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)

We studied autonomic function in a 34-year-old woman who had episodes of catatonia, hypertension, and tachycardia. In one of these episodes, epinephrine and norepinephrine levels were extremely high. Catecholamine clearance was normal. Platelet alpha 2-adrenergic receptors were normal in number and affinity. Results of the phenylephrine infusion test suggested that these episodes were due to central activation of the sympathetic nervous system.
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PMID:Episodic catatonia, hypertension, and tachycardia: elevated plasma catecholamines. 401 Sep 46

A wealth of experimental evidence demonstrates that cerebral ischemia causes excessive release of glutamate and that glutamate contributes to ischemic injury. Glutamate antagonism by any of several mechanisms can ameliorate the extent of infarction. These antagonists comprise noncompetitive blockers of the ion channel associated with the N-methyl-D-aspartate (NMDA) receptor [e.g., aptiganel (Cerestat)], competitive antagonists of the glutamate recognition site of the NMDA receptor (e.g., selfotel) or of the glycine recognition site (e.g., ACEA 1021, GV150526), antagonists at the polyamine site (e.g., eliprodil), and drugs that may interfere with glutamate release by sodium channel blockade as well as having other actions (e.g., lubeluzole, 619C89). Clinical experience suggests that although some NMDA antagonists are poorly tolerated at putative neuroprotective doses (e.g., selfotel), potentially neuroprotective plasma concentrations can be achieved in humans with others (e.g., aptiganel), though tolerable adverse effects are frequently observed. These clinical effects include hypertension (which is probably preferable to the hypotension seen with nimodipine and lifarizine), sedation, confusion or hallucinations and, at high doses, catatonia. Glycine antagonists may be associated with fewer adverse effects, but preclinical studies suggest that brain penetration may be low. Although recent studies with selfotel and eliprodil have been discontinued because of insufficient evidence for a satisfactory risk/benefit ratio, encouraging experience with aptiganel, magnesium, and glycine antagonists has prompted continued clinical trials with these agents. To be of sufficient size to detect a clinically useful improvement in outcome, these trials need to be large (600-1,000 patients). Present trials with aptiganel (Cerestat) are comparing the efficacy and tolerability of two doses vs. placebo in patients treated within 6 hours of ischemic stroke. Outcome is assessed by the modified Rankin Scale at 3 months.
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PMID:Cerestat and other NMDA antagonists in ischemic stroke. 937 Nov 55

Catatonia is a large neuropsychiatric syndrome with multiple etiologies (psychiatric disorder, cerebral structural lesion, systemic disease, secondary to drugs and toxic agents) and varied clinical manifestations (cognitive and behavioral disorders, motor and speech disorders and vegetative disorders). The presence of disautonomy means a situation having vital risk, that requires immediate therapeutic intervention. A 22 year old woman was admitted due to a picture of stupor, fever, maintained postures, rigidity, seizures and tachycardia and hypertension episodes; this picture initiated four weeks earlier, with psychotic and affective symptoms and she slowly developed speech and motor activity impairment. Initially, she had been treated with neuroleptics, anticholinergics and antidepressants. The CT, MRI and CSF studies were normal. The EEG revealed diffuse slow waves and right frontotemporal paroxystic activity Laboratory determinations showed elevation of CK, coinciding with the vegetative disorder phase. The picture resolved progressively in two months, after receiving 19 sessions of electroshock therapy. In all the patients, and above all in those who receive neuroleptics, with symptoms suggesting catatonia, the presence of disautonomy should be considered as an alarm situation, which would make it necessary to discontinue the neuroleptics and to adopt special control. Electroshock therapy is the most effective therapeutic option in the situation of malignant catatonia.
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PMID:[Malignant catatonia as paradigm of neuropsychiatric disease]. 1261 Jul 60

The central neurotoxicity of cyclosporin A (CsA) has been abundantly documented in pediatric and adult recipients of bone marrow or organ transplants, with variations in the rate of occurrence from 0.5% to 35%. We report two cases of central neurotoxicity ascribable to CsA in children with nephrotic syndrome due to lipoid nephrosis. The manifestations of CsA-related central neurotoxicity include confusion, aphasia, dystonias, akinetic mutism, parkinsonism, palsies, seizures, catatonia, coma, brain hemorrhage, and cortical blindness. Decreased density of the cerebral white matter is visible by computed tomography (CT) in 50% of cases, with the most commonly involved sites being the occipital cortex, the cerebellum, the periventricular substance, and the brainstem. Magnetic resonance imaging is more sensitive and more specific than CT for investigating the white matter. High-signal lesions are seen on T2-weighted sequences in the areas that are abnormal by CT. Many risk factors have been reported, including hypomagnesemia, hypocholesterolemia, high-dose glucocorticoid therapy, arterial hypertension, and infections. We present two patients with central neurotoxicity both of whom have elevated cholesterol levels.
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PMID:Central neurotoxicity of cyclosporine in two children with nephrotic syndrome. 1475 27

The typical symptoms and signs of neuroleptic malignant syndrome (NMS) consist of fever muscle rigidity (stiffness, myoclonus, rod-like), alterations of consciousness (confusion, agitation, aggression, or catatonia), autonomic nervous system disturbances (i.e., hypertension, tachycardia, tachypnea, profuse sweating, and urine incontinence), abnormal blood tests such as low serum electrolytes, elevated serum creatinine phosphokinase (CPK) level, and leukocytosis. Muscle rigidity is often associated with myonecrosis, myoglobinuria, and elevated serum CPK. The mortality among NMS cases is in the 10 to 70% range depending on the severity of the symptoms and time of therapeutic approach. Mandatory therapy should include removal of causative agents, correction of body fluid and electrolytes, administration of benzodiazepine, clonazepam and bromocriptine (dopamine agonist), proved life-saving medications. The authors reported herein six cases with unusual clinical features of NMS. Four of them had been on antipsychotic for a year before becoming anorexic, dehydrated, agitated, and violent with paranoid delusion. One instance with underlying delirium tremens developed NMS after receiving haloperidol (30 mg IV) in addition to diazepam (200 mg IV) within 24 hours. Another patient was found to suffer from severe NMS after receiving bupropion (Dopamine inhibitor antidepressant) 300 mg/day. All patients displayed cardinal signs and symptoms of NMS in addition to dehydration and pallor. They were treated in the psychiatric ward and recovered rapidly from NMS after receiving clonazepam and bromocriptine and removal of the offending agents.
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PMID:Neuroleptic malignant syndrome: a review and report of six cases. 1721 72

Corticosteroids have been used since the 50s as anti-inflammatory and immunosuppressive drugs for the treatment of several pathologies such as asthma, allergy, rheumatoid arthritis, and dermatological disorders. Corticosteroids have three principal mechanisms of action: 1) inhibit the synthesis of inflammatory proteins blocking NF-kB, 2) induce the expression of anti-inflammatory proteins by IkB and MAPK phosphatase I, and 3) inhibit 5-lipoxygenase and cyclooxygenase-2. The efficacy of glucocorticoids in alleviating inflammatory disorders results from the pleiotropic effects of the glucocorticoid receptors on multiple signaling pathways. However, they have adverse effects: Growth retardation in children, immunosuppression, hypertension, hyperglycemia, inhibition of wound repair, osteoporosis, metabolic disturbances, glaucoma, and cataracts. Less is known about psychiatric or side effects on central nervous system, as catatonia, decreased concentration, agitation, insomnia, and abnormal behaviors, which are also often underestimated in clinical practice. The aim of this review is to highlight the correlation between the administration of corticosteroids and CNS adverse effects, giving a useful guide for prescribers including a more careful assessment of risk factors and encourage the use of safer doses of this class of drugs.
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PMID:Corticosteroid-related central nervous system side effects. 2434 92

Neuroleptic malignant syndrome (NMS) is associated with the administration of antipsychotic agents and other drugs such as l-dopa, antidepressants, and antihistaminic agents. Unexpected changes in mental status, new-onset catatonia, episodic tachycardia, tachypnea, hypertension, dysarthria, dysphagia, diaphoresis, sialorrhea, incontinence, low-grade temperature elevations, and rigidity should arouse suspicion. Several lines of evidence provide support for the involvement of dopamine. Most of the drugs implicated in NMS are D2 dopamine receptor antagonists. Central noradrenergic activity is also possibly related to the disorder, as sympathetic hyperactivity is associated with the active phase of NMS. Currently, the definitive role of GABA deficiency in NMS is yet to be established. Differential diagnosis should include malignant hyperthermia, lethal catatonia, lithium toxicity, serotonin syndrome, and heat stroke. A high degree of suspicion and the discontinuation of antipsychotic agents even if the diagnosis is not established are essential for the safety of the patient. Treatment of NMS should be individualized and be based empirically on the character, duration, and severity of the clinical signs and symptoms noted. The initial step in the treatment of NMS is the removal of the offending agent. Full-blown NMS is a serious condition and requires immediate supportive, nutritive, and electrolyte therapies. The administration of drugs that can improve NMS, such as IV dantrolene and/or oral bromocriptine, may also be taken into consideration, based on the severity and nature of the NMS.
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PMID:Neuroleptic malignant syndrome: risk factors, pathophysiology, and treatment. 2698 10

Identification of renin-angiotensin system in the interplay of hypertension and neurodegeneration has paved the way for the repurposing of antihypertensive drugs against Parkinsonism. Losartan carboxylic acid (LCA), the potent AT1 blocker metabolite of losartan, suffers from poor bioavailability and brain access. Since ascorbate transporters have earlier shown enough flexibility as carriers, we have conjugated losartan carboxylic acid to ascorbic acid with the aim of achieving higher oral/brain availability. Ester of LCA and ascorbic acid (FED) was developed keeping in view the substrate specificity of ascorbate transporters. Oral/brain bioavailability was assessed using in vivo pharmacokinetic model. Effect on central nervous system (CNS) and protection against Parkinsonism was evaluated using in vivo models. FED enhanced bioavailability of LCA. The higher brain availability of LCA enabled CNS protection as evident from the increase in locomotor activity, improved motor coordination, and protection against drug-induced catatonia. In conclusion, FED offers an approach to repurpose LCA against Parkinsonism. This can encourage further investigation to simultaneously address hypertension and neurodegeneration.
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PMID:Conjugation to Ascorbic Acid Enhances Brain Availability of Losartan Carboxylic Acid and Protects Against Parkinsonism in Rats. 3035 Feb 32