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)

We report a case of a 10-year-old boy, being treated for seizures with carbamazepine, who developed acute liver failure within four days of initiation of therapy for suspected tuberculosis with isoniazid, rifampin, pyrazinamide, and ethambutol. Isoniazid-induced liver disease was diagnosed. The likely role of carbamazepine and rifampin in potentiating the hepatotoxicity of isoniazid, and the importance of early recognition of isoniazid-induced liver disease, are discussed.
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PMID:Acute liver failure caused by isoniazid in a child receiving carbamazepine. 966 30

This study tests the hypothesis that glutamate receptors are altered in the brains of alcoholics as a result of chronic alcohol neurotoxicity. Excessive release of the excitatory neurotransmitter glutamate may damage postsynaptic neurons by increasing calcium flux through N-methyl-D-aspartate (NMDA) receptor-gated ion channels. Alcohol has opposite effects on the NMDA receptor, depending on the duration of exposure. Acute exposure to alcohol inhibits ion flow through NMDA receptors, whereas chronic exposure upregulates the number of these receptors and thereby increases ion flow. Acute withdrawal from alcohol results in hyperexcitability and seizures in the presence of upregulated NMDA receptors, making postsynaptic neurons vulnerable to excitotoxic damage. For this study, 13 grossly and histologically normal brains from alcoholics and 13 brains from nonalcoholic controls were selected from our brain bank. The two groups were matched for age, postmortem interval, and storage time. Maximal binding and affinities of NMDA receptors were determined by quantitative autoradiography in the cingulate cortex, the cornu Ammonis of the hippocampus, and in the cerebellar vermis. Binding was determined with an agonist, L-[3H]glutamate, with a competitive antagonist, [3H]CGP-39653, and with an antagonist binding in the channel interior, [3H]MK-801. No significant differences were found in receptor densities or affinities between alcoholics and controls. Real differences were not likely to be obscured by nonalcohol-related variables because the groups were closely matched for age, autopsy delay, time in storage, and central nervous system medications. Various diseases causing acute and chronic hypoxia did not significantly affect receptor density or affinity. Liver diseases and thiamine deficiency were excluded. A long-lasting upregulation of the number or affinity of NMDA receptors is not a key feature of chronic alcoholics.
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PMID:Glutamate receptors in the cingulate cortex, hippocampus, and cerebellar vermis of alcoholics. 1002 96

The aim of this study was to evaluate the hypothetical role of kindling phenomenon in the development and course of alcohol withdrawal (AW) seizures and delirium tremens (DT). The 2186 medical records of 1179 patients hospitalized in Nowowiejski Hospital in Warsaw from 1973 to 1987 were reviewed using a structured questionnaire. Investigating the role of kindling, a course of consecutive AW episodes of patients hospitalized several times was analyzed. The relationships of withdrawal seizures with the duration of alcohol abuse, the number of prior detoxification episodes, and other variables were also studied. Increasing severity of AW symptoms was observed during the course of consecutive episodes in 22.5% of patients. The first episode of DT was preceded by withdrawal seizures in 11% of cases. First-ever withdrawal seizures occurred more frequently in patients with head injury in the past and with coexisting symptoms of alcohol liver disease. Occurrence of withdrawal seizures and DTs did not correlate with the number of previous withdrawal episodes or with the length of period of intensive drinking. We concluded that the kindling model could be applied only to some cases in the development of AW seizures and DTs. Kindling should be considered as one of the multiple mechanisms involved in the pathogenesis of AW delirium.
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PMID:Assessment of the role of kindling in the pathogenesis of alcohol withdrawal seizures and delirium tremens. 1006 46

Although heavy alcohol intake is known to be one of the most common causative factors of liver disease, pancreatitis, upper gastrointestinal and neurological disorders, the influence of the drinking pattern is largely unknown. The study investigated the relationship of alcohol-related medical disorders in alcoholics and their drinking pattern. Two hundred and forty-one chronic alcoholics were referred consecutively for detoxification and their drinking pattern was sufficient for them to be included in this study. History of alcohol abuse as well as drinking behaviour in the last 6 months were assessed by a semi-structured interview. Findings included intensive clinical examination with abdominal ultrasound in most subjects. Heavy drinking with frequent inebriation was most often found in our sample (44.4%), whereas continuous heavy alcohol consumption without intoxication (33.6%), and an episodic drinking style (22.0%) were less frequent. The heavy drinkers suffered more often from pancreatitis, oesophageal varices, polyneuropathy or erectile dysfunction than episodic drinkers. They also showed more upper gastrointestinal disorders, although the estimated life-time alcohol intake was comparable to continuous drinkers. No difference relating to withdrawal delirium or seizures could be found between the groups of alcoholics. Frequent heavy drinkers showed a trend to more alcohol-related medical disorders than alcoholics with a different drinking pattern, although they were younger and their estimated life-time alcohol intake was comparable to that of continuous drinkers. Thus, the drinking pattern, particularly frequent inebriation, has an influence on the occurrence of alcohol-related disorders.
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PMID:Drinking pattern and alcohol-related medical disorders. 1041 7

The liver is the major site of biotransformation for most opioids. Thus, the disposition of these drugs may be affected in patients with liver insufficiency. The major metabolic pathway for most opioids is oxidation. The exceptions are morphine and buprenorphine, which primarily undergo glucuronidation, and remifentanil, which is cleared by ester hydrolysis. Oxidation of opioids is reduced in patients with hepatic cirrhosis, resulting in decreased drug clearance [for pethidine (meperidine), dextropropoxyphene, pentazocine, tramadol and alfentanil] and/or increased oral bioavailability caused by a reduced first-pass metabolism (for pethidine, dextropropoxyphene, pentazocine and dihydrocodeine). Although glucuronidation is thought to be less affected in liver cirrhosis, and clearance of morphine was found to be decreased and oral bioavailability increased. The consequence of reduced drug metabolism is the risk of accumulation in the body, especially with repeated administration. Lower doses or longer administration intervals should be used to remedy this risk. Special risks are known for pethidine, with the potential for the accumulation of norpethidine, a metabolite that can cause seizures, and for dextropropoxyphene, for which several cases of hepatotoxicity have been reported. On the other hand, the analgesic activity of codeine and tilidine depends on transformation into the active metabolites, morphine and nortilidine, respectively. If metabolism is decreased in patients with chronic liver disease, the analgesic action of these drugs may be compromised. Finally, the disposition of a few opioids, such as fentanyl, sufentanil and remifentanil, appears to be unaffected in liver disease.
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PMID:Pharmacokinetics of opioids in liver disease. 1045 81

Carbohydrate-deficient glycoprotein syndrome (CDGS) is a newly delineated group of inherited multisystemic disorders associated with abnormal glycosylation of a number of serum glycoproteins. Several types have been described on the basis of clinical presentation and biochemical changes of the glycosylation of serum transferrin and attributed to different enzymatic defects; their clinical presentations are fully different and a clinical heterogeneity is observed within a same type of CDGS. Patients with CDGS type la usually present with neurologic (hypotonia, strabismus and cerebellar hypoplasia) and cutaneous (inverted nipples, abnormal distribution of adipose tissue) abnormalities, together with multivisceral involvement (digestive, hepatic, cardiac, renal). However, neurologic and cutaneous symptoms may be absent, so that CDGS must be looked for in case of unexplained organ failure such as isolated liver insufficiency, cardiomyopathy, pericarditis, tubulopathy, nephrotic syndrome, vascular accident or retinitis pigmentosa. Patients with CDGS type Ib present with liver disease, enteropathy and hypoglycemia without neurologic involvement. These patients are successfully treated with oral mannose administration emphasizing the importance of making the diagnosis. Patients with CDGS type Ic present with mild psychomotor retardation and seizures. Patients with CDGS type II have psychomotor retardation association with severe gastrointestinal disorder, dysmorphic features and abnormal electroretinogram. Other types (III, IV) are less clearly defined and the clinical presentation includes convulsive encephalopathy. Biological abnormalities such as mild hepatic cytolysis, hematologic and hormonal abnormalities are consistently observed in CDGS type I, as well as renal hyperechogeneity, leading one to look for this syndrome when they are associated. Until now, only four enzymatic deficiencies have been identified (types Ia, Ib, Ic, II).
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PMID:[Carbohydrate-deficient blood glycoprotein syndrome]. 1070 Oct 64

The clinical syndrome of encephalopathy is most often encountered in the context of decompensated liver disease and the diagnosis is usually clear cut. Non-hepatic causes of encephalopathy are rarer and tend to present to a wide range of medical specialties with variable and episodic symptoms. Delay can result in the development of potentially life threatening complications, such as seizures and coma. Early recognition is vital. A history of similar episodes or clinical risk factors and early assessment of blood ammonia levels help establish the diagnosis. In addition to adequate supportive care, investigation of the underlying cause of the hyperammonaemia is essential and its reversal, where possible, will often result in complete recovery. Detection of an unborn error of metabolism should lead to the initiation of appropriate maintenance therapy and genetic counselling.
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PMID:Non-hepatic hyperammonaemia: an important, potentially reversible cause of encephalopathy. 1215 92

In patients with renal or hepatic failure, the pharmacokinetics of opioids may be affected in several ways, leading to the necessity to correct the dose. The liver is the major site for biotransformation of most opioids. The major metabolic pathway is oxidation. Exceptions to this are morphine and buprenorphine, which undergo primarily glucuronidation, and remifentanil which is cleared by esther hydrolysis. The hydrophilic metabolites are predominantly excreted by the kidneys and may accumulate in patients with renal insufficiency. Some metabolites such as morphine-6-glucuronide (M6G) or normeperidine are active opioid agonists. With high concentrations they may cause narcotic effects or respiratory depression. In addition, special risks are known for normepridine that has been shown to exert neurotoxic effects with the risk of seizures. Few cases of respiratory depression following the administration of codeine, dihydrocodeine and tramdol have been reported. The elimination half-life of these drugs was prolonged. Lastly, the disposition of methadone, buprenorphine, fentanyl, sufentanyl and remifentanil appears to be unaffected in renal failure. In patients with hepatic cirrhosis it has been shown that oxidation of opioids is reduced, resulting in a decreased drug clearance (meperidine, propoxyphene, pentazocine, tramadol and alfentanil) and increased oral bioavailability due to reduced first-pass metabolism (meperidine, propoxyphene, pentazocine, dihydrocodeine). Although glucuronidation is thought to be less affected in liver cirrhosis, the clearance of morphine was found to be decreased and its oral bioavailability increased. The consequence of reduced drug metabolism is the risk of accumulation in the body, especially with repeated administrations. As for patients with renal failure, special risks are known for meperidine with potential accumulation of normeperidine, which can cause seizures, and for propoxyphene for which several cases of hepatotoxicity have been reported. On the other hand, the analgesic activity of codeine and tilidine depends on transformation into the active metabolites, morphine and nortilidine. In the case of reduced metabolism in chronic liver disease, the analgesic action of these drugs may be compromised. Lastly, the disposition of a few opioids, such as fentanyl, sufentanil, and remifentanil, appears to be unaffected in liver disease.
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PMID:[Therapy with opioids in liver or renal failure]. 1279 31

Selecting an appropriate anticonvulsant for treatment of recipients of orthostatic liver transplants who have new-onset epileptic seizures can be challenging because first-line agents may contribute to worsening encephalopathy, alter the plasma concentration of immunosuppressive agents, and result in hepatotoxicity. We describe the case of a 55-year-old man who underwent orthotopic liver transplantation because of end-stage liver disease due to alcoholic cirrhosis and hepatitis C. He required two repeat transplantation procedures. After the last procedure, epileptic seizures developed, which were initially managed with phenytoin. However, the patient remained stuporous and mental status fluctuated. Breakthrough seizures later developed in the setting of rejection. Levetiracetam (500 mg orally, twice a day) was chosen for its favorable pharmacokinetic properties as an alternative to phenytoin. By the third day of levetiracetam therapy, the patient became more responsive. At most recent follow-up, 3 months after the start of levetiracetam therapy, the patient was still treated with levetiracetam monotherapy, and seizure control was judged to be excellent.
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PMID:Levetiracetam monotherapy for liver transplant patients with seizures. 1282 99

Therapeutic drug monitoring (TDM) is frequently utilized in the treatment of psychiatric conditions, but its clinical application concerning the use of clozapine is unclear. We present three case reports of patients taking clozapine, review the relevant literature, and propose guidelines to aid the clinical use of TDM of clozapine. Due to its complex metabolism, there are significant inter- and intra-individual variations in clozapine serum levels, for a given dose. However, the range of serum levels that corresponds with toxicity remains unclear. Although central nervous system side-effects may correlate with serum level, many adverse effects of clozapine appear to be unrelated, including haematological and cardiac events. There are numerous clinically significant interactions between clozapine and other substances, including prescribed medications, nicotine and caffeine. TDM of clozapine may be of clinical value in certain situations, such as poor clinical response; signs of toxicity; onset of seizures; changes in concurrent medication, caffeine or nicotine; liver disease; and suspected non-compliance. The current literature does not support the routine testing of serum clozapine levels in everyday clinical practice.
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PMID:Serum clozapine levels: a review of their clinical utility. 1287 May 73


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