UMLS:C0020538 - FACTA Search

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Query: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiovascular disease is claimed to be one of the most severe complications of acromegaly, contributing significantly to mortality in this disease. In fact, an excess of growth hormone (GH) and insulin-like growth factor 1 (IGF-I) causes a specific derangement of cardiomyocytes, leading to abnormalities in cardiac muscle structure and function, inducing a specific cardiomyopathy. In the early phase of acromegaly the excess of GH and IGF-I induces a hyperkinetic syndrome, characterized by increased heart rate and increased systolic output. Concentric hypertrophy is the most common feature of cardiac involvement in acromegaly, found in more than two thirds of patients at diagnosis. This abnormality is commonly associated with diastolic dysfunction and eventually with impaired systolic function ending in heart failure, if the GH/IGF-I excess is left untreated. In addition, abnormalities of cardiac rhythm and of heart valves have also been described in acromegaly. The coexistence of other complications, such as arterial hypertension and diabetes mellitus, aggravates acromegalic cardiomyopathy. Successful control of acromegaly induces a decrease in left ventricular mass and an improvement in diastolic function, while the effects of GH/IGF-I suppression on systolic function are more variable. However, since cardiovascular alterations in young patients with short disease duration are milder than in those with longer disease duration, it is likely to be easier to reverse and/or arrest acromegalic cardiomyopathy in young patients with early-onset disease. In conclusion, careful assessments of cardiac function, morphology, and activity are required in patients with acromegaly. An early diagnosis and prompt effective treatment are important in order to reverse acromegalic cardiomyopathy.
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PMID:Cardiac abnormalities in acromegaly. Pathophysiology and implications for management. 1533 Jun 78

The aim of this study was to characterize a newly developed clonidine transdermal patch, KBD-transdermal therapeutic system (TTS), for the treatment of attention deficit hyperactivity disorder in children. In vitro release, penetration, and in vivo pharmacokinetics in rabbits were investigated. The smaller size of KBD-TTS (2.5 mg/2.5 cm2) showed a similar in vitro penetration to those of Catapres-TTS (2.5 mg/3.5 cm2, a clonidine transdermal patch used for the treatment of hypertension, Alza Corporation, U.S.A.). The transdermal penetration rate of clonidine was mainly controlled by the ethylene vinylacetate membrane used in the patch. The skin layer may be only a minor rate-limiting barrier after the topical skin layer at the dosing site is saturated with penetrating clonidine in the initial phase (0 to 12 h). A sensitive liquid chromatography-mass spectrometry method for the quantification of clonidine in rabbit plasma was developed using solid-phase extraction and gradient elution on LC combined with the selected-ion monitoring (SIM) mode. A single dose of clonidine transdermal patch (KBD-TTS) or Catapres-TTS was transdermally administered to rabbits (n=6 each) and removed after 168 h. The average half-life, Tmax, Cmax and Css values of clonidine in rabbits following administration of KBD-TTS were 19.27+/-4.68 h, 52.56+/-25.77 h, 27.39+/-9.03 ng/ml, and 25.82+/-9.34 ng/ml, similar to those of Catapres-TTS, respectively. The clonidine plasma concentration of KBD-TTS reached a steady state at 24 h through 168 h. The in vitro release rate of the clonidine from KBD-TTS significantly correlated with the in vivo absorption rate (p<0.001).
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PMID:In vitro and in vivo characterization of a newly developed clonidine transdermal patch for treatment of attention deficit hyperactivity disorder in children. 1568 89

The spontaneously hypertensive rat (SHR) is generally considered to be a suitable genetic model for the study of attention deficit hyperactivity disorder (ADHD), since it displays hyperactivity, impulsivity, poorly sustained attention, and deficits in learning and memory processes. Converging evidence suggests a primary role of disturbance in the dopaminergic neurotransmission in ADHD patients and in SHR, and in addition, some studies have also demonstrated alterations in adenosinergic neurotransmission in SHR. In the present study, adult female Wistar (WIS) and SHR rats received caffeine (1-10 mg/kg i.p.) 30 min before training, immediately after training, or 30 min before a test session in the spatial version of the Morris water maze. The effect of caffeine administration on WIS and SHR blood pressure was also measured. SHR needed significantly more trials in the training session to acquire the spatial information, but they displayed a similar profile to that of WIS rats in the test session (48 h later), demonstrating a selective deficit in spatial learning. Pre-training administration of caffeine (1-10 mg/kg i.p.) improved this spatial learning deficit in SHR, but did not alter the WIS performance. In contrast, post-training administration of caffeine (3 mg/kg i.p.) did not alter the SHR test performance, but increased memory retention in WIS rats. No dose of caffeine tested altered the mean blood pressure of WIS or SHR. These results demonstrate a selective spatial learning deficit in SHR which can be attenuated by pre-training administration of caffeine. In addition, the present findings indicate that the spatial learning deficit in SHR is not directly related to hypertension.
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PMID:Caffeine improves spatial learning deficits in an animal model of attention deficit hyperactivity disorder (ADHD) -- the spontaneously hypertensive rat (SHR). 1587 34

Spontaneously hypertensive rats (SHRs) are often used as a model of attention deficit hyperactivity disorder (ADHD) and to investigate the effects of hypertension on cognitive function. Further, they appear to have reduced numbers of central nicotinic acetylcholine receptors (nAChRs) and, therefore, may be useful to model certain aspects of Alzheimer's disease (AD) and other forms of dementia given that a decrease in nAChRs is thought to contribute to cognitive decline in these disorders. In the present study, based on reports that chronic nicotine exposure increases nAChRs in several mammalian models, we tested the hypothesis that repeated exposures to a relatively low dose of the alkaloid would ameliorate the receptor deficits in SHR. Thus, young-adult SHRs and age-matched Wistar-Kyoto (WKY) control rats were treated with either saline or nicotine twice a day for 14 days (total daily dose = 0.7 mg/kg nicotine base) and then sacrificed. Quantitative receptor autoradiography with [125I]-IPH, an epibatidine analog, revealed: (1) that high-affinity nAChRs were higher in saline-treated WKY (control) rats compared to saline-treated SHRs in 18 of the 19 brain region measured, although statistically different only in the mediodorsal thalamic nuclei, (2) that nicotine significantly increased nAChR binding in WKY rats in six brain areas including cortical regions and the anterior thalamic nucleus, (3) that there were no cases where nicotine significantly increased nAChR binding in SHRs. These results indicate that subjects deficient in nAChRs may be less sensitive to nAChR upregulation with nicotine than normal subjects and require higher doses or longer periods of exposure.
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PMID:Effect of repeated nicotine exposure on high-affinity nicotinic acetylcholine receptor density in spontaneously hypertensive rats. 1591 Nov 41

The cloning of multiple subtypes of both alpha1- and alpha2-adrenoceptors has renewed interest in the therapeutic application of agents interacting with these receptors. Effort has primarily been directed towards the design of uroselective alpha1-adrenoceptor antagonists for the treatment of benign prostatic hyperplasia (BPH). Evidence is accumulating for the involvement of a novel alpha1-adrenoceptor, designated as alpha1L-adrenoceptor, in alpha1-adrenoceptor-mediated smooth muscle contraction in prostatic and other urogenital tissues. While several antagonists showing a high degree of uroselectivity in animal models have been identified, their clinical superiority over the currently available alpha1-adrenoceptor antagonists has not yet been demonstrated. It is possible that the interaction with alpha1-adrenoceptors, as yet uncharacterised subtypes, at non-prostatic sites contributes to the therapeutic activity of this drug class in BPH. The alpha1-adrenoceptor subtypes involved in the control of vascular tone are currently being evaluated, and the profile of interaction with the various alpha1-adrenoceptor subtypes may play a key role in the efficacy of cardiovascular drugs such as carvedilol. Alpha2-adrenoceptor agonists are now being employed for a variety of therapeutic applications, most involving actions on receptors within the central nervous system (CNS). These agents are useful in the treatment of hypertension, glaucoma, opiate withdrawal and attention deficit hyperactivity disorder (ADHD), and as analgesics and adjuncts to general anaesthesia. While subtype selectivity has not yet been applied to the design of new alpha2-adrenoceptor agonists for these applications, recent gene mutation/knock-out experiments have identified the alpha2-subtypes involved in some of these actions, and optimisation of a therapeutic profile may be possible. Furthermore, the design of agents combining affinities for multiple adrenoceptor subtypes, or the combination of a specific adrenoceptor affinity profile with another pharmacological action, may offer advantages over molecules selective for an individual adrenoceptor subtype.
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PMID:Recent advances in the identification of alpha1- and alpha2-adrenoceptor subtypes: therapeutic implications. 1598 5

Acromegaly is characterized by an increased cardiovascular morbidity and mortality. In fact, growth hormone and insulin-like growth factor-I excess induces a specific cardiomyopathy. The heart is involved from the very early stages of the disease in which the hyperkinetic syndrome (high heart rate and increased systolic output) takes place. Frequently, if the disease is untreated for many years or unsuccessfully treated, concentric biventricular hypertrophy and diastolic dysfunction can develop and, at least, lead to diastolic congestive heart failure. Rhythm disturbances and valve dysfunction are also frequently described in acromegaly. The coexistence of other complications, such as diabetes and arterial hypertension, can induce the worsening of acromegalic cardiomyopathy. Control of acromegaly by surgery or pharmacotherapy could improve cardiovascular morbidity thanks to decreasing left ventricular mass and reducing cardiac dysfunction. In conclusion, an early diagnosis and a careful evaluation of cardiac function, morphology and activity seem to be mandatory in acromegaly.
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PMID:Acromegaly and the cardiovascular system. 1704 85

Convincing healthy people that they are sick and require medicines can enormously expand the market. Disease mongering can turn ordinary ailments like baldness into medical problems, consider risk factors such as hypertension and osteoporosis as diseases and frame prevalence estimates to increase potential markets. In Asia, conditions like erectile dysfunction, male pattern baldness, attention deficit hyperactivity disorder and irritable bowel syndrome, and the drugs to treat them, are widely promoted. Fairness creams and traditional medicines are also widely used. The cost of disease mongering to the individual and the community is expected to be high. Some authors have argued that medicalisation of illnesses may not be a problem and the real problem may be the lack of medicines. Doctors will play a key role in combating disease mongering. Disentanglement from the pharmaceutical industry and development of a capacity for critical analysis are required. Educating patients and empowering them to make decisions are important. Several initiatives have been undertaken to combat disease mongering. Initiatives at the level of the patient and the physician are especially important. Studies on the extent and knowledge of disease mongering among doctors and medical students, and their economic and social consequences are urgently required.
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PMID:Disease mongering. 1912 61

Two patients with pheochromocytoma initially presented with behavioral symptoms similar to those seen with attention deficit hyperactivity disorder (ADHD): inability to concentrate, hyperactivity, and poor school performance. One patient was treated with dextroamphetamine/amphetamine for 4 months, at which time medication was discontinued when hypertension appeared. The second patient had hypertension when initially seen. All behavioral abnormalities resolved following tumor resection. Children with ADHD-like symptoms who present atypically at an older age or have other somatic signs and symptoms such as headaches and hypertension should undergo evaluation to rule out an organic etiology.
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PMID:Two cases of pheochromocytoma presenting with ADHD (attention deficit hyperactivity disorder)-like symptoms. 1797 24

Modafinil is a wake-promoting agent that is pharmacologically different from other stimulants. It has been investigated in healthy volunteers, and in individuals with clinical disorders associated with excessive sleepiness, fatigue, impaired cognition and other symptoms. This review examines the use of modafinil in clinical practice based on the results of randomized, double-blind, placebo-controlled clinical trials available in the English language in the MEDLINE database. In sleep-deprived individuals, modafinil improves mood, fatigue, sleepiness and cognition to a similar extent as caffeine but has a longer duration of action. Evidence for improved cognition in non-sleep-deprived healthy volunteers is controversial.Modafinil improves excessive sleepiness and illness severity in all three disorders for which it has been approved by the US FDA, i.e. narcolepsy, shift-work sleep disorder and obstructive sleep apnoea with residual excessive sleepiness despite optimal use of continuous positive airway pressure (CPAP). However, its effects on safety on the job and on morbidities associated with these disorders have not been ascertained. Continued use of CPAP in obstructive sleep apnoea is essential. Modafinil does not benefit cataplexy.In very small, short-term trials, modafinil improved excessive sleepiness in patients with myotonic dystrophy. It was efficacious in fairly large studies of attention deficit hyperactivity disorder (ADHD) in children and adolescents, and was as efficacious as methylphenidate in a small trial, but has not been approved by the FDA, in part because of its serious dermatological toxicity. In a trial of 21 non-concurrent subjects, with 2-week treatment periods, modafinil was as effective as dexamfetamine in adult ADHD. Modafinil was helpful for depressive symptoms in bipolar disorder in a trial that excluded patients with stimulant-induced mania. A single dose of modafinil may hasten recovery from general anaesthesia after day surgery. A single dose of modafinil improved the ability of emergency room physicians to attend didactic lectures after a night shift, but did not improve their ability to drive home and caused sleep disturbances subsequently.Modafinil had a substantial placebo effect on outcomes such as fatigue, excessive sleepiness and depression in patients with traumatic brain injury, major depressive disorder, schizophrenia, post-polio fatigue and multiple sclerosis; however, it did not provide any benefit greater than placebo.Trials of modafinil for excessive sleepiness in Parkinson's disease, cocaine addiction and cognition in chronic fatigue syndrome provided inconsistent results; all studies had extremely small sample sizes. Modafinil cannot be recommended for these conditions until definitive data become available.Modafinil induces and inhibits several cytochrome P450 isoenzymes and has the potential for interacting with drugs from all classes. The modafinil dose should be reduced in the elderly and in patients with hepatic disease. Caution is needed in patients with severe renal insufficiency because of substantial increases in levels of modafinil acid. Common adverse events with modafinil include insomnia, headache, nausea, nervousness and hypertension. Decreased appetite, weight loss and serious dermatological have been reported with greater frequency in children and adolescents, probably due to the higher doses (based on bodyweight) used. Modafinil may have some abuse/addictive potential although no cases have been reported to date.
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PMID:Approved and investigational uses of modafinil : an evidence-based review. 1872 34

ABSTRACT The pertinent literature was reviewed on cardiovascular changes induced by psychostimulant medication treatment of hyperactive children. An assessment of 15 controlled studies using test doses of methylphenidate revealed a significant elevation of the resting heart rate in previously unmedicated children (mean + 11 beats/min) but, with continued drug treatment, only a minor insignificant increase (mean + 4 BPM) is observed. Methylphenidate resulted in no consistent or clinically meaningful blood pressure changes (8 studies) and no EKG irregularities (4 studies). Available data for dextroamphetamine and pemoline were less extensive, but showed essentially no significant cardiovascular changes in hyperactive youth. Stimulant overdoses in nonhyperactive children often led to hypertension and tachycardia, but were associated with only one cardiovascular fatality (amphetamine). Comparable studies of these stimulants in adults revealed: (1) tachycardia and hypertension following high test doses of methylphenidate, (2) hypertension but no tachycardia following high test doses of dextroamphetamine, (3) far greater cardiovascular changes following the parenteral administration of stimulants, (4) the development of a prominent degree of tolerance to the cardiovascular effects of stimulants with continued use, (5) very infrequent cardiovascular changes (3%) in medically ill, older adults following stimulant treatment for depression, and (6) infrequent cardiomyopathy and arteritis in association with amphetamine abuse, but not with pemoline or methylphenidate use. The stimulant-induced changes in children are modest in comparison with changes in cardiovascular functioning associated with normal daily activities, and are not comparable to the risks that can occur with tricyclic antidepressants. There appears to be a wide margin of cardiovascular safety when standard psychostimulants are taken orally in customary doses for long periods by hyperactive children. In view of the numerous negative studies, it probably is not essential to monitor heart rate, blood pressure, or EKG prior to or during routine psychostimulant treatment of children and adolescents with ADHD, unless there are comorbid cardiovascular abnormalities.
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PMID:Relative cardiovascular safety of psychostimulants used to treat attention-deficit hyperactivity disorder. 1963 Jun 10

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