Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyponatremia is the commonest electrolyte abnormality in hospitalized patients and is associated with poor outcome. Hyponatremia is categorized on the basis of serum sodium into severe (< 120 mEq/L), moderate (120-129 mEq/L) and mild (130-134mEq/L) groups. Serum sodium has an important role in maintaining serum osmolality, which is maintained by the action of antidiuretic hormone (ADH) secreted from the posterior pituitary, and natriuretic peptides such as atrial natriuretic peptide and brain natriuretic peptide. These peptides act on kidney tubules via the renin angiotensin aldosterone system. Hyponatremia <120mEq/L or a rapid decline in serum sodium can result in neurological manifestations, ranging from confusion to coma and seizure. Cerebral salt wasting (CSW) and syndrome of inappropriate secretion of ADH (SIADH) are important causes of hyponatremia in tuberculosis meningitis (TBM). CSW is more common than SIADH. The differentiation between CSW and SIADH is important because treatment of one may be detrimental for the other; evidence of hypovolemia in CSW and euvolemia or hypervolemia in SIADH is used for differentiation. In addition, evidence of dehydration, polyuria, negative fluid balance as assessed by intake output chart, weight loss, laboratory evidence and sometimes central venous pressure are helpful in the diagnosis of these disorders. Volume contraction in CSW may be more protracted than hyponatremia and may contribute to border zone infarctions in TBM. Hyponatremia should be promptly and carefully treated by saline and oral salt, while 3% saline should be used in severe hyponatremia with coma and seizure. In refractory patients with hyponatremia, fludrocortisone helps in early normalization of serum sodium without affecting polyuria or functional outcome. In SIADH, V2 receptor antagonist conivaptan or tolvaptan may be used if the patient is not responding to fluid restriction. Fluid restriction in SIADH has not been found to be beneficial in TBM and should be avoided.
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PMID:Mechanism, spectrum, consequences and management of hyponatremia in tuberculous meningitis. 3273 4

Drug-drug interactions should be considered during the pharmacological treatment in patients with epilepsy and coexisting hypertension. Experimental studies in rodents showed that antihypertensive drugs which block the renin-angiotensin system (RAS) are able to decrease seizure severity. The anticonvulsant efficacy of several antiepileptic drugs (AEDs) was enhanced in different seizure models following concomitant treatment with RAS inhibitors. The current study examined the combined treatment with AEDs (carbamazepine, valproate, phenobarbital, clonazepam, ethosuximide, levetiracetam) and aliskiren, the first inhibitor of renin for treating hypertension, in the mouse 6 Hz psychomotor seizure model. The convulsive threshold was not affected by the renin inhibitor up to a dose of 75 mg/kg i.p. However, aliskiren (75 mg/kg) enhanced the anticonvulsant action of valproate reducing its ED50 value from 96.7 to 25.6 mg/kg (P < 0.01). The anticonvulsant potency of other AEDs was unaffected by aliskiren treatment. The combinations of aliskiren with AEDs did not cause adverse effects in mice evaluated in the rota-rod or passive avoidance task. Administration of the renin inhibitor did not significantly alter either plasma or brain concentration of valproate. The obtained results confirm earlier findings from other seizure tests (maximal electroshock and pentylenetetrazole-induced seizure test) that aliskiren has a neutral or positive effect on the anticonvulsant efficacy of AEDs, which suggest its safe use for the treatment of high blood pressure in patients with epilepsy. The beneficial anticonvulsant effect of the concomitant treatment with aliskiren and valproate is worthy of recommendation to further both preclinical and clinical studies.
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PMID:Effect of aliskiren on the anticonvulsant activity of antiepileptic drugs against 6 Hz-induced psychomotor seizures in mice. 3278 64

Temporal lobe epilepsy (TLE) is the most frequent type of epilepsy and is often refractory to pharmacological treatment. In this scenario, extensive research has identified components of the renin-angiotensin system (RAS) as potential therapeutic targets. Therefore, the aim of the present study was to evaluate the effects of long-term treatment with angiotensin-(1-7) [Ang-(1-7)] in male Wistar rats with TLE induced by pilocarpine (PILO). Rats with TLE were submitted to intracerebroventricular (icv) infusion of Ang-(1-7) (200 ng/kg/h) for 28 days, starting at the first spontaneous motor seizure (SMS). Body weight, food intake, and SMS were evaluated daily. Behavioral tests and hippocampal protein levels were also evaluated at the end of the treatment. Ang-(1-7) treatment reduced the frequency of SMS and attenuated low anxiety levels, increased locomotion/exploration, and reduced body weight gain that was induced by TLE. Moreover, Ang-(1-7) positively regulated the hippocampal levels of antioxidant protein catalase and antiapoptotic protein B-cell lymphoma 2 (Bcl-2), as well as mammalian target of rapamycin (mTOR) phosphorylation, which were reduced by TLE. The hippocampal up-regulation of angiotensin type 1 receptor induced by TLE was also attenuated by Ang-(1-7), while the Mas receptor (MasR) was down-regulated compared with epilepsy. These data show that Ang-(1-7) presents an antiepileptic effect, increasing neuroprotection markers and reducing SMS frequency, body weight, and behavior impairments found in TLE. Therefore, Ang-(1-7) is a promising coadjutant therapeutic option for the treatment of TLE.
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PMID:Antiepileptic effects of long-term intracerebroventricular infusion of angiotensin-(1-7) in an animal model of temporal lobe epilepsy. 3280 59


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