Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overactive bladder is associated with symptoms of urgency, with or without urge incontinence, usually with daytime frequency and nocturia in the absence of local pathological factors. Muscarinic receptor antagonists (antimuscarinics) are the first-line pharmacotherapy. Tolterodine, a competitive, nonselective antimuscarinic specifically developed for the treatment of overactive bladder, demonstrated tissue selectivity for the bladder over the parotid gland in an animal model. As of March 5, 2003, the immediate-release (IR) formulation had been approved in 72 countries and the extended-release (ER) formulation had been approved in 28 countries, and tolterodine had been administered to 5 million patients. This review evaluates the benefit-risk profile of tolterodine in the treatment of adults with overactive bladder, summarising clinical trial and postmarketing surveillance data. Tolterodine has been found to significantly reduce micturition frequency, urgency perception and the number of episodes of urge incontinence and increase the volume voided per micturition. Dry mouth, an antimuscarinic class effect, is the most commonly reported adverse effect but is mostly mild to moderate in severity. Serious adverse effects are reported infrequently. Based on summary and review of postmarketing surveillance and clinical trial safety data received by the market authorization holder and contained in the Periodic Safety Update Reports for tolterodine, several monitored serious events of the gastrointestinal tract (e.g. ileus or haemorrhage), nervous system (e.g. syncope, convulsions and memory disorders) and cardiovascular system (e.g. ventricular arrhythmia, atrial fibrillation, palpitations, bradycardia, transient ischaemic attacks and hypertension) were not considered related to tolterodine. QT or corrected QT (QTc) prolongation was not observed in any of the five cases of verified ventricular arrhythmia in patients administered tolterodine; there is insufficient evidence to indicate that tolterodine causes ventricular arrhythmia or extrasystoles or any specific type of cardiac rhythm abnormality. The safety profile of tolterodine is similar in patients aged > or =65 years and in younger adults. Clinically relevant drug interactions are limited to cytochrome P450 3A4 inhibitors, such as ketoconazole, and co-administration with such agents warrants a tolterodine dosage decrease. In addition, tolterodine IR 2mg twice daily is similar in efficacy to oxybutynin IR 5mg three times daily, and tolterodine ER 4 mg once daily is similar in efficacy to oxybutynin ER 10mg once daily. Dry mouth occurred less frequently with tolterodine than oxybutynin, and moderate to severe dry mouth occurred more than three times less frequently. Based on the low frequency of adverse events, the absence of unexpected adverse events and the very low frequency of serious adverse events, we conclude that tolterodine is a well tolerated treatment for overactive bladder in adults, in whom it should be considered as first-line therapy.
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PMID:Benefit-risk assessment of tolterodine in the treatment of overactive bladder in adults. 1547 9

Sleep apnoea syndrome is a well recognized entity. Sleep studies of diagnosed patients with sleep apnoea were analyzed to understand the clinical profiles of Nepalese patients with this disorder. Eighty nine patients were diagnosed to have sleep apnoea syndrome during the period of 15 months starting from November 2003. All these patients were subjected to a detailed clinical evaluation including symptoms, presence or absence of other risk factors and co-morbidities, general physical and systemic examination and relevant investigations before performing polysomnography. Clinical profiles of patients who were confirmed to have sleep apnoea syndrome with apnoea hypopnoea index (AHI) more than five were included in the study. Forty one patients (46.1%) were found to have mild disease (AHI 6-20), 22 patients (24.7%) had moderate disease (AHI 21-40) and 26 patients (29.2%) were found to have severe disease. The common symptoms were snoring, excessive daytime sleepiness, frequent awakenings, nocturia, and choking spells during sleep. Obesity was found to be the most important risk factor associated with sleep apnoea. Males having collar size more than 16 inches and females with collar size more than 14.5 inches were found to have an increased risk to develop this problem. Hypertension (66.3%), chronic obstructive pulmonary disease (43.2%) and cardiac diseases (19.1%) were the common co-morbidities associated with this disorder. Sleep apnoea syndrome is not an uncommon problem in Nepalese population. It could be the cause of various cardiovascular problems and may complicate patients with chronic obstructive pulmonary disease.
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PMID:Sleep apnoea syndrome in Nepal. 1629 18

Our aim was to assess the association between lower urinary tract symptoms (LUTS) and erectile dysfunction by means of International Prostate Symptom Score (IPSS) and Sexual Health Inventory for Men (SHIM) questionnaire. A total of 69 eligible patients who were admitted to our outpatient clinic with lower urinary tract symptoms were included in the study. A self administered questionnaire of IPSS and SHIM were given to patients. Demographics and medical history data were recorded. Any risk factor that may be associated with erectile dysfunction, including coronary artery disease, diabetes, hypertension, and smoking status, was determined in each patient. Correlation tests were used to examine the relationship between lower urinary tract symptoms and erectile dysfunction by controlling the effects of age and comorbidities. Mean age was 58.6 +/- 13.1 31-86 years. Mean SHIM and IPSS total score was 14.3 +/- 7.5 and 11.5 +/- 8.1, respectively. Spearman correlation coefficient between IPSS and SHIM scores was found to be -0.41. There was a significant negative correlation with IPSS total scores of moderate degree when both age and presence of risk factor was controlled (r = -0.31; p = 0.009). Storage symptom scores showed significant correlation with SHIM scores (r = -0.33; p = 0.000). The association between SHIM score and each item of IPSS showed significant correlation for urgency, straining and nocturia when age controlled. The degree of bother by LUTS as determined by the IPSS quality of life question was also correlated with SHIM scores; however, this correlation was not significant when age or risk factor for ED was controlled. The presence of LUTS especially storage symptoms is strongly associated with erectile dysfunction independent of age and comorbidities.
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PMID:Association between lower urinary tract symptoms and erectile dysfunction. 1657 95

The aim of this investigation was to evaluate the contribution of cephalometry to a statistical model integrating clinical, physical, and oximetric variables, to reduce demands for polysomnographies. Two hundred and twenty-five consecutive patients that had been referred to the sleep clinic for suspected obstructive sleep apnea (OSA) were studied. The clinical assessment of all patients consisted of a sleep related questionnaire, the Epworth sleepiness scale, and a physical examination. In addition, they all underwent spirometry, cephalometry, and a full polysomnography. The clinical variables related with OSA were questions concerning witnessing of apneas by bed partners, intensity of snoring, a history of hypertension, and nocturia. A significant relation was also found with score on the Epworth scale, sex, age, body mass index, neck and waist circumferences, total number and frequency of oxygen desaturations, and the lowest oxygen saturation value. Significant cephalometric measurements were: the linear distance from gonion to gnathion, from the hyoid bone to the mandibular plane, and from the posterior nasal spine to the tip of the soft palate, and the thickness of the uvula as well. A statistical model was built to estimate a patient's probability of having OSA based on clinical variables, physical examination, pulse oximetry, and cephalometry. The validation of this model demonstrated a remarkable ability in reducing the number of polysomnographic studies. We conclude that cephalometry combined with clinical variables, physical examination, and nocturnal oximetry is useful in the diagnosis of OSA and enables the sparing of a considerable number of polysomnographies.
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PMID:Usefulness of cephalometry in sparing polysomnography of patients with suspected obstructive sleep apnea. 1705 29

The aim of the study was to compare the incidence of obstructive sleep apnoea syndrome (OSAS) symptoms in relatives of subjects with OSAS and in relatives without OSAS but with clinical symptoms of this disease. The study group consisted of 186 relatives of patients with OSAS and 117 relatives of patients with symptoms of OSAS in whom the disease was not confirmed by polysomnography. They were all mailed a questionnaire with questions concerning anthropometric data, the presence of symptoms typical for OSAS and the presence of concomitant diseases. Analysis of the obtained data revealed an increased frequency of snoring, sleep apnea and nycturia in the relatives of patients with OSAS when compared to relatives of patients without OSAS, but the difference was not statistically significant. The incidence of daytime OSAS symptoms was significantly higher in the group of relatives of patients with OSAS. No differences in the incidence of arterial hypertension, ischaemic heart disease and diabetes mellitus were found.
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PMID:[Familial clustering of symptoms typical for OSAS]. 1717 78

Normal pressure hydrocephalus (NPH) is one of the few reversible causes of dementia in older adults and accounts for approximately 6% of all dementias. The cardinal sign of NPH is a hypokinetic gait disorder in which the older adult's feet look as though they are glued to the floor. The gait also has been described as magnetic. People with NPH also may have mild dementia and bladder and bowel incontinence. A 78-year-old man exhibited symptoms of NPH for at least 4 years before being diagnosed. A neurological assessment of the patient revealed gait, posture, and balance abnormalities; mild dementia; and urinary urgency, frequency, nocturia, and incontinence at least once a day. His risk factors for NPH included diabetes and hypertension. A computed tomography (CT) scan revealed dilated lateral ventricles in the brain. A lumbar puncture was used to remove 50 ml of cerebrospinal fluid, which resulted in a transient improvement in his gait for approximately 18 hours. A ventriculoperitoneal shunt was then inserted in the patient, and during a 1-year period his symptoms gradually improved. He recovered without any complications and was eventually able to resume his usual activities. When the gait associated with NPH is observed in an older adult, he or she should be referred to a neurologist or multidisciplinary team for a comprehensive evaluation. If an individual receives treatment for NPH, he or she may have an improved quality of life and the opportunity to reduce functional limitations and disability. Families may also experience positive outcomes, such as having a loved one who is cognitively improved and requires less care.
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PMID:Gait disorder is the cardinal sign of normal pressure hydrocephalus: a case study. 1759 8

1. The kidneys are the key organs to maintain the balance of the different electrolytes in the body and the acid-base balance. Progressive loss of kidney function results in a number of adaptive and compensatory renal and extrarenal changes that allow homeostasis to be maintained with glomerular filtration rates in the range of 10-25 ml/min. With glomerular filtration rates below 10 ml/min, there are almost always abnormalites in the body's internal environment with clinical repercussions. 2. Water Balance Disorders: In advanced chronic kidney disease (CKD), the range of urine osmolality progressively approaches plasma osmolality and becomes isostenuric. This manifests clinically as symptoms of nocturia and polyuria, especially in tubulointerstitial kidney diseases. Water overload will result in hyponatremia and a decrease in water intake will lead to hypernatremia. Routine analyses of serum Na levels should be performed in all patients with advanced CKD (Strength of Recommendation C). Except in edematous states, a daily fluid intake of 1.5-2 liters should be recommended (Strength of Recommendation C). Hyponatremia does not usually occur with glomerular filtration rates above 10 ml/min (Strength of Recommendation B). If it occurs, an excessive intake of free water should be considered or nonosmotic release of vasopressin by stimuli such as pain, anesthetics, hypoxemia or hypovolemia, or the use of diuretics. Hypernatremia is less frequent than hyponatremia in CKD. It can occur because of the provision of hypertonic parenteral solutions, or more frequently as a consequence of osmotic diuresis due to inadequate water intake during intercurrent disease, or in some circumstance that limits access to water (obtundation, immobility). 3. Sodium Balance Disorders: In CKD, fractional excretion of sodium increases so that absolute sodium excretion is not modified until glomerular filtration rates below 15 ml/min (Strength of Recommendation B). Total body content of sodium is the main determinant of extracellular volume and therefore disturbances in sodium balance will lead to clinical situations of volume depletion or overload: Volume depletion due to renal sodium loss occurs in abrupt restrictions of salt intake in advanced CKD. It occurs more frequently in certain tubulointerstitial kidney diseases (salt losing nephropathies). Volume overload due to sodium retention can occur with glomerular filtration rates below 25 ml/min and leads to edema, arterial hypertension and heart failure. The use of diuretics in volume overload in CKD is useful to force natriuresis (Strength of Recommendation B). Thiazides have little effect in advanced CKD. Loop diuretics are effective and should be used in higher than normal doses (Strength of Recommendation B). The combination of thiazides and loop diuretics can be useful in refractory cases (Strength of Recommendation B). Weight and volume should be monitored regularly in the hospitalized patient with CKD (Strength of Recommendation C). 4. Potassium Balance Disorders: In CKD, the ability of the kidneys to excrete potassium decreases proportionally to the loss of glomerular filtration. Stimulation of aldosterone and the increase in intestinal excretion of potassium are the main adaptive mechanisms to maintain potassium homeostasis until glomerular filtration rates of 10 ml/min. The main causes of hyperkalemia in CKD are the following: Use of drugs that alter the ability of the kidneys to excrete potassium: ACEIs, ARBs, NSAIDs, aldosterone antagonists, nonselective beta-blockers, heparin, trimetoprim, calcineurin inhibitors. Determination of serum potassium two weeks after the initiation of treatment with ACEIs/ARBs is recommended (Strength of Recommendation C). Routine use of aldosterone antagonists in advanced CKD is not recommended (Strength of Recommendation C). Abrupt reduction in glomerular filtration rate: Constipation. Prolonged fasting. Metabolic acidosis. A low-potassium diet is recommended with GFR less than 20 ml/min, or GFR less than 50 ml/min if drugs that raise serum potassium are taken (Strength of Recommendation C). In the absence of symptoms or electrocardiographic abnormalities, review of medications, restriction of dietary potassium and use of oral ion exchange resins are usually sufficient therapeutic measures (Strength of Recommendation C). If symptoms and/or electrocardiographic abnormalities are present, the usual parenteral pharmacological measures should be used (10% calcium gluconate, insulin and glucose, salbutamol, resins, diuretics) (Strength of Recommendation A). Parenteral bicarbonate and ion exchange resins in enemas are not recommended as first-line treatment (Strength of Recommendation C). Hemodialysis should be considered in patients with glomerular filtration rates below 10 ml/min (Strength of Recommendation C). 5. Acid-Base Disorders in CKD: Moderate metabolic acidosis (Bic 16-20) mEq/L is common with glomerular filtration rates below 20 ml/min, and favors bone demineralization due to the release of calcium and phosphate from the bone, chronic hyperventilation, and muscular weakness and atrophy. Its treatment consists of administration of sodium bicarbonate, usually orally (0.5-1 mEq/kg/day), with the goal of achieving a serum bicarbonate level of 22-24 mmol/L (Strength of Recommendation C). Limitation of daily protein intake to less than 1 g/kg/day is also useful (Strength of Recommendation C). Use of sevelamer as a phosphate binder aggravates metabolic acidosis since it favors endogenous acid production and therefore acidosis should be monitored and corrected if it occurs (Strength of Recommendation C). Hypocalcemia should always be corrected before metabolic acidosis in CKD (Strength of Recommendation B). Metabolic acidosis is an infrequent disorder and requires exogenous alkali administration (bicarbonate, phosphate binders) or vomiting.
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PMID:[Electrolyte and acid-base balance disorders in advanced chronic kidney disease]. 1901 44

OBJECTIVES To evaluate the number of medical and urological conditions associated with nocturia in a cohort of older men who were primary-care enrolees, and to assess the feasibility and efficacy of using a multicomponent intervention to reduce nocturia and its bother. SUBJECTS AND METHODS Men aged > or =50 years and with two or more episodes of nocturia were recruited from the primary-care clinics at one Veterans Affairs Medical Center to participate in a 4-week, open-label, prospective pilot study. A multicomponent intervention composed of behavioural therapy and targeted drug therapy was administered according to a specified protocol based upon identified risk factors for nocturia. Outcome measures included self-reported nocturia and bother on the American Urological Association (AUA)-7 Symptom Index, 3-day bladder diaries and self-reported sleep-related measures recorded using 7-day sleep diaries. RESULTS Fifty-five men completed the protocol (mean age 67 years, sd 8.3); they had a mean of 4.5 of nine defined conditions potentially related to nocturia. Highly prevalent conditions included moderate-to-severe benign prostatic hyperplasia (87%), hypertension (86%) and urinary frequency (71%). The mean diary-recorded nocturia decreased from 2.6 to 1.9 (P < 0.001), and bother score reduced from 3.1 to 1.1, representing a change from a 'medium' to a 'very small' problem (on a 5-point scale). Sleep diary-derived measures also improved significantly (time to initiate sleep, time to return to sleep after awakening, quality of sleep). CONCLUSIONS Given that individual older patients often have multiple coexistent risk factors for nocturia, identifying a principal cause of nocturia, a concept emphasized in treatment guidelines, proved to be difficult. Implementing a multicomponent behavioural intervention combined with drug(s) was feasible in older men and reduced nocturia frequency, bother from nocturia, and time to initiate sleep, within 4 weeks. These promising results merit repeating using a randomized, controlled trial.
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PMID:A multicomponent behavioural and drug intervention for nocturia in elderly men: rationale and pilot results. 1922 Feb 47

Patients with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTSs) have a considerably higher prevalence of cardiovascular disease (CVD) than the general population in old age. Many hypotheses have been created to explain traditional clinical risk factors of CVD, including age, male gender, cigarette smoking, inheritance, high blood pressure (BP), obesity, elevated fasting plasma glucose, diabetes mellitus, dyslipidemia, decreased physical activity and metabolic syndrome; or nontraditional risk factors such as oxidative stress, inflammation, vascular calcification, malnutrition, homocysteine and genetic variation. Although these risk factors are important in CVD pathophysiology and clinical presentation, there is still no single theory sufficient to provide an adequate explanation for all the properties of CVD. We speculate that by causing nocturia-induced sleep disturbances, BP variability, increased sympathetic activity, non-dipping BP variations; BPH may be an insidious risk factor for CVD. Benign prostate hyperplasia may be related to increased BP, coronary ischemic hearth disease or other cardiovascular pathologic conditions. This attention on BPH may produce a new approach to the diagnosis and treatment of CVD. Although the underlying mechanisms are still exactly unclear, further prospective randomized controlled studies are needed to identify if patients with BPH/LUTS is higher risk for CVD.
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PMID:An insidious risk factor for cardiovascular disease: benign prostatic hyperplasia. 1935 54

Patients with chronic kidney disease have less than expected decline in blood pressure during sleep (nondipping) and commonly experience the vexing symptom of nocturia. To better understand the relationship among nocturia, nighttime physical activity, and nondipping, we studied 98 patients with chronic kidney disease on 2 occasions, 1 month apart, with 24-hour ambulatory blood pressure monitoring and simultaneous activity monitoring with wrist actigraphy. Patients with nocturia had greater actigraphically recorded nighttime physical activity compared to those with no nocturia. The drop in activity from wake to sleep was reduced to a similar extent whether the patients had nocturia once or twice, but patients who had nocturia >/=3 times had the least reduction from wake to sleep activity (P<0.001 versus those with less degrees of nocturia). Those with nocturia had a lesser drop in systolic ambulatory blood pressure during sleep compared with those without nocturia. The average fall in sleep systolic blood pressure was 9.8 mm Hg (95% CI: 8.0 to 11.6 mm Hg) in those without nocturia compared with 3.4 mm Hg (95% CI: 2.7 to 4.1 mm Hg) in those with any severity of nocturia (P<0.001 for difference). Nondipping in patients with nocturia was mediated by nighttime physical activity. These differences were independent of estimated glomerular filtration rate, albuminuria, or use of diuretics. Thus, nocturia, which may reflect impaired renal tubular function, is associated with nondipping in patients with chronic kidney disease and appears to be mediated by increased nocturnal activity. Whether nocturia itself or the resulting nondipping associated with nocturia is of prognostic importance for cardiorenal events in patients with chronic kidney disease should be tested in future studies.
Hypertension 2009 Sep
PMID:Nocturia, nocturnal activity, and nondipping. 1984 Dec 82


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