Absence Seizures and Carbamazepine in Adults

Summary: Carbamazepine (CBZ) therapy was associated with development of absence seizures in 4 adults with generalized epilepsy. Two patients had new appearance of absence seizures and 2 patients had recrudesence of remote absence seizures. The seizures abated after discontinuation of CBZ therapy or addition of ethosuximide (ESM) in 1 patient intolerant of valproate (VPA).     

Effects of carbamazepine on acute responses to smoked cocaine-base in human cocaine users

A double-blind, placebo-controlled cross-over study was conducted to determine the effects of carbamazepine on the acute physiological and subjective responses to a single dose of smoked cocaine-base. Male cocaine users (N=6) were given 400 mg carbamazepine or placebo, each for a period of 5 days. At the end of the 5-day period, a 40 mg dose of smoked cocaine was administered. The results showed a significantly higher heart rate, diastolic blood pressure elevation, and blood pressure-heart rate product under the carbamazepine compared to the placebo condition. There were no effects of carbamazepine on the subjective responses from cocaine. The increase in cardiovascular functions indicates a need to be cautious in the use of carbamazepine in the treatment of cocaine abusers.Supported by National Institute on Drug Abuse Research Grant No. DA05844     

Carbamazepine-induced skin rash in children with epilepsy

The clinical and epidemiological findings in children with epilepsy who experienced skin rashes induced by carbamazepine (CBZ) were prospectively evaluated. Thirty-three (9.9%) of 335 patients who received CBZ therapy experienced a skin rash. Seven had diffuse erythema, 13 miliary exanthema, 11 maculopapular or speckled reddish rash, 3 petechiae, and 2 mucocutaneous syndrome. A skin rash was more frequent in older children (over 6 years old). The skin rashes appeared soon after initiation of the therapy, i.e., from the 8th to 60th day (mean: 14.3±9.6 days) after the start of CBZ therapy and disappeared within a few days after discontinuation of the therapy. Haematological abnormalities (30.3%), such as leucocytopenia and thrombocytopenia, and hepatic dysfunction (27.3%) sometimes appeared concomitantly with the skin rash. CBZ is an effective and safe antiepileptic drug, but careful management is necessary on initiation of the therapy.     

Electrochemical properties of Langmuir—Blodgett films of polyesters derived from oligothiophenes

The electrochemical properties of polyesters derived from oligothiophenes have been studied in solution, and as Langmuir—Blodgett (LB) and cast films. Polyesters with four or five thiophene units exhibited a well-defined voltammetric response and good LB transfer characteristics. Mono and multilayer LB films were electroactive with clear symmetrical peaks, better developed than for the cast films. These films can be p- or n-doped electrochemically.     

苯妥因钠、丙戊酸钠、卡马西平对癫痫患者智力的影响

抗癫痫药物造成认知功能的损害及损害程度迄今仍无明确结论。为此，我们对46例全面性强直一阵挛发作的癫痫患儿进行了服药前后的智力测验，并以16例健康同龄人对照，以检测苯妥因钠、丙戊酸钠、卡马西平对智力的影响。结果表明：服药3－4个月后，在血药浓度水平于治疗范围内的情况下，苯妥因钠组病人的操作智商，知觉组织智高较对照组低（P＜0．05），而丙戊酸钠组及卡马西平组相互比较并与对照组比较则元显著差异。提示苯妥因销影响患儿的记忆、注意、抽象思维能力、空间知觉能力及学习能力，而丙戊酸钠及卡马西平对智力则无明显影响。     

逆转录巢式聚合酶链反应检测重型肝炎患者血清HGVRNA及分析

采用逆转录巢式聚合酶链反应技术检测重型肝炎患者血清ＨＧＶＲＮＡ，并与临床病死率间关系进行了初步探讨。结果发现２２例重肝患者血清标本中检出６例ＨＧＶＲＮＡ阳性，阳性率２７．３％，其中亚急性重型肝炎１１例，ＨＧＶＲＮＡ阳性４例，阳性率３６．４％，慢性重型肝炎１０例，ＨＧＶＲＮＡ阳性２例，阳性率２０．０％，急性重型肝炎１例未检出。ＨＧＶＲＮＡ阳性６例中，死亡１例，死亡率１６．７％，ＨＧＶＲＮＡ阴性１６例中，死亡６例，死亡率３７．５％。表明川北地区亦存在ＨＧＶ感染，ＨＧＶ感染病例病死率较低，预后好     

Interictal Cardiovascular Autonomic Responses in Patients with Epilepsy

Summary: Purpose: To evaluate the interictal autonomic nervous system function in 84 patients with epilepsy: 37 with newly diagnosed, previously untreated epilepsy, and 47 patients receiving long-term carbamazepine (CBZ), phenytoin (PHT), or valproate (VPA) monotherapy, or CBZ plus PHT, or CBZ plus VPA for their seizure disorder. Methods: We assessed autonomic control of the cardiovascular regulatory system, by standardized cardiovascular reflex tests measuring changes in heart rate (HR) and blood pressure (BP) at rest and after certain stimuli. Results: The HR and BP responses were similar to those of control subjects in patients with newly diagnosed epilepsy. However, HR variation during normal breathing and maximum systolic BP increase in isometric work were diminished in patients, who had been treated with antiepileptic drugs (AEDs) for epilepsy for a long time. Diminished HR responses to the Valsalva maneuver were noted in patients receiving CBZ as monotherapy and during deep breathing in patients receiving CBZ combined with PHT or VPA. Furthermore, patients receiving CBZ had diminished BP responses in isometric work. When analyzed in relation to epilepsy type, suppressed HR responses in normal breathing were associated with primary generalized epilepsy (PGE), whereas diminished BP responses in isometric work were associated with partial epilepsy. Two patients with recently diagnosed partial epilepsy and 1 patient receiving long-term CBZ monotherapy for partial epilepsy had two abnormal cardiovascular response test results. Conclusions: Our results show that cardiovascular responses mediated by both the parasympathetic and sympathetic nervous system are diminished in patients with epilepsy. However, the changes appear to be clinically significant in only a few of them and appear to be associated with CBZ medication. Further studies are needed to detect the underlying complex interactions and clinical significance of autonomic nervous system dysfunction in patients with epilepsy.     

Carbamazepine Toxicity with Lamotrigine: Pharmacokinetic or Pharmacodynamic Interaction?

Summary: Purpose: To determine whether the toxicity that occurs in some patients when lamotrigine (LTG) is added to carbamazepine (CBZ) is the result of either a pharmacokinetic or a pharmacokinetic or a pharmcodynamic interaction.
Methods: Escalating LTG doses were added to ongoing CBZ treatmcnt in 47 patients. All patients had blood samples collected for drug concentration measurement, including the epoxide metabolite of CBZ, before starting LTG treatment and after stabilising at each dose escalation. Patients also were examined for signs of toxicity.
Results: After LTG was introduced, nine patients demonstrated clinical signs of CNS toxicity, mainly diplopia and diziness. There was no significant (p = 0.05) change in the serum concentrations of either CBZ or its epoxide metabolite when LTG was added either to the group as a whole or to the nine patients who experienced adverse CNS effects. LTG serum concentrations also were below the level at which the common signs of LTG toxicity, such as nausea, vomiting, or unsteadiness, are more likely to occur. In seven of the nine patients who exhibited CNS toxicity. CBZ serum concentrations were >8 mg/L on LTG introduction.
Conclusions: Toxicity is more likely to occur when LTG is added to CBZ if the initial CBZ level is high. typically >8 mg/L. This appears to be the result of a pharmacodynamic interaction. A reduction of CBZ dose usually resolves the toxicity, allowing the LTG dose to be escalated to maximal effect. It is not usually necessary to stop either drug.     

Carbamazepine suppresses synchronized afterdischarging in disinhibited immature rat hippocampus in vitro

Bath application of therapeutic concentrations of the anticonvulsant carbamazepine suppressed penicillin-induced synchronized afterdischarging in immature rat CA₃ hippocampal pyramidal cells. Afterdischarging was completely abolished in all preparations at a concentration of 30 μM (IC₅₀ = 8.5 ± 1.4 μM; mean ± S.E.M.). The duration of the preceding epilptiform burst was not altered at this concentration and was diminished by only 24.4 ± 1.2% at a supratherapeutic concentration of 100 μM. These results suggest that a carbamazepine-sensitive neurophysiological mechanism distinct from those responsible for epileptiform burst generation plays a key role in the generation of afterdischarges in developing hippocampus.     

Central Hypotensive Effects of Nicardipine in Conscious Freely Moving Spontaneously Hypertensive Rat

The central cardiovascular effects of the calcium channel blocker nicardipine was studied in conscious freely moving normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Nicardipine was administered in a 1.5 μ1 volume into the lateral ventricle of the brain (i.c.v.) or intravenously (i.v.). The injection of vehicle alone did not significantly change mean arterial pressure (MAP) or heart rate (HR). Nicardipine (10,30,100 and 300 μg/kg), intravenously administered, dose-dependently decreased MAP and increased HR in WKY and SHR. However, when administered i.c.v., nicardipine (10 μg/kg) increased MAP and HR in WKY and decreased MAP without any significant change in HR in SHR. These results are consistent with previous work reporting an exaggerated hypotensive response to i.c.v. administration of dihydropyridine calcium channel blockers in anesthetized SHR as compared to WKY. They suggest that a 1,4–dihydropyridine-sensitive pressor system is present in the SHR but not in the WKY.