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Introduction Epilepsy is a group is
neurological disorder. An epileptic seizure is a paroxysm(sudden) of uncontrolled discharges of neurons causing an event that is discernible(visible) by the person experiencing the seizures or by the observer. The tendency to have recurrent attacks is known as epilepsy.
Epidemiology Diagnosis is essentially clinically,
relying heavily on eyewitness descriptions of the attacks.
A global campaign has been established to aware about epilepsy, provide information and improve care.
Around 50 million people worldwide have epilepsy.
Nearly 90% of the people with epilepsy are found in developing regions.
Epilepsy ressponds to treatment 70% of the time.
Upto 5% of people will suffer at least one seizure in their lifetime.
Aetiology Epileptic seizures are produced by abnormal
discharges of neurons that may be caused by any pathological process which affects the cortical layer of the brain
causes of epilepsy
symptomatic
idiopathic
cryptogenic
SYMPTOMATIC EPILEPSY: Epilepsy is called symptomatic when it has a known cause.
IDIOPATHIC EPILEPSY: where no apparent cause for epilepsy can be found, but there may be a family history, suggesting that the condition is inherited
CRYPTOGENIC EPILEPSY: This is when the cause for a person's epilepsy has not yet been found, despite investigations
PathophysiologyIN NORMAL CASE :
NEUROTRANSMITTER
S
EXCITATORY
EXCITE NEURON
INHIBITORY INHIBIT NEURON
IN CASE OF EPILEPSY :
DAMAGED OF NEURON
CHANGES IN DISCHARGE
PATTERN
PERIOD OF INACTIVITY (EPILEPSY)
Generalized seizuresGeneralized seizures result in impairment of consciousness from the on set TYPES OF GENERALIZED SEIZURES:There are various types of generalized seizures• Tonic clonic convulsions• Absence attack• Myoclonic seizures• Atonic seizures
MYOCLONIC SEIZURES:In myoclonic seizures very brief involuntary shock like jerks which may involve in the whole body or arms or head usually Happen in morning they may cause person fall.ATONIC SEIZURES:These comprise a sudden loss of muscles tone causing
person to collapse to the ground recovery after ward is quick much commonin pateint with severe epilepsy starting in infancy
TONIC CLONIC SEIZURES:Often called “grand mal” attacks with out warning
the patient suddenly goes stiff,fall,tongue bitting with laboured breathing and salivation it over come after few minutes
ABSENCE ATTACKS:Aften called “petit mal” these are much rarer form it happen in child hood ,child goes bland and stares fluttering of eyelids and flopping of head mayoccur it last only few seconds and un recognized
even by child experencingthem
PARTIAL OR FOCAL SEIZURES SIMPLE PARTIAL SEIZURES: Discharge remains localized &
consciousness is fully preserved.EXAMPLES: Localized jerking of a limb or face,
stiffness or twitching of one part of the body, numbness or abnormal sensations.
COMPLEX PARTIAL SEIZURES: Seizure progresses with
impairment of consciousness. Originate in the frontal or
temporal lobes of the brain and can progress to secondarily generalized seizures.
EXAMPLES: Lip smacking , undressing,
performing aimless activities, acting in a confused manner.
SECONDARILY GENERALISED SEIZURES:
These are partial seizures, either simple or complex.
Discharge spreads to the entire brain.
ECG can demonstrate the partial nature of the seizure.
Involvement of the entire brain leads to a convulsive attack with same characteristics as a generalized tonic clonic convulsion.
DIAGNOSIS Diagnosis of epilepsy is clinical
& depends on a reliable account of what happened during the attacks.
Epilepsy must only be diagnosed when seizures occur spontaneously and are recurrent.
EEG (electroencephalogram) is the only examination required, particularly in generalized epilepsies & aims to record abnormal neuronal discharges.
Magnetic resonance imaging (MRI) is the most valuable investigation when structural abnormalities such as stroke, tumor, congenital abnormalities are suspected.
MRI to be used in people who develop epilepsy as adults or in whom seizures persist or when a structural lesion on the brain may be responsible for seizures.
Treatment National Institute for Health and
Clinical Excellence issued guidance on the treatment of the epilepsies in adults and children in primary and secondary care.
Treatment individualised according to seizure type, epilepsy syndrome, co-medication and co-morbidity, the individual's lifestyle and personal preference.
Treatment during seizures
Made the patient as comfortable as possible ( lying down, cushioning the head, loosening any tight clothing or neckwear)
Should not be moved unless they are in a dangerous place (road, fire, top of stairs, edge of water)
No attempt should be made to open a person’s mouth or don’t force any thing between the teeth
When seizure stops, turned over to recovery phase and check air ways for any blockage
No drinks or extra anti-epileptic drugs required. If seizure persist for more than 10min, IV or Rectal
diazepam(10-20mg) in adults can be given. Lower doses of diazepam advisable for children.
Status epilepticus Initially: Positioning the person to avoid
injury Supporting respiration Maintaining Blood Pressure Correcting hypoglycemia Drugs: DOC= Lorazepam or diazepam
IV Alternative= midazolam
Febrile convulsions Convulsions associated with fever May occur in young Aim to reduce the temperature Use of paracetamol is usual If Prolonged febrile convulsions, DOC is
Diazepam. (IV or PR)
Long term treatment
Long term and regular drug therapy of epilepsy usually for atleast 3 years or for life time
Objective: Suppress epileptic discharges Prevent the development of epileptic seizures Treatment is initiated by specialist only with consideration of
all relevant factors. AED treatment may fails unless the patient fully understands
the importance of regular therapy and the objectives of treatment.
Poor adherence is still a major factor lead to hospitalization and poor seizure control and lead to clinical use of multiple AED.
General principle of treatment Therapy aims to control
seizures using one drug with the lowest possible dose that cause the fewest side effects possible.
The choice of drugs depends largely on the seizure type, and so correct diagnosis and classification are essential.
Initiation of therapy in newly diagnosed patients The first line AED most suitable for the
person’s seizure type should be introduced slowly, starting with a small dose.
This is because too rapid an introduction may include side-effects that will lose the patient’s confidence.
Maintenance dosage
There is no single optimum dose of AED Dose varies from person to person and drug to drug. Drug should be introduce slowly and then increased
incrementally to an initial maintenance dosage. Seizure control then be assessed and the dose of
rug changed if necessary. Most specialists prefer people to remain on the
same brand of medication, and this is also preferred by the majority of people with epilepsy.
Altering drug regimens
Replacement of first drug with another first-line AED.
Example: Lorazepam or diazepam
Alternative: Midazolam
Withdrawal of drugs
AEDS shuoldn’t be withdrawn abruptly
Particularlt with barbiturates & benzodiazepines rebound seizures may occur.Examples: phenobarbital & primidone clobazam & clonazepam
Withdrawal should be carried out in slow step-wise fashion
To cover withdrawal phase benzodiazepine like diazepam can be used
Example of withdrawal regimensCARBAMAZEPINE:100 - 200 mg every 2 weeks100 - 200 mg every 4 weeks
Newer AEDsGenerally used as second-line agents
Guidance has been issued by National Institute for Health & Clinical Excellence for the following:1 USE OF NEWER AEDS IN ADULTS2 USE OF NEWER AEDS IN CHILDREN3 FOR THE DIAGNOSIS & MANAGEMENT OF EPILEPSIES IN ADULTS & CHILDREN IN PRIMARY & SECONDARY CARE
Follow-up and monitoring of treatment
It is essential to follow up patients in whom AED treatment has been started
Monitornig the efficacy and side effects of treatment upon which drug drug dosage will depend
This follow up is particularly important in early stages of treatment
Stopping treatment With drawl therapy is an individual one and
the person shouldbe made aware of the risk and benefits of withdrawl
Drug withdrawl should be carried out only very slowly in staged decrements and only one drug at a time should be withdrawn
Withdrawn therapy should be considered in people who have been free seizure free for a considerable period of time
Monitoring antiepileptic therapy TDM involves the measurement of serum drug s
and their pharmacokinetics interpretation .TDM may be useful to establish adherence with the treatment
At the onset of action If seizure control is poor or sudden changes in
seizure control occur If toxicity is suspected When changes AED therapy or making changes to
other aspects of a persons drug regimen that may interact with the AED
Drug development and action Established AEDs such as
phenytoin,phenobarbital,sodium valporate ,carbamazepine,clonazepam and diazepam
New drugs include lamotrigine,pregabalin,felbamate,zonisamide
Unlike most older agents vigabatrin,zonisamide.lacosamide
1. CARBAMAZAPINE Carbamazepine is a dibenzapine derivative
with antiepileptic and anticonvulsant properties.
Pharmacodynamics: Na-Channel AntagonistIndications: Aggression Diabetes insipidus Epilepsy Mood disorder Trigeminal neuralgia Prophylaxis of bipolar disorder.
Contra-indications:o Bone marrow depressiono Porphyriaso Av conduction abnormalities.Adverse Drug Reaction: o Proteinuriao Skin rasheso Stevens johnson syndromeo Hyponatremiao Agranulocytosiso HematuriaDrug Interaction:o Amitriptylineo Chloroquineo Bromazepamo Fluoxetineo Diltiazem
2. CLONAZEPAM Clonazepam is a benzodiazipine. Benzdiazipines are the most widely used
anxiolytic drugs. Pharmacodynamics: Chloride Channel
Potentiater (GABA operated) Indications: Atypical absence Bipolar affective disorder Drug induced dyskinesias
Contra-indications: Respiratory depression Acute pulmonary insufficiency HypersensitivityAdverse Drug Reaction: Thrombocytopenia Blood dyscrasias Apnea Hypotension, Dizziness, Drowsiness, Fatigue, Anorexia, Drug Interactions: o Alcoholo Carbamazepineo Iproniazid Phosphateo Phenobarbitoneo Valproic Acid
3. ETHOSUXIMIDE Ethosuximide is antiepileptic agent. its popularity continues, based on its
safety and efficacy.Pharmacodynamics: PyrrolidinedioneIndications: Generalised epilepsy with absence
seizures.
Contra-indications: Hypersensitivity to any component of product.Adverse Drug Reaction: Tonic-clonic seizures Nausea Vomiting Anorexia GI symptoms,Drug Interactions:o Alcohol,o Carbamazepineo Isoniazido Phenobarbitoneo Phenytoin (Na), Sodium Valproate
4. LAMOTRIGINE Lamotrigine is a triazine derivarive. Lamotrigine is oral antiepileptic and
anticonvulsant agent.Pharmacodynamics: Triazine DerivativesIndications: o Bipolar disorderso Epilepsy Partial seizureso Tonic-clonic seizureso Generalised epilepsy with absence seizures
Contra-indications: Renal failure Hepatic failure Hypersensitivity.Adverse Drug Reaction: Ataxia Thrombocytopenia Stevens johnson syndrome Angioedema Nystagmus, Extrapyramidal symptoms TremorsDrug Interactions: Carbamazepine Fosphenytoin Phenobarbitone Phenytoin (Na)
5. Phenobarbitone Phenobarbitone is oral and parenteral barbiturate with
anticonvulsant and sedative-hypnotic properties. Phenobarbitone is also the longest-acting agent in the
barbiturate group. Pharmacodynamics: Chloride Channel opener (Gaba
operated) Indications: Benign febrile convulsions of infancy Seizures Short-term treatment of severe congestive heart
failure Status epilepticus.
Contra-indications: Porphyrias Hepatic disease.Adverse Drug Reaction: Ataxia Confusion Irritability Mental disturbances Aplastic Anemia HepatitisDrug Interactions: Alcohol Chlorpropamide Clonazepam Diltiazem (HCl) Ritonavir Verapamil (HCl) Vitamin K, Warfarin (Na
6: LEVETIRACETAM Levetiracetam is an anti epileptic pyrrolidone derivative. Pharmacodynamic:The exact mechanism by which levetiracetam acts
to treat epilepsy is unknown. However, the drug binds to a synaptic vesicle glycoprotein, SV2A.
Indications:Levetiracetam is an anti-epileptic drug which is used for the adjunctive treatment of partial seizures, with or without secondary generalisation.
alternative drug of choice in Iron deficiency anaemia. Contra-indications: Breast feeding Adverse Drug Reaction:Dizziness, Vertigo, Headache, Drowsiness,
Ataxia, Anorexia, Nervousness, Rashes, Depression, Tremor, Asthenia, Aggression.
Drug interactions:phenytoin, phenobarbital, primidone, carbamazepine, valproic acid, lamotrigine, gabapentin, digoxin, oral contraceptives ethinylestradiol, and warfarin
7. OXACARBAZEPINE Oxacarbazepine is an antiepileptic and anti convulsant
drug. Pharmacodynamic:blockade of voltagesensitive sodium
channels could contribute to the antiepileptic efficacy of OCBZ. Indications:adjunctive treatment of partial seizures with or without secondary
generalised tonic-clonic seizures. Contra-indications: Oxcarbazepine is contraindicated in
conditions like Hypersensitivity to any component of product Adverse Drug Reaction:Dizziness, Vertigo, Headache,
Drowsiness, Ataxia, Alopecia, Diarrhea, Constipation, Abdominal pain, Rashes, Confusion, Urticaria, Depression, Tremor, Diplopia,nausea,vomiting.
Drug Interactions: Amiodarone, Amlodipine, Felodipine, Nifedipine, Nimodipine, Verapamil
(Calan, Covera, Isoptin, Verelan) Cyclosporine Lansoprazole (Prevacid) Omeprazole (Prilosec)
8. PHENYTOIN Phenytoin exerts its anticonvulsant effect mainly by limiting
the spread of seizure activity and reducing seizure propagation.
Pharmacodynamics: Na-Channel Antagonist Indications:Convulsions, Epilepsy, Migraine prophylaxis,
Myotonia, Prophylaxis of epilepsy, Status epilepticus, Status epilepticus; seizures in neurosurgery, TIC douloureaux, Ventricular arrhythmias.
Contra-indications: conditions like Porphyrias. Adverse Drug Reaction:Ataxia, Nausea, Vomiting,
Hypotension, Drowsiness, Nystagmus, Coma, Hyperglycemia, Stupor, Blurred vision.
Drug Interactions:Alprazolam, Amiodarone (HCl), Amitriptyline (HCl),Amlodipine, Ciprofloxacin, Clarithromycin,carbamazepine.
9. Sodium Valproate Sodium Valproate is anticonvulsant drug Pharmacodynamics: Na-Channel Antagonist. Indications: Sodium Valproate is primarily indicated in
conditions like All forms of epilepsy, Generalised epilepsy with absence seizures, Prophylaxis of febrile convulsion, Prophylaxis of post traumatic epilepsy, Status epilepticus
Contra-indications: pregnancy. Adverse Drug Reaction: Thrombocytopenia, Pancreatitis,
Liver damage, Extrapyrimidal symptoms, Hyperammonemia, Death, Deepening coma, Weight gain, Tremor, Hair loss, GI disorders, Hematological disorder, Leucopenia.
Drug Interactions: Aspirin, Carbamazepine, Erythromycin, Ethosuximide, Fosphenytoin, Lamotrigine, Mefloquine (HCl), Meropenem, Methotrexate, Phenobarbitone, Phenytoin.
10. PRIMIDONE It resembles phenobarbital in its anticonvulsant activity. Primidone is a derivative of barbituric acid.
Pharmacodynamics: work via interactions with voltage-gated sodium channels which inhibit high-frequency repetitive firing of action potentials
Indications: Primidone is primarily indicated in conditions like Epilepsy, Essential tumor.
Contra-indications: Primidone is contraindicated in conditions like Porphyrias.
Adverse Drug Reaction: Vertigo, Ataxia, Nausea, Vomiting, Drowsiness, Sleepiness, Irritability, Ataxia, Tremors, Impotence, Loss of libido, Loss of memory,depression.
Drug Interactions: Acetazolamide (Na), Alcohol, Carbamazepine, Chloramphenicol, Cortisone (Acetate), Desogestrel, Desonide, Estradiol (Valerate), Ethynodiol ,Na valporate.
Conclusion
