Anticonvulsant Therapy in Children: An Update

1996 ◽  
Vol 9 (1) ◽  
pp. 27-41
Author(s):  
Judith L. Scala ◽  
Cathy Y. Poon
Keyword(s):  
Adverse Effects ◽  
The United States ◽  
New Drugs ◽  
Adjunctive Treatment ◽  
Partial Seizures ◽  
Intractable Seizures ◽  
Generalized Seizures ◽  
Life Threatening ◽  
Pediatric Use ◽  
New Generation

Over the years, extensive research has led to the development of a new generation of anticonvulsant medications for the treatment of patients with intractable seizure disorders. Currently three new drugs have been approved in the United States since 1993, and many others have entered into the later stages of development. The purpose of this article is to discuss the pharmacology, pharmacokinetics, drug interactions, clinical use, adverse effects, and dosage and administration of felbamate, gabapentin, lamotrigine, and vigabatrin. Felbamate is indicated in children as adjunctive therapy in the treatment of partial and generalized seizures secondary to Lennox-Gastaut syndrome. Because of life-threatening adverse effects, including aplastic anemia and hepatotoxicity, felbamate is reserved for use only when the benefits of treatment outweigh the risks of toxicity. Presently, gabapentin is indicated as adjunctive treatment of partial seizures with or without generalization in patients older than 12 years of age. To date gabapentin has not been studied in patients younger than age 12 years. Even though lamotrigine is not approved by the Food and Drug Administration (FDA) for pediatric use, preliminary clinical trials show promising results in the treatment of partial and absence seizures as well as Lennox-Gastaut syndrome. Many studies have evaluated the use of vigabatrin for the treatment of intractable seizures. Seizure types most effectively treated include partial seizures, Lennox-Gastaut syndrome, and possibly infantile spasms. Lamotrigine and vigabatrin should be used with caution in patients with myoclonic seizures because an increase in seizure frequency may occur. Copyright © 1996 by W.B. Saunders Company

Severe pulmonary complications in Japanese patients after bortezomib treatment for refractory multiple myeloma

Blood ◽  
2006 ◽  
Vol 107 (9) ◽  
pp. 3492-3494 ◽  
Author(s):  
Shigesaburo Miyakoshi ◽  
Masahiro Kami ◽  
Koichiro Yuji ◽  
Tomoko Matsumura ◽  
Masaaki Takatoku ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Effects ◽  
Gastrointestinal Symptoms ◽  
Japanese Patients ◽  
The United States ◽  
Underlying Disease ◽  
Pulmonary Complications ◽  
Bortezomib Treatment ◽  
Toranomon Hospital ◽  
Life Threatening

Bortezomib is a novel proteasome inhibitor with significant antimyeloma activity. Its frequent adverse effects are manageable, including gastrointestinal symptoms, peripheral neuropathy, and thrombocytopenia. Severe lung toxicity has not previously been reported. Between June 2004 and September 2005, 13 Japanese patients with multiple myeloma were treated with bortezomib in Toranomon Hospital, Juntendo University School of Medicine, and Jichi Medical School. Four of them developed severe pulmonary complications, and 2 died of respiratory failure without progression of underlying disease. To our knowledge, this is the first report on life-threatening pulmonary adverse effects after bortezomib therapy. Previous clinical studies on bortezomib, mostly in the United States and Europe, have shown low incidences of pulmonary adverse effects. Our study suggests that bortezomib can cause serious lung injury, and that its incidence might vary among different ethnicities. Clinicians need to be alert to the possibility.

Pimozide Treatment of Tic and Tourette Disorders

PEDIATRICS ◽  
1987 ◽  
Vol 79 (6) ◽  
pp. 1032-1039
Author(s):  
Arthur K. Shapiro ◽  
Elaine Shapiro ◽  
George Fulop
Keyword(s):  
Adverse Effects ◽  
The United States ◽  
Tic Disorders ◽  
New Drugs ◽  
Neuroleptic Drug ◽  
Number Of Patients ◽  
Erroneous Belief ◽  
Detection And Diagnosis ◽  
Tourette Disorder ◽  
Early Detection And Diagnosis

Tourette disorder is a chronic multiple tic condition that begins in childhood and may require lifelong treatment. Neuroleptics are the most effective and frequently used drugs for the treatment of both Tourette and tic disorders. Haloperidol was the first neuroleptic drug approved by the Food and Drug Administration (FDA) for the treatment of adult patients with Tourette disorder in 1969 and for children in 1978. Its effectiveness in the treatment of tics is well documented.1,2 However, adverse effects limit its usefulness and new drugs that have fewer adverse effects and greater efficacy are needed.2-5 The need for new medications is critical because of the epidemic increase in the number of patients with the diagnosis. We now know that Tourette disorder was underdiagnosed because of the erroneous belief that the etiology was psychologic and that the diagnosis required the presence of coprolalia, echolalia, and intellectual and psychologic deterioration. Following the development of accurate diagnostic criteria, early detection and diagnosis was facilitated. This in turn led to a dramatic increase in the number of physicians diagnosing and treating tic disorders and the establishment of Tourette disorder clinics throughout the country. The lifetime prevalence in the United States is now estimated as 0.5% for Tourette disorder and 1.6% for both Tourette and chronic motor tic disorders.6,7 However, a new neuroleptic drug, pimozide, was recently approved by the FDA for use in patients with Tourette disorder in 1984. Our studies on the effectiveness of pimozide, begun in 1977, were largely responsible for appoval of pimozide.

P5677Ictal asystole and bradycardia patients with epilepsy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R A Teryan ◽  
S E Serdyuk ◽  
K V Davtyan ◽  
O M Drapkina
Keyword(s):  
Partial Seizure ◽  
Partial Seizures ◽  
Loop Recorder ◽  
Cardiac Pacemakers ◽  
Generalized Seizures ◽  
Life Threatening ◽  
Epilepsy Localization ◽  
Temporal Localization ◽  
Patients With Epilepsy ◽  
Special Patient

Abstract Background Events of ictal bradycardia or asystole may be of importance in epilepsy patients showing with ictal falls and are a funder to SUDEP. With using implantable loop recorders, we can detect ictal bradycardia or asystole. And implantation of cardiac pacemakers may prevent life-threatening syncope, cardiac arrest, and disturbances. Purpose The purpose of this study is to look at how many ictal bradycardia or asystole and match with localization, types of seizure and antiepileptic drugs in a patient with hard to treat epilepsy. Methods Patients with hard to treat epilepsy were implanted loop recorders. Patients or their relations were activated loop recorder (with a special patient assistant) during or after seizure depending on the type of seizure. Results 204 patients included in the study. The mean duration of loop recording 24 months. 1168 ECG seizure were reordered of 204 patients, 494 (42%) secondary generalized seizures and 674 (58%) partial seizures. Nine patients (4%) were recorded ictal bradycardia and ictal asystole. Only four patients with ictal asystole and bradycardia take AED (antiepileptic drug) inhibit sodium channels. During seizure were recorded only 14 (1, 1%) seizure with ictal asystole and bradycardia of nine patients, 6 (42%) – with ictal asystole (5 – SA-block, 1 – AV-block), 8 (57%) – ictal bradycardia. Ten (71%) events of 14 was secondary generalized seizures, 4 (28%) - partial seizures. Five ictal asystoles recorded during secondarily generalized seizures, and only 1 partial seizure. Five ictal bradycardias reordered during secondarily generalized seizures, 3 - partial seizure. Frontal-temporal localization only 4 patients, 1 – occipital-frontal, 1 – frontal, 3 – without consistent epilepsy localization. Three patients with bilateral lateralization, 2 – left lateralization, 1 – right lateralization, 3 – without consistent epilepsy lateralization. Conclusions Ictal asystole can be problematic to diagnose because of both its under-recognition and its appearance only during seizures. In this study, we showed the most life-threatening events occurred in patients with the secondarily generalized seizures. Bradyarrhythmias can one of possible sudden unexplained death in epilepsy patients (SUDEP). No clear association was seen between ictal bradycardia/asystole and lateralization or localization of seizure onset.

Vigabatrin in Refractory Complex Partial Seizures: The Evidence of its Therapeutic Value

2010 ◽  
Vol 2 ◽  
pp. CMT.S3788
Author(s):  
Michele A. Faulkner ◽  
Justin A. Tolman
Keyword(s):  
Vision Loss ◽  
Peripheral Vision ◽  
The United States ◽  
Adjunctive Treatment ◽  
Partial Seizures ◽  
Complex Partial Seizures ◽  
Psychiatric Disturbances ◽  
Therapeutic Value ◽  
Number Of Patients ◽  
Unites States

Vigabatrin (Sabril®) has recently been granted approval in the Unites States for the adjunctive treatment of complex-partial seizures in adults. The drug was first evaluated as a potential therapy for this population decades ago, and it has been available in other parts of the world for some time. Well controlled studies demonstrate that at doses up to 3 g/day, the drug is efficacious as add-on therapy for treatment resistant seizures. However, vigabatrin has been associated with significant side-effects limiting its use, and relegating it to a late therapeutic alternative. Specifically, vigabatrin has been implicated in the development of irreversible peripheral vision loss in a significant number of patients. For this reason, the approval of the drug in the United States was contingent upon the introduction of a rigorous monitoring protocol that must accompany its use. Additionally, the drug has been associated with a relatively high incidence of psychiatric disturbances, although there is disagreement about a direct correlation of these symptoms to the drug. Still, the drug remains a viable alternative for patients who have failed therapy with traditional anti-seizure medications.

New Antiepileptic Drugs for Children: Felbamate, Gabapentin, Lamotrigine, and Vigabatrin

1994 ◽  
Vol 9 (1_suppl) ◽  
pp. S33-S45 ◽  
Author(s):  
Orrin Devinsky ◽  
Blanca Vazquez ◽  
Daniel Luciano
Keyword(s):  
United States ◽  
Antiepileptic Drugs ◽  
The United States ◽  
Partial Epilepsy ◽  
New Drugs ◽  
Pediatric Epilepsy ◽  
Partial Seizures ◽  
Safety And Efficacy ◽  
New Antiepileptic Drugs ◽  
Important Addition

After a 15-year hiatus, several new antiepileptic drugs have been approved or are under Food and Drug Administration investigation for use in the United States. This article reviews four of these new drugs—felbamate, gabapentin, lamotrigine, and vigabatrin. Although these drugs have been primarily developed for use in adults with partial seizures, they will also likely be used in children with partial epilepsy. Pediatric experience with several of these drugs has demonstrated safety and efficacy in other seizure types and epilepsy syndromes. These drugs will be an important addition to the therapeutic armamentarium for pediatric epilepsy. Additional studies are needed to fully explore the safety and efficacy of these drugs in a variety of pediatric epilepsies and to compare them to existing antiepileptic drugs. (J Child Neurol 1994;9(Suppl):S33-S45).

Lamotrigine in Absence and Primary Generalized Epilepsies

1997 ◽  
Vol 12 (1_suppl) ◽  
pp. S29-S37 ◽  
Author(s):  
Mohamad A. Mikati ◽  
Gregory L. Holmes
Keyword(s):  
Young Patients ◽  
The United States ◽  
Seizure Type ◽  
Newly Diagnosed ◽  
Partial Seizures ◽  
Open Label ◽  
Absence Seizures ◽  
Generalized Seizures ◽  
Clonic Seizures ◽  
Eeg Recordings

Although lamotrigine has been approved in the United States as adjunctive therapy for partial seizures in patients older than 12 years, there is increasing evidence that it is just as effective, if not more effective, in the treatment of generalized seizures. A large number of open-label studies and some single-blind data, all using lamotrigine as add-on therapy in patients with previously refractory generalized seizures, are available. Controlled studies, some on newly diagnosed, previously untreated patients with generalized seizures are ongoing. Investigations have demonstrated that patients with the following generalized seizure types improve with lamotrigine add-on therapy: Typical and atypical absence, atonic, generalized tonic-clonic, myoclonic, and clonic seizures. Response rates, defined as the percentage of patients with better than 50% reduction in seizure frequency, have been, depending on seizure type, in the range of 30% to 56%, with 0 to 33% of the patients becoming seizure free. The best responses have been noted in typical and atypical absences, and atonic seizures. Children and adults appear to have comparable responses. In addition, add-on studies in patients with specific, previously refractory, epilepsy syndromes have demonstrated that the best improvement in seizure control occurs in patients with petit mal epilepsy, "other symptomatic" generalized epilepsies, and in Lennox-Gastaut syndrome, followed by patients with other myoclonic epilepsies, myoclonic absence and West syndrome. Many previously refractory patients are able to achieve lamotrigine monotherapy. However, patients with nonprogressive myoclonic epilepsy have little, if any, response. Early data from ambulatory encephalographic (EEG) recordings in patients with previously refractory absence seizures, and from controlled studies on patients with newly diagnosed typical absence seizures, appear to confirm the efficacy of lamotrigine in those patients. Controlled studies are ongoing in patients with absence seizures, in patients with generalized tonic-clonic seizures, and in patients with Lennox-Gastaut syndrome. Dosing in generalized seizures is similar to that for partial seizures. Because of the shorter half-life of lamotrigine in children, as compared to adults, higher (mg/kg) doses are often needed in young patients. We conclude that lamotrigine is a promising drug for absence and primary generalized seizures in both children and adults. (J Child Neurol 1997;12(Suppl 1):S29-S37).

New Drugs of 2012: A Concise Overview of the NMEs and Trends for Innovative Brand Market in the United States

2013 ◽  
Vol 6 (2) ◽  
pp. 2009-2013
Author(s):  
D Samba Reddy
Keyword(s):  
Drug Approval ◽  
The United States ◽  
New Drugs ◽  
New Combination ◽  
Drug Status ◽  
Combination Drug ◽  
Human Cord Blood ◽  
Life Saving ◽  
Genomics And Proteomics ◽  
The Face

Thirty-nine (39) new drugs have been approved by the U.S. FDA in 2012, a record highest number of approvals since 1996. The record is a sign that pharma companies are poised to tap recent advances from genomics and proteomics. This list includes novel new drugs, known as new molecular entities (NMEs), biologics and new products. Many life-saving drugs are approved for marketing. The list includes a total of 10 drugs for cancer treatment, and nearly a quarter of those approved in 2012 had orphan drug status.  Among the breakthrough drugs approved in 2012 were ivacaftor (cystic fibrosis), vasmodegib (skin cancer), HPC-C (human cord blood product), ruxolitinib (myelofibrosis) and a new combination drug to treat HIV. In addition,  several unique products were approved for the treatment of macular degeneration, chronic weight management, overactive bladder, actinic keratosis, erectile dysfunction, glaucoma, respiratory distress syndrome, and COPD. The approval of 39 drugs in 2012 underscores a robust success rate and confirms that innovation is once again beginning to pay off. In the existing climate of reduced revenues in the face of generic competitions, the future and survival of big companies rests heavily on their unique niche products. It is apparent that big Pharma and a growing number of emerging Biotechs alike have focused their attention on developing new NMEs for rare diseases. In 2012, the length of the FDA’s review is shorter than agencies in other countries. Innovative models adopted for R&D strategies, communications, and new regulatory changes appear to shorten development timelines. Despite record drug approvals, there is bleak scope for blockbusters because most of these drugs have a limited market. The pipeline for blockbusters appears very low. However, there is unmet medical need for new drugs in autism, Alzheimer’s disease and epilepsy. Overall, the new drug approval list unveils unique and reemerging trends indicating that the pharma companies are poised for big growth from new brands approved for marketing for narrow-spectrum indications.    

The Chemistry of Drugs to Treat Candida albicans

2019 ◽  
Vol 19 (28) ◽  
pp. 2554-2566 ◽  
Author(s):  
Aurelio Ortiz ◽  
Estibaliz Sansinenea
Keyword(s):  
Candida Species ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Drug Classes ◽  
Life Threatening ◽  
Antifungal Substances ◽  
High Level ◽  
Systemic Infections ◽  
New Compounds ◽  
Level Resistance

Background:: Candida species are in various parts of the human body as commensals. However, they can cause local mucosal infections and, sometimes, systemic infections in which Candida species can spread to all major organs and colonize them. Objective:: For the effective treatment of the mucosal infections and systemic life-threatening fungal diseases, a considerably large number of antifungal drugs have been developed and used for clinical purposes that comprise agents from four main drug classes: the polyenes, azoles, echinocandins, and antimetabolites. Method: : The synthesis of some of these drugs is available, allowing synthetic modification of the molecules to improve the biological activity against Candida species. The synthetic methodology for each compound is reviewed. Results: : The use of these compounds has caused a high-level resistance against these drugs, and therefore, new antifungal substances have been described in the last years. The organic synthesis of the known and new compounds is reported. Conclusion: : This article summarizes the chemistry of the existing agents, both the old drugs and new drugs, in the treatment of infections due to C. albicans, including the synthesis of the existing drugs.

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