Epilepsy and seizures a deep insight- by Rxvichu!!

EPILEPSY AND SEIZURES- A DEEP
INSIGHT
PRESENTED BY:
VISHNU.R.NAIR,
4TH YEAR PHARM.D,
NATIONAL COLLEGE OF PHARMACY,
KERALA UNIVERSITY OF HEALTH SCIENCES(KUHS),

INDEX/CONTENTSOFTHISPPT:
1. GENERAL ACKNOWLEDGEMENT
2. GENERALIZED TERMINOLOGIES
3. EPIDEMIOLOGY
4. TYPES OF EPILEPSIES{INCLUDING CLINICAL
MANIFESTATIONS}
5. ETIOLOGY OF EPILEPSY
6. PATHOPHYSIOLOGY OF EPILEPSY
7. RISK FACTORS FOR SEIZURES
8. DIAGNOSIS OF EPILEPSY
9. MANAGEMENT STRATEGIES FOR EPILEPSY

 GENERAL ACKNOWLEDGEMENT  :
TO THE ALMIGHTY , MY NEAR AND DEAR ONES… AND TO
ALL READERS WORLDWIDE!!!
THANKFUL TO ALL FOR UR SUPPORT, GUIDANCE AND
ENCOURAGEMENT………………
ITS BEEN A REALLY HARD JOB WORKING ON THIS
PPT…………………
HOPE U LIKE IT!!
HAPPY READING!!!
  

 GENERALIZED TERMINOLOGIES  :
1. SEIZURE:
“PHENOMENON, characterized by an EXCESSIVE, HYPERSYNCHRONOUS
DISCHARGE of CORTICAL NEURONAL ACTIVITY, (measured by EEG), featured by
DISTURBANCES in CONSCIOUSNESS, SENSORY MOTOR SYSTEMS, SUBJECTIVE
WELL-BEING and OBJECTIVE BEHAVIOUR…………………”
2. EPILEPSY:
“CHRONIC SEIZURE DISORDER/ GROUP OF DISORDERS, characterized by SEIZURES,
that usually occur UNPREDICTABLY, in the ABSENCE of a SUBSTANTIAL PROVOKING
FACTOR…………….”
3. CONVULSION:
“VIOLENT, INVOLUNTARY CONTRACTIONS of VOLUNTARY MUSCLES, which may/
may not be present in epilepsy/ seizure disorder………..............”

 EPIDEMIOLOGY OF EPILEPSY  :
- Higher risk observed in extremes of age
- Prevalence in European countries is 0.5%
- Prevalence in developing countries is higher, due to parasitic illnesses like
CYSTICERCOSIS
- Around 50 million people worldwide have epilepsy
- Epilepsy responds to treatment in 70% cases
- 75% people in developing countries do not get required anti-epileptic
treatment…………………..

 TYPES OF EPILEPSIES (INCLUDING
CLINICAL MANIFESTATIONS)  :
Based on INTERNATIONAL LEAGUE AGAINST EPILEPSY(ILAE)
classification:
1. PARTIAL SEIZURES (FOCAL SEIZURES)
2. GENERALIZED SEIZURES ………………………………………

1. PARTIAL SEIZURES (FOCAL SEIZURES):
- Most common seizure type
- Localized to a neuronal system, limited to PART OF 1 CEREBRAL HEMISPHERE
- Types include:
A. SIMPLE PARTIAL SEIZURES:
- Not associated with loss of consciousness
- Associated with:
i. MOTOR SIGNS (Convulsive jerking, lip smacking)
ii. SENSORY & SOMATOSENSORY SIGNS (Paresthesias, auras)
iii. AUTONOMIC SIGNS (Sweating, flushing)
iv. BEHAVIOURAL MANIFESTATIONS (Dysphasia, structured hallucinations)

B. COMPLEX PARTIAL SEIZURES:
- Associated with IMPAIRED CONSCIOUSNESS
- Impairment precedes/ follows seizures
- Associated with:
i. Purposeless behavior
ii. Glassy stare
iii. Aimless walking
iv. Hallucinations (visual, auditory)
v. Aggressive behaviour……………………………….

2. GENERALIZED SEIZURES:
- Diffuse seizures
- Affect BOTH CEREBRAL HEMISPHERES
- Types include:
A. IDIOPATHIC EPILEPSIES:
- Age related onset
- Also congenital (genetic origin)
B. SYMPTOMATIC EPILEPSIES:
- Aftermath of a DOCUMENTED UNDERLYING CNS DISORDER
C. CRYPTOGENIC EPILEPSY:
- Cause unknown
- Presumed to be age- related

Manifestations of generalized seizures include:
A. ABSENCE SEIZURES:
- Also known as ‘PETIT MAL’ seizures
- Alterations of consciousness, lasting 10-30 mins. Occurs
- Associated with:
a. Staring, with occasional eye-blinking
b. Enuresis
B. MYOCLONIC SEIZURES:
- Also known as ‘BILATERAL MASSIVE EPILEPTIC MYOCLONUS’
- Associated with INCVOLUNTARY, RHYTHMIC JERKING of FACIAL, LIMB/ TRUNK
MUSCLES
C. CLONIC SEIZURES:
- Associated with SUSTAINED MUSCLE CONTRACTIONS, alternating with
RELAXATION

D. TONIC SEIZURES:
- Associated with SUSTAINED MUSCLE CONTRACTIONS (Stiffening)
E. GENERALIZED TONIC-CLONIC SEIZURES (GTCS):
- Also known as ‘GRAND MAL’ seizures
- Causes sudden loss of consciousness
- Individual becomes rigid and falls to the ground
- Interrupted respirations
- Extended legs
- Lasts for 1 min.
- Rapid bilateral muscle jerking
- Heavy salivation, tongue biting, headache, confusion
- In some cases, GRAND MAL seizures occurs repeatedly, with no recovery of consciousness
between attacks, leading to state known as ‘STATUS EPILEPTICUS’………………..

F. ATONIC SEIZURES:
- Also known as ‘DROP ATTACKS’
- Sudden loss of postural tone  individual falls to the ground
- Occurs mainly in children…………………………………..

 ETIOLOGY OF EPILEPSY  :
Mainly we will see the causes of:
A. FOCAL SEIZURES
B. GENERALIZED SEIZURES…………………………..

1. CAUSES OF FOCAL SEIZURES:
Include:
A. IDIOPATHIC REASONS:
- Benign ROLANDIC epilepsy of childhood (Discovered by Italian Anatomist Luigi Rolando)
- Benign OCCIPITAL epilepsy of childhood
B. GENETIC REASONS:
- Tuberous sclerosis (characterized by tiny benign tumours {angiofibromas} on the face, skin, and
abnormalities of kidney, brain and heart)
- Autosomal dominant frontal lobe epilepsy
- Autosomal dominant partial epilepsy with auditory features (ADPEAF)
- Von Hippel-Lindau disease (characterized by hemangioblastomas {benign blood vessel tumours } in
brain, spinal cord, retina; kidney cysts & cancer and pheochoromocytomas}
- Neurofibromatosis (causes tumours to grow on nerves and inhibits neural growth)
- Cerebral migration abnormalities

C. INFANTILE HEMIPLEGIA (acute hemiparesis, that occurs in infancy, caused
by vascular accidents, like cerebral infarction or thrombosis)
D. DYSEMBRYONIC CAUSES:
- Cortical dysgenesis
- Sturge-Weber syndrome (mainly affects the skin, featured by ‘port wine stain birthmark’;
also known as ‘Encephalotrigeminal angiomatosis’)
E. MESIAL TEMPORAL SEIZURES:
- Associated with febrile convulsions
F. CEREBROVASCULAR DISEASES:
- Intracerebral hemorrhage
- Cerebral infarction
- Arteriovenous malformation
- Cavernous hemangioma (occurs on body surface, as red or purplish, blood filled lakes/
channels)

G. PRIMARY AND SECONDARY TUMOURS
H. TRAUMA (including neurosurgery)
I. INFECTIVE CAUSES:
- Cerebral abscess (pyogenic) - Toxoplasmosis - Cysticercosis - Tuberculoma
- Subdural empyema - Encephalitis - HIV infections
J. INFLAMMATORY CAUSES:
- Sarcoidosis - Vasculitis………………………..

2. CAUSES OF GENERALIZED SEIZURES :
Includes:
A. GENETICS:
- Inborn metabolism errors - Storage diseases - Phacomatoses (Tuberous
sclerosis)
B. CEREBRAL BIRTH INJURY
C. HYDROCEPHALUS
D. CEREBRAL ANOXIA
E. ALCOHOL WITHDRAWAL
F. TOXINS:
- Organophosphates (SARIN)
- Heavy metals (LEAD, TIN)

G. DRUGS:
- ANTIBIOTICS (Penicillin, metronidazole, Isoniazid)
- ANTIMALARIALS (Chloroquine, mefloquine)
- CYCLOSPORINE
- ANTI-ARRRHYTHMICS (Lidocaine, disopyramide)
- PSYCHOTROPICS (Phenothiazines, TCAs, Lithium)
- AMPHETAMINE WITHDRAWAL
H. METABOLIC DISEASE :
- Hypocalcemia
- Hyponatremia
- Hypomagnesemia
- Hypoglycemia
- Renal failure
- Liver failure

I. INFECTIVE CAUSES:
- Post- infective encephalopathy
- Meningitis
J. INFLAMMATORY CAUSES:
- Multiple sclerosis
- SLE
K. DIFFUSE DEGENERATIVE DISEASES:
- Alzheimer’s disease
- CREUTZFELDT- JAKOB DISEASE (Degenerative, invariably fatal brain disorder,
associated with failing memory ,behaviour changes, weakness of extremities, mental
deterioration and coma)……………………………..

 PATHOPHYSIOLOGY OF EPILEPSY 
:1. Neurons are inter-connected in a complex network
2. Each individual neuron  linked via synapses with hundreds of others
3. Neurons  discharge electrical current  neurotransmitters are released at synaptic levels
 permits inter- communication
4. Neurotransmitters are of 2 types:
a. INHIBITORY NEUROTRANSMITTER (GABA):
- GABA (Gamma amino butyric acid )  acts on ion channels  increases chloride inflow
 decreases chances of action potential formation
b. EXCITATORY NEUROTRANSMITTER ( ASPARTATE, GLUTAMATE):
- Above agents  allow sodium and calcium influx  paves way for action potential
formation
5. In this manner, information is conveyed, transmitted and processed throughout the CNS
6. Imbalance between above excitation and inhibition  seizures occur

7. A normal neuron discharges repetitively at LOW BASELINE FREQUENCIES
8. If neurons are damaged, injured/ suffer a chemical/ metabolic insult  changes in discharge
pattern develops
9. During epilepsy  regular low frequency discharges are replaced by BURSTS of HIGH
FREQUENCY DISCHARGES  followed by periods of INACTIVITY
10. A single neuron discharging in an abnormal manner is usually not clinically significant
11. When a WHOLE POPULATION of NEURONS DISCHARGE SYNCHRONOUSLY in an
ABNORMAL MANNER  EPILEPTIC SEIZURE IS PRECIPITATED
12. This abnormal discharge may remain LOCALIZED/ it may SPREAD TO ADJACENT
AREAS, RECRUITING MORE NEURONS as it EXPANDS…………………………….

 RISK FACTORS FOR EPILEPSIES  :
1. Sleep deprivation
2. Missed doses of anti-epileptic drugs(AEDs) in treated patients
3. Alcohol withdrawals
4. Recreational drug misuse
5. Physical and mental exhaustion
6. Flickering lights (includes TV, computer screens; comes under generalized epilepsy
syndrome)
7. Intercurrent infections
8. Metabolic disturbances
9. UNCOMMON REASONS:
- Loud noises
- Very hot baths…………………………………

 DIAGNOSIS OF EPILEPSIES  :
Based on the following criteriae:
1. TO CHECK THE LOCATION OF EPILEPTIC
ORIGIN:
- Standard EEG
- Sleep EEG
- EEG, with special electrodes
2. TO CHECK FOR STRUCTURAL LESIONS:
- CT SCAN - MRI SCAN
3. FOR METABOLIC DISORDER DIAGNOSIS:
- Urea and electrolytes - LFTs
- Blood glucose levels - Serum calcium and magnesium levels

4. FOR INFLAMMATORY/ INFECTIVE DISORDER
DIAGNOSIS:
- CBC - ESR - CRP TEST - CHEST XRAY
- SEROLOGY FOR SYPHILIS, HIV, COLLAGEN DISEASE
- CSF EXAMINATION
5. FOR CONFIRMING ATTACKS TO BE OF EPILEPTIC
ORIGIN:
- Ambulatory EEG - Video telemetry
6. BRAIN IMAGING:
Indicated for:
- Epilepsy starting after 16 yrs. of age
- Seizures, with clinical focal features
- EEG, showing a focal seizure source

 MANAGEMENT OF EPILEPSY  :
 Includes:
1. GOALS OF THERAPY
2. GENERAL GUIDELINES FOR ANTICONVULSANT
THERAPY
3. PHARMACOTHERAPY
4. GUIDELINES FOR CHOICE OF ANTI-EPILEPTIC
DRUGS(AEDs)
5. NON-PHARMACOTHERAPY/ PATIENT- COUNSELLING
TIPS+ HOME REMEDIES FOR EPILEPSY

 1. GOALS OF THERAPY  :
1. To control and reduce SEIZURE FREQUENCY
2. To focus on MINIMUM POSSIBLE DOSAGE OF AEDs
3. To minimize ADRs associated with therapy
4. To ensure PATIENT MEDICATION COMPLIANCE
5. To ensure that person lives a normal life as far as possible
6. To balance COMPLETE SUPPRESSION of SEIZURES against ADR TOLERABILITY
7. To reduce MORBIDITY and MORTALITY
8. To improve QUALITY OF LIFE(QOL)………………………………..

 2. GENERAL GUIDELINES FOR
ANTICONVULSANT THERAPY : 
1. Start with 1 FIRST LINE DRUG
2. Start with a low dose  gradually increase dose until effective control of seizures is
achieved/ ADRs develop
3. Optimize compliance (use minimum no. of doses/ day)
4. If 1st line drug fails (seizures continue/ ADRs develop)  start 2nd (1st line drug) , followed
(if possible) , by gradual withdrawal of the drug presently being used
5. If 2nd line drug fails (due to above reasons)  start 2nd line drug, in combination with
preferred 1st line drug at maximum tolerated doses (keep in mind possible interactions)
6. If above combination fails (due to above reasons)  replace 2nd line drug with alternative
2nd line drug

7. If above combination fails (due to above reasons)  check compliance & reconsider
diagnosis, based on the following criteriae:
a. If the events are seizures/ not
b. Presence absence of occult lesions
c. Treatment compliance/ alcohol/ drugs confounding responses
8. Consider alternative, non-drug treatments, like:
a. Epilepsy surgery
b. Vagal nerve stimulation
9. Use minimum number of drugs in combination at any one time………………………….

 3. PHARMACOTHERAPY : 
A. BARBITURATES :
Include:
I. PHENOBARBITONE (LUMINAL):
- Drug has 3 actions:
a. Drug  depresses sensory, motor cortex and cerebellum
b. Drug  acts on GABA(A) receptors  increases synaptic inhibition  increases seizure
threshold and decreases spread of seizure activity from a seizure focus
c. Drug  inhibits CALCIUM channels  decreases excitatory transmitter release
- ADR :
a. Sedation c. Headache
b. Respiratory depression (when given i.v)

- DRUG INTERACTION:
a. Phenobarbital + oral contraceptives  decreased efficacy of latter
- USES:
a. Febrile convulsions (8 mg/kg/day; child)
b. GTC c. Neonatal seizures d. Status Epilepticus (SE)
B. DEOXYBARBITURATES :
Includes:
I. PRIMIDONE (MYSOLINE):
- MOA:
Drug  enters body  metabolized by liver to PHENOBARBITONE  Shows remaining effects
- ADR:
a. STEVEN-JOHNSON SYNDROME (SJS)
b. Hypotension
c. Hepatitis

- DRUG INTERACTION:
a. BZDs + Drug  increased sedation
- USES:
A. GTCS (250-500 mg BD)
B. Partial epilepsy
C. HYDANTOINS :
Includes:
A. PHENYTOIN (BARBITOIN):
- Drug has 3 actions:
i. Drug  promotes sodium efflux/ decreased sodium influx from membranes in motor
cortex neurons
ii. Drug  stabilizes neuronal membranes
iii. Drug  slows conduction velocity

- ADR:
i. Gingival hyperplasia
ii. Hirsutism
iii. Megaloblastic anemia
iv. Diabetes mellitus
v. FETAL HYDANTOIN SYNDROME (Drug  used in pregnancy  causes hare lips,
microcephaly in neonates etc)
- DRUG INTERACTIONS:
a. Drug + Pyridoxine(in high dose)  decreased levels of phenytoin
- USES:
a. Tonic clonic seizures
b. SE (10-15 mg/kg i.v/ infusion)

B. FOSPHENYTOIN (FOSPHEN):
- MOA:
Drug  converted to PHENYTOIN after injection  shows actions of PHENYTOIN
- ADR:
a. Hypersensitivity b. SJS c. Hepatotoxicity
a. Drug + CBZ(Carbamazepine)  decreased CBZ efficacy
- USES:
a. Seizures, associated with NEUROSURGERY/ HEAD INJURY
b. SE (20 mg/kg i.v)………….

D. IMINOSTILBENES :
Includes:
A. CARBAMAZEPINE (CARBATOL):
- Drug shows 2 actions:
i. Drug  stabilizes inactivated state of sodium channels  makes neurons less excitable
ii. Drug  decreases activity of NUCLEUS VENTRALIS of thalamus / synaptic
transmission associated with neuronal discharge
- ADR:
a. SJS b. Arrhythmia c. CHF
a. Drug + warfarin  decreased anticoagulant effect
- USES :
a. Trigeminal neuralgia c. Epilepsy (200-400 mg TDS)
b. Bipolar disorder

B. OXCARBAZEPINE (CARBOX):
i. Drug  blocks sodium channels  stabilizes neuronal membranes
ii. Drug  inhibits repetitive firing
iii. Drug  reduces synaptic impulse propagation
iv. Drug  increases potassium conductance
v. Drug  modulates activity of high voltage activated calcium channels
- ADR:
a. SJS b. Hepatitis c. Pancreatitis
- DRUG INTERACTION:
a. Furosemide + drug  increased risk of HYPONATREMIA
- USES :
a. Partial seizures , with/ without secondary generalization (in adults: 0.6-2.4 g/day, in divided
doses)……………………

E. SUCCINIMIDES:
Includes:
A. ETHOSUXIMIDE (ZARONTIN):
i. Drug  depresses nerve transmission in motor cortex
ii. Drug  increases convulsive stimuli threshold in CNS
- ADR:
a. GI disturbances b. Dizziness
- DRUG INTERACTION:
a. Drug + sodium oxybate  pharmacodynamic synergism  increased toxicity of each
other  additive CNS depression
- USE:
a. Absence seizures : 500 mg P/O QID…………………….

F. ALIPHATIC CARBOXYLIC ACIDS:
Includes:
I. VALPROIC ACID (VALPROL):
i. Drug  increases GABA levels in brain
ii. Drug  increases / mimics action of GABA at postsynaptic receptor sites
iii. Drug  inhibits sodium and calcium channels
- ADR:
a. SJS b. Pancreatitis c. Thrombocytopenia
- DRUG INTERACTION:
a. Drug + Chlorpromazine  severe HEPATOTOXICITY
- USES:
a. Complex partial seizures (For adults: max. 60 mg/kg/day)
b. Simple and complex absence seizures…………………..

II. DIVALPROEX (DIVAA):
- MOA : Same as that of SODIUM VALPROATE
- ADR:
a. Increased bleeding time
b. Encephalopathy
c. Dementia
- DRUG INTERACTION :
a. Drug + cholestyramine  decreased levels of divalproex
- USES :
a. Complex partial seizures (max.: 60 mg/kg/day)
b. Mania
c. Migraine prophylaxis
d. Simple and complex absence seizures………………………………

G. BENZODIAZEPINES :
Includes:
I. CLONAZEPAM (CLONA):
- Long acting BZD
a. Drug  increases presynaptic GABA inhibition
b. Drug  decreases monosynaptic and polysynaptic reflexes
c. Drug  facilitates GABA neurotransmission and other inhibitory neurotransmitters 
suppresses muscle contractions
- ADR:
a. Blood disorders b. Increased LFTs c. Respiratory depression
- DRUG INTERACTION:
a. Amiodarone + drug  increased drug toxicity

- USES:
a. Panic disorder
b. Seizure disorders (For adult: up to 1.5 g , in 3 divided doses)
c. SE
II. CLOBAZAM (CLOBA):
- 1,5- BENZODIAZEPINE (Contrary to others)
- MOA:
Drug  binds to GABA(A) receptor  potentiates GABA- ergic neurotransmission
- ADR:
a. Hypotension b. Respiratory depression c. Jaundice
- DRUG INTERACTION:
a. CBZ + Clobazam  decreased drug levels
b. Alcohol + Clobazam  increased drug levels

III. DIAZEPAM (DIZEP):
a. Drug  modulates postsynaptic effects of GABA(A) transmission  results in an
increase in presynaptic inhibition
b. Drug  acts on part of limbic system, thalamus and hypothalamus  induces CALMING
EFFECT
- ADR:
a. Respiratory depression
b. Hypotension
c. Jaundice
- DRUG INTERACTION:
a. Hormonal contraceptives + Drug  increased drug effects  increased incidence of
BREATH-THROUGH BLEEDING

- USES:
a. STATUS EPILEPTICUS (Adult: 5-10 mg every 5-10 mins. ; maximum 30 mg.)
b. Anxiety
c. Conscious sedation for procedures
d. Ethanol withdrawal
e. Insomnia associated with anxiety
f. Muscle spasm with tetanus
g. Night terrors
h. Sedation
i. Skeletal muscle relaxation
j. Sleep walking………………………………..

IV. LORAZEPAM (LOPEZ):
- Short onset of effect
- Long half-life
a. Drug  increases action of GABA
b. Drug  depresses all levels of CNS, including lumbar and reticular formation
- ADR:
a. Respiratory depression b. Hypotension c. Jaundice
a. Loxapine + drug  increased respiratory depression
b. Zidovudine + drug  increased headache

- USES:
a. Antiemetic (adjuvant therapy)
b. Acute anxiety
c. Insomnia associated with anxiety
d. Panic disorder
e. Pre-operative medication
f. Sedation
g. SE (For adult: 4 mg; repeat once after 10 mins, if necessary)………………………..

H. PHENYLTRIAZINES:
Includes:
LAMOTRIGINE (LAMORIN):
a. Drug  inhibits release of excitatory amino acids (glutamate)
b. Drug  inhibits voltage sensitive sodium channels  stabilizes neuronal membranes
- ADR:
a. SJS b. DIC c. Lymphadenopathy
- DRUG INTERACTION:
a. Drug + Phenytoin/Phenobarbital  decreases levels of drug
- USES:
a. Bipolar disorder
b. GTC( For adult: 25 mg/day for initial 14 days  then increase dose to 50 mg/day for next
14 days  then increase dose to 50-100 mg/day for next 7-14 days)……………………..

I. CYCLIC GABA ANALOGUES:
Includes:
A. GABAPENTIN (GABAPENTIN):
- Structurally related to GABA, but has no effect on GABA binding, uptake/ degradation
- MOA:
Drug  modulates voltage sensitive calcium channels  decreases entry of calcium into
presynaptic neurons  decreases glutamate release  decreases neuronal excitability
- ADR :
a. SJS b. ARF c. Hepatitis
- DRUG INTERACTION:
a. Drug + phenytoin/antacids decreased levels of latter

- USES:
a. Diabetic neuropathy
b. Focal seizures, with/ without secondary generalization (For child: 12-18 yrs  300 mg
TID/ 0.9-3.6g/day ,in 3 divided doses)
c. Restless legs syndrome
d. Post- therpetic neuralgia / neuropathic pain………………
B. PREGABALIN (PREGALIN):
i. Drug  binds to a subunit of voltage gated calcium channels in CNS  remaining same
as GABAPENTIN
ii. Does not affect sodium channels
- ADR:
a. Primary AV block b. CHF c. SJS

a. Drug + Lorazepam/ alcohol  increased efficacy of latter
- USES:
a. Partial seizures, with/ without secondary generalization (50-300 mg/day, in 2-3 divided
doses, for adults; maximum: 600 mg/day)
b. Anxiety
c. Peripheral and central neuropathic pain
d. Fibromyalgia……………………………..

J. NEWER DRUGS:
Include:
I .TOPIRAMATE
II.ZONISAMIDE
III. LEVETIRACETAM
IV. VIGABATRIN
V. TIAGABINE
VI. LACOSAMIDE
VII. FELBAMATE
VIII. RUFINAMIDE
IX. STIRIPENTOL
X. ESLICARBAZEPINE ACETATE
XI. PERAMPANEL…………………………………..

I. TOPIRAMATE (TOPIRATE):
- CLASS: SULFAMATE SUBSTITUTED DERIVATIVE
a. Drug  inhibits neuronal voltage dependent sodium channels
b. Drug  enhances activity of GABA
- ADR:
a. SJS b. Thrombocytopenia c. Toxic epidermal necrolysis(TEN)
- DRUG INTERACTION:
a. Zonisamide+ drug  increased risk of renal calculi
- USES:
a. Epilepsy (200-1000 mg/day)
b. Migraine prophylaxis
c. Partial seizures……………………………….

II. ZONISAMIDE (ZONICARE):
- CLASS: SULFONAMIDE DERIVATIVE (Benzisoxazole compound)
a. Drug  acts at sodium and calcium channels  stabilizes neuronal membranes
b. Does not affect GABA activity
c. More active against TONIC PHASE than against CLONIC PHASE
- ADR:
a. SJS b. TEN c. Rhabdomyolysis
- DRUG INTERACTION:
a. CBZ+ Zonisamide  decreased level of Zonisamide (by affecting CYP3A4 metabolism)
- USES:
a. Partial seizures, with/ without secondary generalization (300-500 mg/ day; in 1-2 divided
doses)……………………………………..

III. LEVETIRACETAM (LEVACETAM):
- CLASS: PYRROLIDINE DERIVATIVE
a. Drug  inhibits voltage dependent N-TYPE CALCIUM CHANNELS
b. Drug  binds to synaptic proteins  modulate neurotransmitter release
c. Drug  displaces negative modulators  facilitates GABA- ergic inhibitory transmission
- DRUG INTERACTION:
a. CBZ + Drug  CBZ toxicity occurs
- ADR:
a. Thrombocytopenia b. Pancreatitis c. Hepatic dysfunction
- USES:
a. GTC (Max: 1.5 g BID; For adults)
b. Myoclonic seizures
c. Partial seizures, with or without secondary generalization………………….

IV. VIGABATRIN (SABRIL):
- CLASS: GAMMA-VINYL GABA DERIVATIVE
- MOA:
Drug  irreversibly inhibits GABA-transaminase  increases GABA levels in brain
- ADR:
a. Weight gain in children (47%)
b. Permanent bilateral concentric visual field constriction (>30%)
c. Fatigue (28%)
- DRUG INTERACTION:
a. Drug + CLOBAZAM  Increased sedation, respiratory depression
- USES:
a. Complex seizures (1.5 g BID)
b. Partial seizures
c. Infantile spasms
d. Refractory complex seizures………………………….

V. TIAGABINE (GABITRIL):
- CLASS: GABA REUPTAKE INHIBITOR
- MOA:
drug  blocks GABA reuptake by presynaptic neuron  increases its activity in nervous
system
- ADR:
a. Dizziness (26-30%)
b. Asthenia (16-20%)
c. Somnolence (16-20%)
- DRUG INTERACTION:
a. Drug + Clobazam  increased sedation/ respiratory depression
- USES:
a. Partial seizures (with hepatic enzyme inducing anticonvulsants)
b. Partial seizures (without hepatic enzyme inducing anticonvulsants; 12-22 mg/day , divided
in 2-3 doses)…………………………………

VI. LACOSAMIDE (LACOSAM):
- CLASS : HOMOSERINAMIDE DERIVATIVE; FUNTIONAL AMINO ACID
a. Drug  slowly inactivates voltage gated sodium channels
b. Drug  binds to collapsin response mediator protein-2 (CRMP-2); a phosphoprotein;
expressed mainly in nervous system  modulates neuronal differentiation and axonal
outgrowth
- ADR:
a. Dizziness (31%) d. Atrial fibrillation
b. Diplopia (11%) e. Atrial flutter
c. Headache (11%) f. Suicidal ideation
- DRUG INTERACTION:
a. Drug + anti- arrhythmics  enhanced PR-prolongation
- USES:
a. Neuropathic pain b. Partial seizures (200-400 mg/day)…….

VII. FELBAMATE (FELBATOL):
- CLASS : CARBAMATE DERIVATIVE
a. Drug  positive modulator of GABA(A) receptor
b. Drug  blocks NMDA receptors (NR2B subunit)
- ADR:
a. Anorexia
b. Liver failure
c. Aplastic anemia
- DRUG INTERACTION:
a. Felbamate + clopidogrel  decreased effects of clopidogrel
- USES:
a. Partial seizures, with/ without secondary generalization (Adults: 1,200 mg Q6H/Q8H)
b. Partial/ Generalized seizures , associated with LENNOX-GASTAUT SYNDROME …….

VIII. RUFINAMIDE (BANZEL):
- CLASS : TRIAZOLE DERIVATIVE
- MOA:
Drug  modulates activity of sodium channels  prolongs their inactive state  limits
repetitive firing of sodium dependent action potentials  anticonvulsant effect
- ADR:
a. Diplopia
b. SJS
c. Dizziness
- DRUG INTERACTION :
a. Rufinamide + alprazolam  decreased levels/ effects of latter
- USE:
a. LENNOX-GASTAUT SYNDROME (3,200 mg/day maximum, in 2 divided
doses)……………………………..

IX. STIRIPENTOL (DIACOMIT):
- CLASS: AROMATIC ALLYLIC ALCOHOLS
a. Drug  increases GABA transmission
b. Drug  increases duration of opening of GABA(A) receptor channels in hippocampal
areas  enhances central GABA transmission
c. Drug  increases GABA levels in brain tissues by interfering with its uptake &
metabolism
d. Drug  inhibits LACTATE DEHYDROGENASE  Makes neurons less prone to fire
action potentials
e. Drug  improves effectiveness of other anti-convulsants……………
- ADR:
a. Hyperkinesia
b. Drowsiness
c. Ataxia

- DRUG INTERACTION:
a. Drug + CBZ/ Phenobarbital  increased efficacy/ potency of latter
- USES:
a. DRAVET SYNDROME (Along with sodium valproate and Clobazam; 50 mg/kg/day)
b. Epilepsy in infancy
c. Refractory childhood epilepsy( in combination with CBZ)………….
X. ESLICARBAZEPINE ACETATE (ESLIZEN):
- CLASS : DIBENZAPINE CARBOXAMIDE DERIVATIVE
a. PRODRUG  activated to ESLICARBAZEPINE/ S-LICARBAZEPINE (Major active
metabolite of OXCARBAZEPINE)  Blocks sodium channels  inhibits repetitive firing
 decreases synaptic impulse propagation  stabilizes neuronal membranes
b. Drug  increases potassium conductance
c. Drug  modulates activity of high voltage gated activated calcium channels

- ADR:
a. Blurred vision
b. HTN
c. Peripheral edema
- DRUG INTERACTION:
a. Drug + Phenytoin/ Barbiturates  decreased drug levels
- USE:
a. Partial onset seizures (for adult: 400 mg/day; for 7 days)……………….

XI. PERAMPANEL (FYCOMPA):
- CLASS : NON-COMPETITIVE AMPA RECEPTOR ANTAGONIST)
- MOA:
Drug  non- competitively blocks ALPHA-AMINO-3-HYDROXY-5-METHYL-4-
ISOXAZOLEPROPIONIC ACID (AMPA ) glutamate receptor on post synaptic neurons 
decreased glutamate activity  decreases neurological disorders causes by glutamate over-
excitation
- ADR:
a. Dizziness (16-43%)
b. Somnolence (9-18%)
c. Suicidal ideation (notorious)
- DRUG INTERACTION:
a. Drug +CBZ  Decreased perampanel effectiveness
- USES:
a. Partial onset seizures (8-12 mg/day) b. Tonic clonic seizures……………….

 4. GUIDELINES FOR CHOICE OF
ANTI-EPILEPTIC DRUGS  :
A. FOR FOCAL ONSET AND / SECONDARY GTCS:
- IST LINE DRUG : LAMOTRIGINE
- 2ND LINE DRUGS : CBZ, LEVETIRACETAM, VALPROIC ACID, TOPIRAMATE ,
ZONISAMIDE, LACOSAMIDE
- 3RD LINE DRUGS: CLOBAZAM, GABAPENTIN, OXCARBAZEPINE,
BARBITURATES , PHENYTOIN, PREGABALIN, PRIMIDONE, TIAGABINE…..
B. FOR GTCS:
- 1ST LINE DRUGS : VALPROIC ACID, LEVETIRACETAM
- 2ND LINE DRUGS : LAMOTRIGINE, TOPIRAMATE, ZONISAMIDE
- 3RD LINE DRUGS : CBZ, PHENYTOIN, PRIMIDONE, BARBITURATES……………

C. FOR ABSENCE SEIZURES :
- 1ST LINE DRUG : ETHOSUXIMIDE
- 2ND LINE DRUGS : SODIUM VALPROATE
- 3RD LINE DRUGS : LAMOTRIGINE, CLONAZEPAM……………
D. FOR MYOCLONIC SEIZURES:
- 1ST LINE DRUG: SODIUM VALPROATE
- 2ND LINE DRUGS : LEVETIRACETAM, CLONAZEPAM
- 3RD LINE DRUGS : LAMOTRIGINE, PHENOBARBITAL………………………

 5. NON-
PHARMACOTHERAPY/PATIENT-
COUNSELLING TIPS +HOME
REMEDIES FOR EPILEPSY  :1. AVOID ACTIVITIES, WHERE PATIENTS MAY PLACE
THEMSELVES/ OTHERS AT RISK, IF THEY HAVE A
SEIZURE (APPLIES AT WORK, HOME/ AT LEISURE)
2. TAKE ONLY SHALLOW BATHS/ SHOWERS
3. AVOID PROLONGED CYCLE JOURNEYS ,UNLESS
REASONABLE FREEDOM FROM SEIZURES HAS BEEN
ACHIEVED
4. ACTIVITIES, THAT REQUIRE PROLONGED PROXIMITY TO
WATER (FISHING SWIMMINING,BOATING ) SHOULD BE

5. RECONGIZED MORTALITY OF EPILEPSY SHOULD BE
DISCUSSED AT THE TIME OF DIAGNOSIS, AIMED AT
MOTIVATING THE PATIENT, TO ADAPT TO HABITS AND
LIFESTYLE, TO OPTIMIZE EPILEPSY CONTROL
6. COCONUT OIL:
- Highly effective
- Fatty acids (medium chain triglycerides) in oil  possess therapeutic effects on brain cells
- Oil  supplies energy for brain cells  relieves epilepsy symptoms
- Use 1-3 tsp of EXTRA VIRGIN COCONUT OIL (3 times a day)
7. EPSOM SALT:
- EPSOM SALT  Contains magnesium sulphate  changes psychochemical cell
relationships in the brain  reduces frequency of seizures and convulsions
- Use in the form of:
a. Epsom salt bath (2-3 times/ week)
b. Add half tsp of salt to orange juice / water  drink every morning

8. LIME:
- Popular Ayurvedic remedy
- Lime  helps improve blood circulation to brain
- Also normalizes excess calcium that may hamper brain functionality
a. (2 tsp. lime juice + half tsp. baking soda + water)  drink daily before going to bed
b. Apply lime juice on head  massage thoroughly for a few mins.  do daily before taking a
shower
9. GARLIC:
- Garlic  possesses ANTIOXIDANT, ANTISPASMODIC & ANTI-INFLAMMATORY
PROPERTIES  Promotes proper functioning of nervous, along with destruction of harmful free
radicals in body  prevents seizures and related symptoms
- Use it in the form of:
a. Mix half cup of milk + half cup water  boil  add 4-5 crushed garlic cloves  strain and drink it
once daily
b. Garlic supplements (under doctor advice)

10. PASSIONFLOWER :
- Herb  contains CHRYSIN  increases GABA amount in brain  decreases seizures frequency,
anxiety
- Use it in the form of :
a. CAPSULE, TABLET FORMS
b. HERBAL TEA (1-2 CUPS)
- Avoid in pregnancy/ lactation
11. WINTER MELON:
- Also known as ‘ASH GOURD’
- Popular Ayurvedic remedy
- Vegetable  helps keeps nervous system healthy
- Also ensures smooth functioning of brain cells
a. Half glass winter melon juice + little sugar  drink in the morning on empty stomach
b. Extract juice of crushed winter melon  add 1-2 tsp licorice powder to it  mix well  drink this
solution once daily

12. EXERCISE :
- Improves fitness, energy and mood  reduces seizures and impact of epilepsy on one’s life
- Exercise  releases positive feeling hormones into brain  increases oxygen flow to brain
- Go for warm up/ stretching exercises
- Walk for 45 mins. , 4 times a week
- Drink water before and after exercise to prevent dehydration
- Stop and rest if you are feeling tired
13. YOGA:
- Alleviates stress
- Induces relaxation
- Combination of DEEP BREATHING, PHYSICAL POSTURES AND MEDITATION 
Controls seizures and reduces other epilepsy symptoms
- Best yoga poses for epilepsy are:
a. Balasana(child’s pose) b. Nadi shodhana(alternate nostril breathing)
c. Kapotasana (pigeon pose) d. Sirsasana (headstand)

14. VITAMINS:
- Certain vitamins  control neurons that cause seizures and anxiety disorders
- Consume the following Vitamin supplements after doctor consultation:
a. Vitamin E b. Vitamin B6 c. Vitamin B1 d. Vitamin D e. Vitamin B12
15. ACCUPUNCTURE:
- “Phenomenon of applying pressure to specific points on the body, by using fine needles”
- Acupuncture  restores flow of energy throughout the body  alters brain activity  reduces
seizures
16. COUNSELLING TIPS IN PREGNANCY:
- Start FOLIC ACID 5 mg daily for 2 months before conception , to reduce risk of AED induced fetal
abnormalities
- Since some AEDs are associated with hemorrhage risk, give oral Vitamin K 20 mg daily to mother
during last month of pregnancy, and Vitamin K (1 mg i.m ) to infant at birth
17. GET ENOUGH SLEEP, AS SLEEP DEPRIVATION
TRIGGERS SEIZURES
18. MANAGE STRESS AND AVOID STRESSFUL SITUATIONS

19. IF YOU HAVE SEIZURES REGULARLY, WEAR A
‘MEDICAL ALERT BRACELET’  THIS WILLHELP PEOPLE
TO KNOW ABOUT YOUR CONDITION
20. DRINK HALF GLASS OF GRAPE JUICE DAILY
21. LIMIT ALCOHOL INTAKE
22. AVOID SMOKING
23. LOW CALCIUM AND MAGNESIUM  TRIGGERS
SEIZURES  CONSUME FOODS RICH IN THEM
24. AVOID ALL ‘WHITE PRODUCTS’ LIKE:
a. White sugar
b. White flour
c. Table salt
d. White rice

25. DO NOT SKIP MEALS, ESPECIALLY BREAKFAST
26. DO NOT CONSUME ARTIFICIAL SWEETENERS/
ADDITIVES
27. TAKE MEDICINES PRESCRIBED BY DOCTOR IN
CORRECT DOSAGES IN A TIMELY MANNER
28. DO NOT SKIP TAKING YOUR MEDICINES WITHOUT
DOCTOR’S APPROVAL
29. AVOID USAGE OF GINGKO BILOBA AND ST.JOHN’S
WORT FOR EPILEPSY ,UNLESS UNDER DOCTOR’S ADVICE
(SINCE THEY CAN INTERACT WITH AEDs)
30. FOLLOW A KETOGENIC DIET, COMPRISING:
a. High fat(nuts, cream, butter)
b. Low carbohydrate (starchy fruits, bread, pasta, grains,
sugar)

 BIBLIOGRAPHY/ REFERENCE  :
1. DAVENPORT.J.R; LEACH.P.J; ‘NEUROLOGICAL DISEASE:EPILEPSY’;DAVIDSON’S
PRINCIPLES AND PRACTICE OF MEDICINE; 22ND EDITION; Pg:1178-85
2. Tripathi.K.D; “Essentials of medical pharmacology”; 7th edition; Jaypee Publishers; “Anti-
epileptic drugs’; Pg:411-424
3. Dhillon.S; Sander.W.J; “Clinical pharmacy and therapeutics”; by Roger Walker; 5th edition;
“Epilepsy”; Pg: 489
4. Wells.G.Barbera;”Epilepsy”; Pharmacotherapy Handbook; by Joseph.T.Dipiro; Pg: 577
5. www.healthline.com
6. www.drugbank.com
7. www.webmd.com
8. http://www.thelancet.com/journals/abstract/’Top 10 home remedies To deal with Epilepsy’
9. Razzhaghi.A; “Seizure disorders”; “Comprehensive Pharmacy Review for NAPLEX by LEON
SHARGEL”; 8TH EDITION; Pg:743
10. Mc.Namara.C.J; “Pharmacotherapy of the Epilepsies”; Goodman & Gilman’s Pharmacological
basis of Therapeutics; 11th edition; Pg: 501

THANK YOU!!!   
@rxvichu-alwz4uh!!

Epilepsy and seizures a deep insight- by Rxvichu!!

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