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Anticonvulsant Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Skeletal and central nervous system and other congenital anomalies have been observed in the offspring of pregnant animals that received ethosuximide (el-Sayed et al., 1983; Sullivan and McElhatton, 1977) or methsuximide (Kao et al., 1979). Ethosuximide use in late pregnancy has been reported to be associated with neonatal hemorrhage (Bleyer and Skinner, 1976).
Critical care, neurology and analgesia
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Although ethosuximide may be effective for typical absences, it does not suppress tonic-clonic seizures, which may develop in 10 to 20% of children with childhood or juvenile-onset typical absence epilepsy. Ethosuximide may occasionally be helpful in treating myoclonic seizures. Carbamazepine exacerbates myoclonic and typical absence seizures and should therefore be avoided in juvenile myoclonic epilepsy and childhood-onset absence epilepsy.
Neurology and neurosurgery
Published in Jagdish M. Gupta, John Beveridge, MCQs in Paediatrics, 2020
Jagdish M. Gupta, John Beveridge
12.10. Childhood absence (petit mal) epilepsyhas a characteristic aura preceding an attack.commonly responds to treatment with ethosuximide.has characteristic 3/s spike and wave discharge patterns on EEG.characteristically commences between 4 and 10 years.is caused by the pertussis component in triple antigen (DPT).
An update of cyclooxygenase (COX)-inhibitors in epilepsy disorders
Published in Expert Opinion on Investigational Drugs, 2019
It is not yet clear whether these NSAIDs (nonsteroidal anti-inflammatory drugs) produce antiepileptic activity by inhibiting the COX-enzyme or if there is another mechanism. Rimoli and colleagues have shown that both DM1 (7-methyl-2-phenylimidazo[1,2-b]pyridazine-3-carboxylic acid) and DM2 (6-methoxy-2-phenylimidazo[1,2-b]pyridazine-3-carboxylic acid) are structurally similar to indomethacin (a nonselective COX-inhibitor) and possess antiepileptic activity in animal models of absence seizures [67]. However, these two compounds do not have any COX-inhibiting property. The authors of this study concluded that structurally similar compounds that do not have COX-inhibiting properties might be antiepileptic in nature. The antiepileptic activity of DM1 and DM2 may possibly be linked to their tendency to inhibit the T-type voltage-dependent calcium channels [67]. Ethosuximide remains a standard drug to treat absence seizures and works by binding to the T-type voltage-sensitive calcium channels.
T-type calcium channel blockers: a patent review (2012–2018)
Published in Expert Opinion on Therapeutic Patents, 2018
Several studies by Medium-sized Pharma, academic organizations, and Big Pharma are currently underway to develop subtype-selective T-type calcium channel blockers. It was recently reported that an antiparkinsonian effect was lacking in MPTP-treated parkinsonian monkeys following injections with the pan-T-type calcium blocker ML218 (CID45115620), a clinical candidate to treat Parkinson’s disease [77]. Ethosuximide failed to treat neuropathic pain in humans [78]. Both compounds failed due to adverse and sedative effects observed in dosing studies. ABT-636 and MK-8998 also failed in human clinical trials for pain/schizophrenia treatment [79,80]. Therefore, subtype-selective T-type calcium channel blockers have attracted attention due to their potential to offer a new generation of safe and effective drugs for pain-related diseases, including neuropathic, diabetic, and cancer-related pain. Mismatched efficacy in vivo, based on in vitro predictions designed to overcome disadvantages associated with the evaluation of neuropathic pain and epilepsy, is a complicating factor in in vivo models. Nevertheless, most compounds tested in an in vivo animal model have demonstrated effectiveness in managing pain (inflammatory, acute, and neuropathic) and in some cases demonstrated fast-acting neuropathic pain alleviation compared with a reference compound, such as gabapentin. Therefore, combination therapy or a systemic dose control treatment with the primarily used pain-treatment drug may play an important role in alleviating neuropathic, diabetic, and late-stage cancer pain.
Emerging drugs for the treatment of Dravet syndrome
Published in Expert Opinion on Emerging Drugs, 2018
Francesco Brigo, Pasquale Striano, Ganna Balagura, Vincenzo Belcastro
Several AEDs that are not specifically license for DS may be considered as adjunctive therapy options. All are broad-spectrum in their modes of action and may therefore be useful in treating multiple seizure types. Levetiracetam and topiramate particularly may be a useful adjunct as it has few interactions with other medications (expert opinion), although topiramate has a high association with cognitive and behavioral adverse events and may, rarely, cause Stevens-Johnson syndrome. Ethosuximide can be useful for the treatment of absence seizures, but should always be combined with an AED that is effective in treating convulsive seizures. CBD has class I evidence of efficacy and an adequate safety profile when used as adjunctive therapy and it is generally well tolerated although it is a potent inhibitor of enzymes in the cytochrome P450 pathway, and a definitive interaction has been reported with at least clobazam.