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Antiepileptics & Status Epilepticus
- 1. ANTICONVULSANT DRUGS STATUS EPILEPTICUS STAJYER DOKTOR ALI HAMZA
- 2. Anticonvulsant drugs inhibit neural activity (↓ neural excitation, ↑ neural inhibition) and increase the seizure threshold by interacting with specific receptors and ion channels.
- 3. First-generation anticonvulsants Compared to second-generation anticonvulsants, first-generation anticonvulsants have a narrower therapeutic range, more severe side effects, and a wider range of drug interactions Valproate Carbamazepine Ethosuximide Phenytoin,Fosphenytoin Phenobarbital Benzodiazepines
- 4. Second-generation anticonvulsants Second-generation anticonvulsants have a broader therapeutic range, fewer side effects, and fewer interactions with other drugs Lamotrigine Tiagabine Levetiracetam Pregabalin Gabapentin Topiramate
- 5. Valporate Indication • First-line long-term treatment for tonic-clonic generalized seizures • Partial (focal) seizures • Absence epilepsy • Treatment of established status epilepticus • Myoclonic seizures • Migraine prophylaxis • Bipolar disorder Adverse effects • Gastrointestinal upset • Tremor • Alopecia • Pancreatitis • Weight gain • Teratogenicity • Hepatotoxicity (rare): LFT should be regularly performed in people taking valproate • Cytochrome P450 inhibition • Rash • Sedation • Ataxia • Thrombocytopenia • Agranulocytosis
- 6. Carbamazepine Indication • First-line treatment for focal seizures • First-line treatment of trigeminal neuralgia • Second-line treatment for generalized tonic-clonic seizures Adverse effects • Nausea • Rash • Hyponatremia, hyperhydration, and edema (due to SIADH) • DRESS syndrome • Blood count abnormalities (e.g., agranulocytosis, aplastic anemia) • Teratogenicity during the first trimester • Ataxia • Hepatotoxicity • Stevens-Johnson syndrome • Induces cytochrome P450
- 7. Ethosuximide Indication • First-line for absence seizure Adverse effects • Gastrointestinal symptoms • Allergic skin reactions (urticaria, Stevens-Johnson syndrome) • Pancytopenia • Fatigue • Headache • Myopia •Teratogenicity
- 8. Phenytoin, fosphenytoin Indication • Tonic-clonic seizures • Only rarely used for long-term treatment of focal seizures • Treatment of established status epilepticus Adverse effects • Hirsutism • Hyperpigmentation of skin (melasma) • Gingival hyperplasia • Nystagmus • Osteopenia • Megaloblastic anemia due to ↓ folate absorption • Peripheral neuropathy • Stevens-Johnson syndrome • Drug-induced lupus erythematosus • DRESS syndrome • Intoxication: sedation, diplopia, ataxia, arrhythmias • Induction of cytochrome P-450 enzymes • Teratogenic: fetal hydantoin syndrome • Hypothyroidism
- 9. Phenobarbital Indication • First-line treatment in neonates • Tonic-clonic generalized seizures • Focal seizures • Status epilepticus Adverse effects • Cardiorespiratory depression • Tolerance and dependence • Sedation • Induces cytochrome P-450
- 10. Benzodiazepines Indication • First-line for status epilepticus • Second-line treatment for eclampsia Adverse effects • Sedation and dependence • Tolerance • Respiratory depression
- 11. 2.Lamotrigine Indication • First-line treatment for long-term therapy of focal seizures • Second-line treatment for generalized seizures and absence seizures • Mood stabilizer for treatment of bipolar disorder Adverse effects • Rash, exfoliative dermatitis, Stevens-Johnson syndrome (slow titration is necessary to prevent skin and mucous membrane reactions) • Hemophagocytic lymphohistiocytosis
- 12. Tiagabine Indication • Focal seizures, with or without impairment of consciousness (adjunctive therapy) Adverse effects • Dizziness • Gastrointestinal upset: nausea, vomiting, diarrhea • Insomnia • Drowsiness • Weight changes
- 13. Levetiracetam Indication • First-line treatment for long-term therapy of focal seizures Generalized seizures Adverse effects • Lethargy, fatigue • Nausea • Headache • Psychiatric symptoms (e.g., personality changes)
- 14. Pregabalin Indication • Drug combination for long-term treatment of focal seizures • Neuropathic pain • Neuralgia after herpes infection • Generalized anxiety disorder Adverse effects • Somnolence • Nausea • Ataxia • Impaired vision
- 15. Gabapentin Indication • Second-line treatment for focal seizures • Peripheral (poly)neuropathy • Post-herpetic neuralgia Adverse effects • Somnolence • Nausea • Ataxia • Dry mouth
- 16. Topiramate Indication • Focal and generalized tonic-clonic epileptic seizures • Migraine prophylaxis • Idiopathic intracranial hypertension Adverse effects • Glaucoma • Weight loss • Kidney stones • Cognitive dysfunction (e.g., decreased verbal fluency, cognitive speed, and working memory) • Sedation
- 19. Antiepileptic during pregnency The Best medication to use in pregnency is either levetiracetam or lamotrigine
- 20. Nonpharmacological therapy Indications: pharmaco-resistant epilepsy Surgery • Procedures • Resection (surgical removal of pathological lesions) • Resection of the anteromedial temporal lobe or of the amygdala and the hippocampus in patients with temporal lobe epilepsy, e.g., due to hippocampal sclerosis • Resection of an entire hemisphere (hemispherectomy) in patients with severe intractable seizures due to structural cerebral abnormalities confined to one hemisphere • Disconnection (surgical section of neuronal circuits) • Callosotomy: section of the corpus callosum Initially, partial disconnection only (usually the anterior ⅔) • Complete disconnection if seizures persist • Hemispherotomy: disconnection of the cortex of one hemisphere from the ipsilateral subcortical structures and the cortex of the other hemisphere without removal of the affected hemisphere • Stimulation techniques: vagus nerve stimulation, deep brain stimulation Dietary measures: ketogenic diet
- 22. STATUS EPILEPTICUS Status epilepticus is a seizure that lasts ≥ 5 minutes or a series of seizures in rapid succession without full neurological recovery in the interictal period, which increases the risk of long-term consequences such as neuronal injury and functional deficits. • The time threshold after which a seizure is considered status epilepticus differs according to the type of seizure: • Tonic-clonic seizures: ≥ 5 minutes • Focal seizures with impaired consciousness: ≥ 10 minutes • Absence seizures: 10–15 minutes Etiology • Withdrawal from antiepileptic drugs • Electrolyte imbalance (e.g., hyponatremia, hypocalcemia) • Metabolic disturbances (e.g., hypoglycemia, uremia, porphyria) • Structural brain lesions and/or injury (e.g., tumors, trauma, stroke) • Anoxic brain injury • Alcohol withdrawal • Recreational drug use • Drug toxicity (e.g., from tricyclic antidepressants, isoniazid) • CNS infections (e.g., cerebral malaria, neurocysticercosis, viral encephalitis, prion diseases) • Late-stage neurodegenerative diseases (e.g., Alzheimer disease)
- 23. Classification • With prominent motor features • Convulsive (tonic-clonic) • Myoclonic (with or without coma) • Focal motor • Tonic • Hyperkinetic EEG. diagnostic
- 25. References • 1.Katzung B,Trevor A. Basic and Clinical Pharmacology. McGraw-Hill Education; • 2.Glauser T, Shinnar S, Gloss D, et al. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Currents. 2016; 16(1): p.48-61. doi: 10.5698/1535-7597-16.1.48.| Open in Read by QxMD • 3.Wen X, Wang J-S, Kivistö KT, Neuvonen PJ, Backman JT. In vitro evaluation of valproic acid as an inhibitor of human cytochrome P450 isoforms: preferential inhibition of cytochrome P450 2C9 (CYP2C9). Br J Clin Pharmacol. 2001; 52(5): p.547-553. doi: 10.1046/j.0306-5251.2001.01474.x.| Open in Read by QxMD • 4.Goldenberg MM. Overview of drugs used for epilepsy and seizures: etiology, diagnosis, and treatment.. P & T : a peer-reviewed journal for formulary management. 2010; 35(7): p.392-415. pmid: 20689626. | Open in Read by QxMD • 5.Zhang Y-X, Shen C-H, Lai Q-L, et al. Effects of antiepileptic drug on thyroid hormones in patients with epilepsy: A meta-analysis. Seizure. 2016; 35: p.72- 79. doi: 10.1016/j.seizure.2016.01.010.| Open in Read by QxMD • 6.Le T, Bhushan V, Sochat M, Chavda Y. First Aid for the USMLE Step 1 2017. McGraw-Hill Education; 2017 • 7.Schmidt D, Schachter SC. Drug treatment of epilepsy in adults. BMJ. 2014; 348(feb28 2): p.g254-g254. doi: 10.1136/bmj.g254.| Open in Read by QxMD • 8.Tomson T, Battino D, Bromley R, et al. Executive Summary: Management of epilepsy in pregnancy: A report from the International League Against Epilepsy Task Force on Women and Pregnancy. Epilepsia. 2019; 60(12): p.2343-2345. doi: 10.1111/epi.16395.| Open in Read by QxMD • 9.Karow T, Lang-Roth R. Allgemeine und Spezielle Pharmakologie und Toxikologie. Dr. med. Thomas Karow (2012 und 2013); 2010 • 10.Lüllmann H, Mohr K, Wehling M. Pharmakologie und Toxikologie. Thieme Verlag (2002); 2003 • 11.Karow T, Lang-Roth R. Pharmakologie und Toxikologie. ; 2012