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)

Lithium is a monovalent cation that influences calcium metabolism in various tissues including the brain, kidney, heart, and parathyroid gland. Mr. A received treatment with lithium for 19 years because this medication proved to be effective in the management of his bipolar illness. However, he developed hypercalcemia, hypertension, and episodes of severe bradyarrhythmia (one of them requiring admission to the medical intensive care unit), with lithium levels within the therapeutic range. An extended endocrine workup showed hyperparathyroidism, with elevated serum parathyroid hormone levels, hypercalcemia, hypocalciuria, and normal serum phosphate levels. These biochemical findings are different from those of primary hyperparathyroidism and are attributed to direct actions of the lithium in the kidney. Discontinuation of the lithium did not result in reversal of the abnormal findings. The patient had surgery, and hyperplasia of the parathyroid gland was found. After parathyroidectomy, the bradyarrhythmia subsided and the patient showed improvement both in his psychiatric condition and hypertension. Preliminary observations in nine other lithium-induced hypercalcemic patients show a high frequency of arrhythmias with bradycardia and conduction defects. These findings suggest that hypercalcemia with lithium increases the risk of cardiac arrhythmia and emphasize the need for regular laboratory and electrocardiographic monitoring of patients on maintenance lithium therapy.
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PMID:Lithium therapy, hypercalcemia, and hyperparathyroidism. 1042 26

This report describes two cases of acute zolpidem overdose. The decedent in the first case was a 36-year-old female found dead in bed in her secured home. She had a history of psychiatric illness, including paranoid disorder, depression with panic episodes, and post-traumatic stress disorder. She was treated with risperidone and sertraline. Nine months prior to her death, the decedent was also prescribed zolpidem (Ambien). The postmortem examination revealed white foam within the larynx and upper trachea, which is indicative of pulmonary edema. Toxicological analyses of the urine showed the presence of caffeine, risperidone, and zolpidem. Subsequent quantitation of postmortem iliac serum revealed 5.6 microg/L of 9-hydroxyrisperidone and the following zolpidem concentrations: blood (subclavian), 4.5 mg/L; blood (iliac), 7.7 mg/L; vitreous humor, 1.6 mg/L; bile, 8.9 mg/L; urine, 1.2 mg/L; liver, 22.6 mg/kg; and gastric contents, 42 mg. The second case involved a 58-year old female, also found dead in bed, with white foam around her mouth. The decedent had a 25-year history of hypertension and mental illness--manic depression and schizophrenia. She was medicated with carbamazepine, naproxen, risperidone, and zolpidem. The postmortem examination revealed cardiomegaly, pulmonary edema, hepatomegaly, mild coronary atherosclerosis, and no signs of trauma. Toxicological analyses of the urine showed the presence of zolpidem and carbamazepine and metabolite. Zolpidem concentrations were as follows: blood (iliac), 1.6 mg/L; vitreous humor, 0.52 mg/L; bile, 2.6 mg/L; liver, 12 mg/kg; and gastric contents, 0.9 mg. The zolpidem blood concentrations of these cases are consistent with those of the previously published fatalities. The blood/vitreous humor ratios of zolpidem were 2.81 (subclavian) and 4.81 (iliac) in the first case and 3.08 (iliac) in the second case. These ratios, along with the sampling times of blood and vitreous humor for both cases, are not conclusive to indicate a definitive presence or absence of postmortem drug redistribution of zolpidem. The cause of death for both cases was determined to be acute zolpidem overdose, and manner of death was suicide.
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PMID:Acute zolpidem overdose--report of two cases. 1051 69

The pharmacotherapeutic use of lithium in the elderly as acute and maintenance therapy in bipolar disorder and augmentation therapy for major depression is well documented. Differences in the response to lithium are explained, in part, by the effect of age-related physiological changes, comorbid conditions, and concurrent medications on the pharmacokinetics of lithium in the elderly. The pharmacokinetic profile of lithium has been studied for many years, primarily in younger adult populations. Lithium pharmacokinetics may be influenced by a number of factors including age. It was first noted several years ago that elderly individuals required lower doses of lithium to achieve serum concentrations similar to those observed in younger adults. This is due to the combination of a reduced volume of distribution and reduced renal clearance. The composition of the human body changes with aging producing an increase in body fat, a decrease in fat-free mass and a decrease in total body water. Lithium clearance decreases as the glomerular filtration rate decreases with increasing age. The effects of other medical conditions in the elderly on the pharmacokinetics of lithium are less well delineated. Reduced lithium clearance is expected in patients with hypertension, congestive heart failure or renal dysfunction. Larger lithium maintenance doses are required in obese compared with non-obese patients. The most clinically significant pharmacokinetic drug interactions associated with lithium involve drugs which are commonly used in the elderly. Thiazide diuretics, ACE inhibitors, and nonsteroidal anti-inflammatory drugs can increase serum lithium concentrations. The tolerability of lithium is lower in the elderly. Neurotoxicity clearly occurs in the elderly at concentrations considered 'therapeutic' in general adult populations. There are no placebo-controlled randomised trials of lithium in old age and recommendations for clinical use are based on extrapolations from pharmacokinetic studies, anecdotal reports from mixed age populations and clinical experience in old age psychiatry. Serum concentrations of lithium need to be markedly reduced in the elderly population and particularly so in the very old and frail elderly.
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PMID:Differential pharmacokinetics of lithium in elderly patients. 1080 57

This study examines the clinical features, pathologic findings, and outcome of 24 patients with biopsy-proven lithium toxicity. The patient population was 50% male, 87.5% Caucasian, and had a mean age of 42.5 yr (range, 26 to 57). Mean duration of lithium therapy for bipolar disorder was 13.6 yr (range, 2 to 25). All patients were biopsied for renal insufficiency (mean serum creatinine 2.8 mg/dl; range, 1.3 to 8.0), with associated proteinuria >1.0 g/d in 41.7%. Nephrotic proteinuria (>3.0 g/d) was present in 25%. Other features included nephrogenic diabetes insipidus in 87% and hypertension in 33.3%. Renal biopsy revealed a chronic tubulointerstitial nephropathy in 100%, with associated cortical and medullary tubular cysts (62.5%) or dilatation (33.3%). All of the renal cysts stained for epithelial membrane antigen, while 51.4% stained with lectin Arachis hypogaea, and only 3.8% stained with Tetragonolobus purpureas, indicating they originated from distal and collecting tubules. The degree of tubular atrophy and interstitial fibrosis was graded as severe in 58.3%, moderate in 37.5%, and mild in 4.2% of cases. There was a surprisingly high prevalence of focal segmental glomerulosclerosis (50%) and global glomerulosclerosis (100%), sometimes of equivalent severity to the chronic tubulointerstitial disease. The significant degree of foot process effacement (mean 34%, five of 14 cases with >50%) suggests a potential direct glomerular toxicity. Focal segmental glomerulosclerosis correlated with proteinuria >1.0 g/d (P = 0.0014, Fisher exact test). Despite discontinuation of lithium, seven of nine patients with initial serum creatinine values >2.5 mg/dl progressed to end-stage renal disease (ESRD). Only three patients, all with initial serum creatinine <2.1 mg/dl, had subsequent improvement in renal function. By Kaplan-Meier survival analysis, the only significant predictor of progression to ESRD was serum creatinine >2.5 mg/dl at biopsy (P = 0. 008). In conclusion, lithium nephrotoxicity primarily targets distal and collecting tubules, with a higher incidence of proteinuria and associated glomerular pathology than recognized previously. Renal dysfunction is often irreversible despite lithium withdrawal, and early detection is essential to prevent progression to ESRD.
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PMID:Lithium nephrotoxicity: a progressive combined glomerular and tubulointerstitial nephropathy. 1090 57

We report the case of a 44 year old man who presented with a two-month history of dysarthria, ataxia and leg weakness whilst on maintenance lithium for bipolar disorder. Examination revealed significant cerebellar and pyramidal dysfunction. Serum lithium was 1.5 mmol/l, a moderate elevation above his usual stable levels of 0.4-0.8 mmol/l. The patient's past history included hypertension and chronic renal impairment and the development of neurological symptoms coincided with the recent onset of heart failure. On cessation of lithium he partially recovered, the main residuum being persistent cerebellar ataxia. The case is an example of lithium neurotoxicity developing insidiously in the absence of an overt acute phase syndrome, and highlights the need for keen observation of the patient in the hope of preventing permanent deficits.
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PMID:Lithium neurotoxicity: the development of irreversible neurological impairment despite standard monitoring of serum lithium levels. 1209 41

The purpose of this study is to assess the prevalence of mental illness in a university-based dental clinic population. Dentists routinely review the patient's medical history to identify any physical disease or condition that may impact dental treatment. Mental illness may also affect dental treatment and patient management. This study examined the degree to which patients seeking routine dental care report these diagnoses. Data was gathered from records of 508 consecutive new patients whose treatment plans were submitted for faculty approval. The patient's self-reported mental illness was obtained from the patient questionnaire and physical evaluation forms of the dental record. One hundred thirty-six patients (26.77 percent) reported at least one mental illness. Of all diseases and disorders recorded in the medical history, self-reported depression was second only to hypertension in frequency. Substance abuse, anxiety, anorexia, bulimia, insomnia, bipolar disorder, and post-traumatic stress disorder were also common findings. This study establishes the need for training of dental students to recognize and manage psychologically compromised patients. The dental curriculum must address these issues.
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PMID:Self-reported mental illness in a dental school clinic population. 1280 83

The presence of medical illnesses among inpatients with bipolar disorder is known to complicate treatment and lengthen hospital stay. However, except for a few specific diseases, little is known about prevalence of medical illnesses in bipolar outpatients and the effect it may have on treatment. The authors sought to assess the presence of medical illnesses in a large outpatient clinical sample of bipolar patients, and the effect that medical illnesses may have on the clinical assessment and treatment of the underlying bipolar disorder. Using the Duke University Medical Center clinical database, the authors categorized the medical diagnoses of 1379 patients who were treated with bipolar disorder from 2001 to 2002 through outpatient psychiatric clinics. The prevalence of medical comorbidities was examined, as well as the effect their presence had on the clinician's assessment of disease severity and time to improvement. As expected, medical comorbidities increased with age. The most common systemic illnesses in bipolar outpatients were Endocrine and Metabolic Diseases (13.6% of the sample), Diseases of the Circulatory System (13.0%), and Diseases of the Nervous System and Sense Organs (10.7%). Significant specific diseases included cardiovascular diseases/hypertension (10.7%), COPD/asthma (6.1%), diabetes (4.3%), HIV infection (2.8%), and hepatitis C infection (1.9%). Clinicians assessed greater severity of illness in patients with increasing numbers of comorbid conditions; however, the time to recovery was not significantly effected by the presence of medical comorbidity. In conclusion, comorbid medical illnesses are common in bipolar outpatients, increasing with age. HIV rates may be increased relative to population norms. Their presence compounds the severity of the illness at time of presentation.
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PMID:Medical comorbidity in a bipolar outpatient clinical population. 1553 92

Angiotensin-II, a product of angiotensin converting enzyme (ACE) action, regulates vascular tone, stimulates the release of pro-inflammatory cytokines, activates NFkappaB, increases oxidant stress, and suppresses nitric oxide synthesis. Thus, angiotensin-II is pro-inflammatory in nature. Hence, increase in ACE activity and the concentrations of angiotensin-II initiate and perpetuate inflammation. Since ACE is present in many tissues including: the uterus, placenta, vascular tissue, heart, brain, adrenal cortex and kidney, leukocytes, alveolar macrophages, peripheral monocytes, neuronal cells and epididymal cells, this suggests that angiotensin-II may have a role in atherosclerosis, congestive cardiac failure, stroke, bipolar disorder, schizophrenia, dementia, Alzheimer's disease, psoriasis, atopic and non-atopic dermatitis, eczema, several acute and chronic inflammatory diseases, and cancer, conditions in which inflammation is known to play a significant role. This suggests that ACE inhibitors and/or angiotensin-II receptor blockers could be of significant benefit in the management of these conditions. Alternatively, structural analogues of presently available ACE inhibitors and angiotensin-II receptor blockers could be developed such that they are not only useful in the treatment of hypertension and CHF but also possess anti-inflammatory actions.
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PMID:Is angiotensin-II an endogenous pro-inflammatory molecule? 1587 6

Recent clinical evidence indicates that the broad spectrum anticonvulsant drug lamotrigine is effective against the depressive phase of bipolar illness and the difficult to treat rapid cycling form of the disorder. However, the molecular mechanism underlying this therapeutic action remains uncertain. Given that inhibition of the A-type of monoamine oxidase (MAO) is a proven antidepressant mechanism, we investigated the effects of lamotrigine on MAO activities in vitro and on monoamine disposition in vivo. In vitro, lamotrigine inhibited rat brain MAO activities with Ki values (MAO-A, 15 microM; MAO-B, 18 microM) potentially within the therapeutic range for this drug. The effects of lamotrigine on the MAO-A activities of rat brain and human liver preparations were almost identical suggesting minimal species or tissue variation. In contrast, there was no (MAO-A) or minimal (MAO-B) reduction in brain MAO activities when assayed ex vivo following the administration of lamotrigine to rats. In vivo brain microdialysis failed to detect meaningful alterations in extracellular hippocampal or frontal cortex monoamine concentrations. Furthermore, lamotrigine did not modulate oral tyramine-induced hypertension in rats or 5-hydroxytryptophan-induced head shaking in mice, providing strong evidence that the drug does not perturb monoamine metabolism in vivo. The absence of observable effects of lamotrigine on monoamine disposition in vivo may be explained by the competitive and highly reversible nature of the interaction of lamotrigine with MAO isoforms. Thus, altered monoamine metabolism in vivo is unlikely to account for the antidepressant action of the drug in bipolar depression.
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PMID:Effect of lamotrigine on the activities of monoamine oxidases A and B in vitro and on monoamine disposition in vivo. 1612 25

Hypertension is predictive of a wide variety of subsequent adverse events in elderly patients, at least up to the age of 80 years. Treatment can reduce these adverse outcomes, although the benefits in the very elderly remain somewhat unclear. In the very elderly, there appears to be a reduction in cardiovascular events, but this reduction is perhaps at the expense of an increase in overall mortality. Target BPs in the elderly remain controversial. Among patients who have not had previous stroke or significant cardiovascular or renal disease, the benefits of reducing the SBP below 159 mm Hg are well documented. There is some evidence to suggest, however, that if doing so increases the day-night difference in BP by more than 20% or is associated with a decline in DBP below 65 mm Hg, then the benefits of treatment may be attenuated or lost. In addition, there is some suggestion that reducing SBP consistently below 135 mm Hg may accelerate cognitive decline. There appears to be a role for sodium restriction in those who can comply without otherwise compromising nutrient intake. Likewise, exercise may be beneficial and have benefits beyond simply lowering BP. Weight loss in those who are overweight may also help in lowering the BP. For most patients, low-dose thiazides such as hydrochlorothiazide are likely to be the appropriate first-line therapy (even in patients who have diabetes) unless they exacerbate or precipitate urinary incontinence or gout or complicate concomitant drug therapy (eg, lithium treatment of bipolar disorder). In very elderly patients, the apparent beneficial effects on strokes, major cardiovascular events, and heart failure rates may justify treating despite lack of benefit on overall mortality.
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PMID:Hypertension in the elderly. 1614 Jan 25


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