Antiepileptic Drugs Atma Ram Bansal, Arun Garg
INDEX
Page numbers followed by f refer to figure, fc refer to flowchart, and t refer to table.
A
Acetazolamide 110
Acidosis, metabolic 137
Alcohol withdrawal 145
Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 111
American Academy of Neurology 109
American Epilepsy Society 109
Amiodarone 95
Amnesia, transient global 72, 75
Anticonvulsant Drug Development Program 5
Antidepressants, tricyclic 97
Antiepileptic drugs 1, 7, 7t, 8, 8t, 19t, 25, 39, 50, 60, 63, 64t, 69, 71, 73t, 82, 83, 85t, 87, 87t, 88t, 93, 95, 98, 101, 102, 105, 106, 108, 110, 111, 113t, 115t, 116, 117t, 119t, 125, 127t, 128, 142, 149, 150
adverse effects of 20t
approximate cost of 119f
broad and narrow spectrum 111t
choice of 103, 118t
effects of 74t, 118f
first-generation 7
interactions 120t
level monitoring 89
mechanism of action of 41f, 110t
optimal dosage of 116t
pharmacokinetic properties of 18, 20t
pharmacology of 7
polytherapy 108, 109, 112, 116, 119
drawbacks of 121
rational combination of 108
second-generation 7
selection of 78t
side effects of 18
therapy 60
third-generation 7, 50
treatment 104
use of 82, 93
year of discovery 1t, 2f
Antihypertensive 95
Anxiety 78, 118
Apoptosis, induction of 87
Arrhythmias 140
cardiac 94, 118
embryonic cardiac 87
Ataxia 41, 43, 55
Attention deficit disorder 118
B
Barbiturates 110
Benign childhood
epilepsy with centrotemporal spikes 60
seizure susceptibility syndrome 60
Benzodiazepines 11, 38, 94, 110, 113, 115, 118
Beta-blockers 95
Bipolar disorder 78
Blocks synaptic gamma-aminobutyric acid reuptake 110
Blood
brain barrier 6
spots 129
Bones 31
mineral density 74
Bradycardia 28
Brain
magnetic resonance imaging of 68
tumor 106
Breast milk 88, 88t
Breastfeeding 37, 88
Brivaracetam 7, 1820, 40, 50, 52, 52f, 53
Bromide 1, 7
Bupropion 97
C
Calcium 134
calmodulin protein phosphorylation 9
channel 113
actions 8
blockers 110
Cancer 78
Cannabidiol 67
Cannabis sativa, nonpsychotropic compound of 67
Carbamazepine 1, 7, 10, 19, 20, 25, 26, 35, 39, 50, 61, 64, 73, 74, 77, 78, 82, 85, 88, 94, 101, 103, 110, 111, 113, 115120, 126, 127
mechanism of action of 27f
Carbonic anhydrase inhibition 110
Cardiac arrest 140
Cardiac defects 85
Cardiac failure 137
Cardiovascular disease 93
Cardiovascular system 36
Central nervous system 141
Cerebral
abscess 147
damage, seizure induced 140
edema 140
venous sinus thrombosis 140
Chlorpromazine 97
Cleft lip 85
Clobazam 7, 11, 19, 20, 40, 44, 45, 57, 64, 66, 103, 111, 118, 119
Clomipramine 97
Clonazepam 7, 11, 62, 64, 101, 103, 116
Clozapine 97
Congenital malformation, risk of 84, 85, 85t
Contraception 82
Conventional antiepileptic drugs, era of 3
Convulsive movements 144
Cortical venous sinus thrombosis 147
Cough syncope 144
D
Deep brain stimulation 69
Deep venous thrombosis 139
Dehydration 140
Dementia 2, 74, 78
Depression 78, 118
Diazepam 1, 7
Digestive system 37
Digital hypoplasia 85
Digoxin 95
Dihydropyridine 95
Diphenylhydantoin 9
Diplopia 41, 43, 55
Disseminated intravascular coagulation 140
Diuretics 95
Divalproate 118
Dizziness 17, 41, 43, 51, 55
Doose syndrome 63
Dravet syndrome 63, 149
Drop attacks 104
Drowsiness 55
Drug
concentration 37
interactions 28, 31, 38
E
Electrical stimulation techniques 139
Electroencephalogram 61, 133, 135
abnormal 148
Electroencephalography 75, 102, 143
Electrolyte imbalance 140
Encephalopathy
early myoclonic 149
hypoxic-ischemic 67
metabolic 72
Epilepsy 1, 5, 25, 60, 62, 82, 84, 93, 98, 101, 108, 145, 148
benign 60
burden of 71
childhood absence 60, 61, 149
death in 94
early-onset benign childhood occipital 60
focal 148
symptomatic 62
hysterical 2
idiopathic generalized 62
juvenile absence 62, 149
juvenile myoclonic 62, 145, 149
late-onset childhood occipital 60
longer duration of 148
maintenance dose for 28, 30
management of 103, 108
migrating partial 149
pharmacodependent 62
pharmacoresistant 62
pseudorefractory 115
severe myoclonic 67, 149
surgery 69, 109
syndrome 148, 149, 149t
febrile illness-related 141
treatment of 72, 102
Epileptic encephalopathy 62, 63
syndromes 63
Eslicarbazepine 1, 7, 15, 19, 20, 50, 54, 55, 110, 111
acetate 51f, 54
Ethosuximide 1, 7, 16, 25, 26, 33, 34, 61, 65, 74, 78, 103, 110, 111, 113, 115
mechanism of action of 34f
European Medicines Agency 129
Ezogabine 7
F
Fatigue 17, 41, 51
Febrile convulsion 147
Felbamate 1, 7, 74, 110, 113, 115, 118, 126
Fetal
hydantoin syndrome 31, 87
phenobarbitone syndrome 87
syndromes 87t
valproate syndrome 87
First-line antiepileptic drugs
dose of 26t
half-life of 26t
mechanism of action of 26t
therapeutic plasma level of 26t
Fixed dose titration 116
Flexible dose titration 116
Fluoxetine 97
Folate deficiency 87
Food and Drug Administration 56, 63, 98, 108
Fosphenytoin 32, 94, 136
Fractures 140
G
GABAergic drugs 110
Gabapentin 1, 7, 16, 40, 47, 74, 77, 78, 98, 110, 113, 115, 117, 120, 128
Gamma-aminobutyric acid 8, 26, 43, 52, 111, 135
receptors 113
synapse 113
transaminase, inhibits 110
Gastaut, idiopathic childhood occipital epilepsy of 149
Genitourinary system 37
Glandular hypospadias 84
Glucose transporter type 1 deficiency syndrome 69
Glucuronidation 73
Glutamate
blockade 8
decarboxylase 10
receptor 6, 113
H
Hair loss 10
Haloperidol 97
Head injury
mild-to-moderate 147
severe 147
Headache 17, 41, 51, 55, 78, 118
Head-up tilt table test 75
Hemopoietic system 36
Hemorrhagic disease 89
Hepatic enzyme systems 73t, 74t
Hepatic failure, acute 140
High voltage activated channel 110
Hormone, adrenocorticotropic 69
Hyperpyrexia 140
Hypertension 140
Hypertrichosis 31
Hypocalcemia 67, 145
Hypoglycemia 67, 145
Hypomagnesemia 67
Hyponatremia 15, 37, 55, 78
Hypospadias 85
Hypotension 28, 94, 140
Hypothermia 139
I
Immune system 31
Immunotherapy 139
Indian Epilepsy Society 103
Injury 146
Insulin resistance 10
Intensive care unit 133, 135
International League Against Epilepsy 126, 132
Intracerebral bleed 147
J
Jeavons syndrome 149
K
Ketamine infusion 138
Ketogenic diet 39, 139
Kidney disease 30
L
Lacosamide 1, 7, 15, 19, 20, 40, 50, 51f, 53, 54, 94, 103, 110, 111, 113, 118, 119, 127, 136
Lactation 82
Lamotrigine 1, 5, 7, 13, 19, 20, 38, 40, 42, 65, 73, 74, 77, 78, 85, 86, 88, 90, 94, 103, 110, 111, 114120, 127
Landau–Kleffner syndrome 63
Lennox–Gastaut syndrome 42, 63, 149
Lethargy 17
Levetiracetam 1, 7, 12, 19, 20, 40, 45, 46, 52, 64, 77, 78, 85, 94, 103, 110, 111, 114120, 127, 128, 136
Licarbazepine 39
Liver 37
disease 30, 94
function test 37, 55
Lorazepam 12
Losartan 95
Low voltage activated channel 110
M
Magnesium 134
infusion 139
Magnetic stimulation techniques 139
Memory disturbance 2
Meningoencephalitis 147
Menstrual irregularity 10
Mental retardation, presence of 149
Metabolic disorders 147
Metabolites, serum concentrations of 129
Micturition syncope 144
Midazolam 12, 137
Migraine 78
Monitoring plasma concentrations 30
Monoamine oxidase inhibitor therapy 37
Monohydroxy derivative 39
Monotherapy 105, 122
Mood disorders 118
Multiple seizure types 149
N
National Institute of Neurological Disorders and Stroke 5
Nausea 41, 43, 51, 55
N-benzyl-2-acetamido-3-methoxypropionamide 6
Neonatal bleeding, risk of 89
Neural tube defects 83, 85
Neuralgia, trigeminal 30
Neurotransmitter gamma-aminobutyric acid, inhibitory 25
Neutropenia 57, 78
Newer antiepileptic drugs 12, 39, 76
advantages of 77t
disadvantages of 77t
era of 5
mechanism of action of 40t
N-methyl-D-aspartate 111, 136
glutamate receptor 43
N-methyl-D-aspartic acid 111
Noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid 50
Nonepileptic attack disorder 143
O
Obesity 78, 118
Ohtahara syndrome 149
Olanzapine 97
Older antiepileptic drugs 25, 76, 113
advantages of 77t
disadvantages of 77t
Oral contraceptive pills 38
Osteoporosis 78
Oxcarbazepine 1, 7, 15, 19, 20, 3941, 54, 64, 73, 74, 77, 78, 82, 88, 94, 103, 110, 111, 114120
active metabolite of 73
P
Panayiotopoulos syndrome 149
Parasitic granuloma 147
Paroxetine 97
Pentylenetetrazole 4
Perampanel 1, 7, 17, 19, 20, 40, 50, 51, 51f, 103, 127
Pharmacokinetics, age-related 72
Phenobarbital 25, 26, 73, 74, 77, 78, 94, 113, 115, 116, 118, 119, 126, 127
mechanism of action of 27f
Phenobarbitone 1, 7, 8, 19, 20, 64, 82, 85, 88, 101, 103, 118, 136
accidental discovery of 3
antiepileptic properties of 3
Phenytoin 1, 7, 9, 19, 20, 25, 26, 29, 31, 38, 39, 50, 64, 67, 73, 74, 77, 78, 82, 85, 88, 9395, 101, 103, 104, 110, 111, 113, 115120, 126, 127, 136
mechanism of action of 27f
Plasma
drug concentrations 32
protein binding 9, 12
Polycystic ovarian disease 10
Polytherapy 69, 109, 111, 112
effects of 111
potential adverse effects of 120
Porphyria 98
Potassium 134
channel activity 8
Prednisolone 68
Pregabalin 1, 7, 17, 48, 74, 77, 78, 110, 111, 114, 117, 120, 128
Pregnancy 31, 37, 82, 83
implications 28
Primidone 7, 57, 88, 101, 113
Propofol 137
infusion syndrome 137
Pseudoseizure 143, 144, 144t
Psychiatric disorders 96
Psychosis 2, 118
Pyridoxine 139
Q
Quetiapine 97
R
Radial aplasia 85
Raised intracranial pressure 140
Randomized controlled trials 119
Rapid eye movement 72
Rasmussen encephalitis 149
Rational polytherapy 105, 109
Renal disease 96
Renal failure 37, 137, 140
Renal stones 78
Respiratory failure 140
Restless legs 78
Retigabine 7, 17
Rhabdomyolysis 137, 140
Risperidone 97
Rolandic epilepsy 60
Rufinamide 1, 7, 17, 19, 20, 40, 50, 51f, 56, 65, 67, 110, 111, 114, 118
S
Salicylates 95
Saliva concentrations 129
Schizophrenia 2
Sedation 41, 43
Seizure 30, 67, 136, 142, 143, 143t, 144, 150
absence 37
acute symptomatic 146
adverse effects of 83
atonic 37
complex febrile 148
feneralized tonic-clonic 42, 61, 149
focal 75, 103
frequency 83
generalized absence 103
impact of 74
myoclonic 11, 37, 103, 104
primary generalized tonic-clonic 103, 104
risk of 145
single 144, 146
true 144t
type of 72, 103, 103t
Selective serotonin reuptake inhibitors 97
Sertraline 97
Skin 36
Sleep disturbances 118
Sodium 134
channel 113
actions 8
blockers 110
valproate 7, 10, 61, 77, 85, 101, 103, 104, 110, 111, 115, 127
Spina bifida 85
Status epilepticus 27, 28, 30, 132, 133
complications of 140
management of 132, 133, 135, 135fc, 136, 140
new-onset refractory 140
nonconvulsive 76, 133
refractory 133, 137
super-refractory 133, 138
Steripentol 51f
Stevens–Johnson syndrome 31
Stiripentol 7, 18, 50, 56, 65, 126
inhibits 57
Stokes–Adams syndrome 30
Stroke 72
ischemic 147
Succinimides
dose-related side effects of 34
mechanism of action of 33
Sudden unexpected death 84, 146
Sulfonamide 14
Syncope 28, 72, 143, 143t
Syndrome of inappropriate secretion of antidiuretic hormone 37
T
Teratogen 31
Thalidomide disaster 4
Theophylline 38
Therapeutic drug monitoring 125, 127, 128fc
implementation of 127
overuse of 130
Thiopentone 138
Thioridazine 97
Thrombocytopenia 57, 78
Thyroid disease 98
Tiagabine 1, 7, 18, 77, 96, 114116, 128
Ticlopidine 95
Topiramate 1, 5, 7, 13, 19, 20, 40, 43, 44, 65, 73, 74, 77, 78, 85, 88, 103, 110, 111, 114120, 127
Toxic disorders 147
Toxic reactive intermediaries, formation of 87
Transient ischemic attacks 72
Trazodone 97
Tremor 10, 43
Tuberculoma 147
Tuberous sclerosis complex 68
management of 68
U
Uridine diphosphate glucuronosyltransferases 32, 126
V
Vagal nerve stimulation 69, 109
Valproate 1, 19, 20, 61, 73, 74, 78, 94, 95, 113, 116118, 120, 136
Valproic acid 25, 26, 32, 33, 64, 88, 126
mechanism of action of 27f
Venlafaxine 97
Vigabatrin 7, 16, 65, 66, 68, 110, 115, 116, 118
Vision, blurred 41, 55
Vomiting 41, 43
W
Warfarin 38
Weight gain 10, 51
West syndrome 68, 104
management of 68
Z
Zonisamide 1, 5, 7, 14, 19, 20, 40, 46, 65, 66, 73, 74, 77, 78, 88, 103, 110, 111, 114120, 127
×
Chapter Notes

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Antiepileptic Drugs
Antiepileptic Drugs
Editors Arun Garg DM Director Institute of Neurosciences Medanta – The Medicity Gurugram, Haryana, India Atma Ram Bansal DM Senior Consultant Institute of Neurosciences Medanta – The Medicity Gurugram, Haryana, India Foreword Kurupath Radhakrishnan
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Antiepileptic Drugs / Arun Garg, Atma Ram Bansal
First Edition : 2020
9789388958240
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Our neurology team especially Rajeev Goyal, Susant Bhuyan, and Abdul Muniem
FOREWORD
Kurupath Radhakrishnan MD DM FAMS FAAN FANA
Senior Consultant Department of Neurosciences Avitis Institute of Medical Sciences Nemmara, Palakkad, Kerala, India
Former
Director, Department of Neurology and Head R Madhavan Nayar Center for Comprehensive Epilepsy Care Sree Chitra Tirunal Institute of Medical Sciences and Technology Trivandrum, Kerala, India
Head of Department of Neurology, Kasturba Medical College, Manipal Academy of Higher Education Manipal, Karnataka, India
Professor, Department of Neurology, and Head Amrita Advanced Epilepsy Center Amrita Institute of Medical Sciences Cochin, Kerala, India
After making a fairly convincing diagnosis of epileptic seizures, patients are usually initiated on therapy with drugs to control the seizures. Although these drugs help in achieving seizure control in majority of people with epilepsy (PWE) and are therefore very effective antiseizure drugs, there is little evidence to indicate that these drugs influence the process of epileptogenesis [and are therefore truly not antiepileptic drugs (AEDs)]. However, by frequent and prolonged usage, the term “Antiepileptic Drugs”, which the editors have chosen as the title of the book, has become so firmly engraved that it is very difficult to replace it by the more appropriate term “Antiseizure Drugs”.
Over the last three decades, several AEDs have been approved and available for use the world over. Out of the more than 20 AEDs approved, a dozen of them are in common usage today. Although this scenario has made the choice of the AEDs more wide-ranging and evidence-based, it has resulted in widespread misuse of them especially in the developing countries, where majority of PWE are diagnosed and treated by the primary and secondary care physicians who are oblivious of the recent advances in AED therapy.
If correctly chosen and administered, AEDs can result in controlling the seizures in more than two-thirds of PWE. In those who become free of seizures, the AEDs can be tapered and successfully discontinued in the majority in due course of time. However, disappointingly, even today, more than half of the PWE in the community, especially in developing countries, do not receive adequate AED therapy or receive no AED therapy at all. The AEDs not being available and affordable, inability of the primary and secondary care physicians to choose the appropriate AEDs with respect to the type of seizures and epilepsies, myths and misconceptions associated with epilepsy contribute to the treatment gap.
Dr Atma Ram Bansal and Dr Arun Garg have designed this book to address the above-described concerns inherent with the treatment of PWE in developing countries. Through 14 chapters, the book covers every aspect of AEDs including history, pharmacokinetic and pharmacodynamic properties, choice with respect to seizure types and epilepsy syndromes, adverse effects, when to initiate AEDs, and when and how to discontinue them. Additionally, special situations such as AED therapy in status epilepticus and in systemic disorders, in women of the child bearing age and during pregnancy and lactation, and in children and elderly are also deliberated. The authors of each chapter have narrated the topics assigned to them in a comprehensive manner. Several tables and figures strengthen and streamline the text.
Although the editors have primarily intended the book for non-neurologists engaged in treating PWE such as primary and secondary care physicians, pediatricians and psychiatrists, postgraduate students in internal medicine, pediatrics, psychiatry and neurology, and neurologists (both junior and senior, who are not hardcore epileptologists) will also immensely benefit by reading this book. Let me congratulate the authors of individual chapters for the contributions, and the editors for elegantly compiling the chapters. I strongly recommend this book to each and every one involved in the treatment of PWE.
CONTRIBUTORS
EDITORS
CONTRIBUTING AUTHORS
PREFACE
Epilepsy is a well-researched topic with numerous books, monographs, and papers. The numerous literature also shows that there is lot of knowledge that we have acquired, however, lacunae still exist. The effort of this book is to package the best of current knowledge and practices into forming an individualized treatment algorithm. It also covers the diagnostic dilemmas, the myths and misconceptions regarding the disease, and the pros and cons of the antiepileptic drugs (AEDs) in achieving seizure control. The book has contributions from practical wisdom of epilepsy experts. It is a must-have book for any clinician involved in the treatment of epilepsy.
Arun Garg
Atma Ram Bansal