Epileptic effect

Olpe H, Kolb CN, Hausdorf A, et al 4-Aminopyridine and barium chloride attenuate the anti-epileptic effect of carbamazepine in hippocampal slices. Experientia 47 254-257, 1991... 

Khalilov, I, Hirsch, J, Cossart, R, Ben-Aii, Y (2002) Paradoxical anti-epileptic effects of a GluR5 agonist of kainate receptors. J Neurophysiol, 88 523-527. 

During evaluation of the effect of vitamin D given together with anticonvulsant drugs in a controlled therapeutic trial in epileptic patients such side effects as hyper-calcaemia and raised serum alkaline phosphatase levels were observed, but the number of seizures could be reduced (53 ). TTie results of this study suggest that epileptics should be treated prophylactically with vitamin D. The anti-epileptic effect of vitamin D appears to be imrelated to changes in serum calcium or magnesium. 

Similarly, convulsive seizures and a sustained epileptic state persisted after stomach contents were pumped and activated charcoal and anticonvulsive medication were administered in a 43-year-old man who ingested approximately 260 mg/kg endosulfan (Boereboom et al. 1998). At 4 days after exposure, the man was pronounced brain dead, and autopsy revealed cerebral hernia from massive cerebral edema. Eight additional accidental and/or intentional cases of acute poisoning with endosulfan resulting in adverse neurological effects have been reported in more recent studies, six by Blanco-Coronado et al. (1992), one by Lo et al. (1995), and one by Pradhan et al. (1997) two out of the eight resulted in death. Tonic-clonic convulsions were seen in the Blanco-Coronado et al. (1992) cases, whereas Lo et al. (1995) reported the development of muscle fasciculations and episodes of convulsions in their case. In the case reported by Pradhan et al. (1997), the patient had consumed about 75 mL of hquid endosulfan (35% w/v). In this case, in addition to tonic-clonic seizures and myoclonic jerks, the patient developed... 

All such animal procedures suffer from the obvious and basic problem that laboratory animals do not behave like humans and that humans cannot reliably interpret their reactions and behaviour. Thus we know that Parkinson s disease is caused by a degeneration of the dopaminergic nigrostriatal tract but its lesion in animals does not produce any condition which resembles human Parkinsonism, except in primates, even though there are functional tests (e.g. rotational movements) which readily establish that loss of dopamine function and also respond to its augmentation (Chapter 15). By contrast, there are many ways, e.g. electrical stimulation and the administration of certain chemicals, to induce convulsions in animals and a number of effective antiepileptic drugs have been introduced as a result of their ability to control such activity. Indeed there are some tests, as well as animals with varied spontaneous seizures, that are even predictive of particular forms of epilepsy. But then convulsions are a very basic form of activity common to most species and epileptic seizures that are characterised by behavioural rather than motor symptoms are more difficult to reproduce in animals. 

The widespread and diverging nature of ascending monoamine pathways to the cortex suggest that NA and 5-HT are more likely to have a secondary modifying rather than a primary effect on the initiation of epileptic activity. In reality this is the case and their secondary role is even a minor one. Generally a reduction in monoamine function facilitates experimentally induced seizures (see Meldrum 1989) while increasing it reduces seizure susceptibility. The variability of the procedures used and results obtained do not justify more detailed analysis here. 

There is no shortage of AEDs (Fig. 16.7) but it is not appropriate to consider them in detail in this text other than to see how their mechanisms of action comply with and illustrate those proposed above (Fig. 16.6) for the control of epileptic seizures (see Meldrum 1996 Upton 1994). The decision on which drug to use depends not only on their proven efficacy in a particular type of epilepsy (some drugs are inactive in certain forms) but also what side-effects they have—many are sedative — how they interact with other drugs and how often they need to be taken. Compliance is a problem over a long period if dosing is required more than once a day. It is probably acceptable in reality, if not scientifically, to divide the drugs into old-established AEDs and new AEDs. Only the latter have been developed chemically to modify the known synaptic function of the amino acids. 

Use of diethylpropion for a period longer than 3 months is associated with an increased risk for development of pulmonary hypertension. When used as directed, reported common central nervous system adverse effects included overstimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, headache, jitteriness, anxiety, nervousness, depression, drowsiness, malaise, mydriasis, and blurred vision. In addition, diethylpropion can decrease seizure threshold, subsequently increasing a patient s risk for an epileptic event. Other organ systems also can adversely be affected, resulting in tachycardia, elevated blood pressure, palpitations, dry mouth, abdominal discomfort, constipation,... 

Secobarbital exhibits the same pharmacologic properties as other members of the barbiturate class. Most nonmedical use is with short-acting barbiturates, such as secobarbital. Although there may be considerable tolerance to the sedative and intoxicating effects of the drug, the lethal dose is not much greater in addicted than in normal persons. Tolerance does not develop to the respiratory effect. The combination of alcohol and barbiturates may lead to fatalities because of their combined respiratory depressive effects. Similar outcomes may occur with the benzodiazepines. Severe withdrawal symptoms in epileptic patients may include grand mal seizures and delirium. 

Colasanti BK, Lindamood C 3d, Craig CR. (1982). Effects of marihuana cannabinoids on seizure activity in cobalt-epileptic rats. Pharmacol Biochem Behav. 16(4) 573-78. 

Dalby, N. O. Inhibition of gamma-aminobutyric add uptake anatomy, physiology and effects against epileptic seizures. Eur. J. Pharmacol. 2003, 479, 127-137. 

Phenytoin is an anti-epileptic drug. Patients taking anti-epileptic drugs are advised to take the medicine routinely, as directed, to stabilise and to avoid epileptic attacks as much as possible. Phenytoin has a narrow therapeutic index so it is important to identify side-effects. It may cause blood disorders. Patients are therefore advised to report immediately any symptoms of bruising or unexplained bleeding. Visual symptoms as a result of phenytoin do not commonly occur. Their occurrence may indicate overdosage. 

Largactil is a proprietary preparation of chlorpromazine, an aliphatic antipsychotic with marked sedation and moderate antimuscarinic and extrapyramidal side-effects. Serenace is a proprietary preparation of haloperidol, a butyrophenone antipsychotic with marked extrapyramidal side-effects, moderate sedation but not very likely to cause hypotension. Tegretol is a proprietary preparation of carbamazepine, an anti-epileptic drug indicated in partial and secondary generalised tonic-clonic seizures, primary generalised tonic-clonic seizures, trigeminal neuralgia and in the prophylaxis of bipolar disorder unresponsive to lithium. 

Carbamazepine is used principally for major epileptic attacks. It is not effective enough for minor attacks. There are data showing a number of side effects. A synonym of carbamazepine is tegretol. 

Whether there is any other connection between anticonvulsant activity and camosine s antiaging actions is obviously highly speculative. It may be relevant to note that epileptic seizures and a shortened life span, together with altered protein accumulation, are consequences of PIMT-deficiency in mice, while treatment with valproic acid, an anticonvulsant, partially suppresses these symptoms including effects on life span (Yamamoto et ah, 1998). Conversely, PIMT overexpression can increase life span of Drosophila (Bennet et ah, 2003). Furthermore, the chemistry of some anticonvulsants (ethosuximide) resembles quite closely the structure of the succinimide intermediate formed during both asparagine deamidation and PIMT-mediated repair of isoaspartate residues. One conjectures whether there are any relationships between these... 

Baclofen is a GABA agonist at GABA B receptors and it has a presynaptic inhibitory function by reducing calcium influx. Its indication is increased extensor tone and clonus. Intrathecal administration may control severe spasticity pain. It is used for the treatment of spastic movement, especially in instances of spinal cord injury, spastic diplegia, multiple sclerosis and amyotrophic lateral sclerosis. Its central nervous system effects include drowsiness, somnolence and seizure activity in epileptic patients. 

Anti-epileptic drugs - - effective in neuropathic pain ... 

Finally, a systematic review of ten trials including 2036 patients dealing with the prevention of seizures after brain injury concludes Prophylactic anti-epileptics are effective in reducing early seizures, but there is no evidence that treatment with prophylactic anti-epileptics reduces the occurrence of late seizures, or has any effect on death and neurological disability. Insufficient evidence is available to establish the net benefit of prophylactic treatment at any time after injury . 

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