of the prescription of inappropriate medications, as well as their associations with the cognitive and functional capacity of the elderly. Methods: Cross-sectional observational study which analyzed the drugs prescribed in 141 medical records for patients over 50 years of age, associated with tests that quantified their functional and cognitive capacity. Results: An average of 4.41 medications per patient was observed, and 0.41 were considered inappropriate according to the Beers criteria. There was also a statistically significant relation regarding the number of medications and tests that measure the functional and cognitive capacity of the elderly. Conclusion: The increase in polypharmacy and in the prescription of potentially inappropriate medications led to a significant impairment of the cognitive and functional capacity of the elderly

Edema pulmonar agudo no cardiogénico secundario a hidroclorotiazida: reporte de un caso y revisión de la literatura / Hydrochlorothiazide induced non-cardiogenic acute pulmonary edema: a case report

Las tiazidas son fármacos frecuentemente usados en la terapia de la hipertensión arterial. Las reacciones adversas de riesgo vital como shock y edema pulmonar agudo son raros. Comunicamos el caso de una mujer de 55 años de edad atendida en Hospital de Puerto Montt, quien tras dos horas de ingerir hidroclorotiazida presentó disnea. Los exámenes de laboratorio generales e imágenes muestran cuadro concordante con edema pulmonar agudo no cardiogénico. Además de la suspensión del fármaco, se realizó soporte hemodinámico y ventilatorio no invasivo, evidenciándose resolución del cuadro a las 48 h. La paciente fue dada de alta 3 días después de su ingreso sin sintomatología.

Thiazides are drugs often used in management of high arterial blood pressure. Shock and acute pulmonary edema are rarely described as adverse reactions related to this drug. We report the case of a 55 years-old woman admitted at Hospital de Puerto Montt, Chile. Two hours after having her first dose of hydrochlorothiazide she presented dyspnea. Laboratory tests and images support the diagnosis of non-cardiogenic pulmonary edema. Resolution of her clinical picture was observed 48 hours after hydrochlorothiazide administration was discontinued and hemodynamic and non invasive ventilation support were supplied. The patient was discharged without symptoms, 3 days after entering to hospital.

Clinical pathways for the management of hypertension in family and community practice

@#<p style="text-align: justify;"><strong>BACKGROUND:</strong> 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.<br /><strong>OBJECTIVES:</strong> 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.<br /><strong>METHODS:</strong> 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.<br /><strong>RECOMMENDATIONS:</strong> 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.<br /><strong>IMPLEMENTATION:</strong> Education, training and audit are recommended strategies to implement the clinical pathway.</p>

Clinical pathways for the management of hypertension in family and community practice

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.

Rheumatoid arthritis accompanied by Gitelman syndrome / 영남의대학술지

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.

Rheumatoid arthritis accompanied by Gitelman syndrome / 영남의대학술지

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.

The Effects of Antihypertensive Drugs on Bone Mineral Density in Ovariectomized Mice

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.

The Effects of Antihypertensive Drugs on Bone Mineral Density in Ovariectomized Mice

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.

Efeito da associação de losartan e hidroclorotiazida em modelo experimetal de nefrologia crônica resultante da administração de losartan durante a lactação (LLact) / Combined losartan (L) and hydrochlorothiazide (H) prevent progression of renal damage in chronic kidney disease (CKD) resulting from L treatment during lactation (LLact)

Descrevemos recentemente um novo modelo de DRC, baseado nos efeitos adversos da administração de L na lactação (LLact). Os objetivos do presente estudo foram; caracterizar os mecanismos patológicos envolvidos com a nefropatia do LLact e investigar se o extraordinário efeito renoprotetor obtido com a associação L+H no modelo NX seria reproduzido no modelo LLact. Utilizamos 20 ratas Munich-Wistar lactantes, com 6 filhotes cada. As matrizes receberam L, 250mg/Kg/d durante a amamentação e a droga atingiu a prole via leite materno. Os filhotes machos foram acompanhados até os 7 meses de vida, quando se verificou; pressão caudal, albuminúria, creatinina sérica, glomerulosclerose, expansão intersticial, proliferação celular, presença de miofibroblastos intersticiais e rarefação capilar. Os animais LLact restantes foram divididos em 3 novos grupos: LLact+V, mantido sem tratamento, LLact+L, LLact+H, e LLact+LH. Os parâmetros foram reavaliados após 3 meses nesses grupos e também em animais controle (C). Os ratos, LLact apresentaram hipertensão, albuminuria, glomerulosclerose (GS) e lesão intersticial com inflamação e fibrose aos 10 meses de vida. O tratamento com L+H na vida adulta limitou a hipertensão, albuminúria, GS, proliferação intersticial e infiltração de miofibroblastos. Porém, a renoproteção obtida pela associação foi moderada em relação aos resultados previamente obtidos com o modelo NX, especialmente no tocante ao comprometimento tubulointersticial.

We recently standardized a severe CKD model based on impaired nephrogenesis by suppression of angiotensin II (Ang II) activity during lactation (LLact). In the present study we sought to gain further insight into the mechanisms associated with the LLact model and to verify if the renoprotection obtained with the association of the Ang II receptor blocker, Losartan (L), and Hydrochlorothiazide (H), which arrested renal injury in the remnant kidney model, could be also obtained in the LLact model. Twenty Munich-Wistar dams, each nursing 6 pups, received L, 250 mg/kg/d, until weaning. The male LLact offspring remained untreated until 7 months of age, when renal functional and structural parameters were studied in 17 of them, used as pretreatment control (LLactPre), followed no further. The remaining rats were divided in groups: LLact+V, untreated, LLact+L, given L, 50 mg/kg/day, now as a therapy, LLact+H, given H, 6mg/kg/day and LLact+LH, given L and H. All the parameters were reassessed 3 months later in these groups and in agematched controls (C). At this time, LLact rats exhibited hypertension, albuminuria, glomerulosclerosis (GS), interstitial expansion and inflammation, enhanced cell proliferation, myofibroblast infiltration, and creatinine retention. LH therapy normalized blood pressure, albuminuria, GS, and limited interstitial cell proliferation and -smooth muscle actin (-SMA) accumulation. However, LH renoprotection achieved with the LLact model was only mild if compared previous studies with the 5/6 renal ablation model.

Clevudine induced diabetes mellitus in a patient with chronic hepatitis B / 대한내과학회지

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.

Thiazide-Induced Hyponatremia

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.

Effects of Thiazide on the Expression of TRPV5, Calbindin-D28K, and Sodium Transporters in Hypercalciuric Rats

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.

Serum uric acid prevalence and changes post various antihypertensive agents in patients with essential hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>To survey the prevalence of hyperuricacidemia and serum uric acid (SUA) changes and electrolyte changes after 6 weeks antihypertensive treatment with thiazide diuretics, losartan or losartan+hydrochlorothiazide (Hyzaar) in patients with essential hypertension (EH).</p><p><b>METHODS</b>A total of 1080 consecutive EH patients [662 males, mean age (60.9 +/- 12.3) years] who seeked for medical consultation in study hospitals in Fuzhou city during October 2004 and October 2006 were included in this study. The blood pressure before and after antihypertensive treatments were obtained in 1000 patients, and the renal function and electrolyte before and after antihypertensive treatments were obtained in 600 patients. Patients with SBP > 140 and/or DBP > 90 mm Hg 2 weeks after initial antihypertensive agents were cotreated with felodipine, patients with SBP > 140 and/or DBP > 90 mm Hg 4 weeks after initial antihypertensive agents were cotreated with beta and/or alpha blockers.</p><p><b>RESULTS</b>The prevalence of hyperuricacidemia in EH patients was 25.83% (279/1080). Body mass index (BMI) and creatinine were significantly higher while creatinine clearance rate (Ccr) calculated by Cockcroft-Gault equation was significantly lower in EH patients with hyperuricacidemia than EH patients without hyperuricacidemia (all P < 0.05). Similar antihypertensive effects were observed in EH patients treated with thiazide diuretics (n = 200), losartan (n = 324) or losartan + hydrochlorothiazide (Hyzaar, n = 476) and SBP was lower than 140 mm Hg in 69.40% and DBP was less than 90 mmHg in 85.30% EH patients 6 weeks after antihypertensive treatments. SUA was significantly increased (43.81 micromol/L +/- 71.79 micromol/L) low dose diuretics group (P < 0.01 vs. pretreatment), significantly reduced (44.96 micromol/L +/- 90.63 micromol/L) in losartan group (P < 0.0001 vs. pretreatment) and remained unchanged in Hyzaar group (7.46 +/- 84.72 micromol/L, P > 0.05 vs. pretreatment). Serum potassium was significantly decreased (0.30 +/- 0.44 mmol/L) in diuretic group (P < 0.01 vs. pretreatment) and remained unchanged in losartan group (+0.06 +/- 0.43 mmol/L) and Hyzaar group (-0.04 +/- 0.44 mmol/L, all P > 0.05 vs. pretreatment).</p><p><b>CONCLUSION</b>Hyperuricacidemia prevalence was 25.83% and associated with higher BMI and abnormal renal function in examined EH patients. The low dose thiazide diuretics could further aggravate hyperuricacidemia and induce hypopotassemia while losartan could reduce hyperuricacidemia in EH patients.</p>

Two cases of hypokalemic rhabdomyolysis due to thiazide treatment / 대한내과학회지

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.

The Changes of Aquaporin-2 Expression in Rats with Lithium Induced Nephrogenic Diabetes Insipidus after Hydrochlorothiazide Administration / 대한신장학회잡지

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.

Clinical Studies on the Hypotensive Effect of Non-Thiazide Diuretics, Sulfamoyl Benzamide

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.