3. Seizure: Is a paroxysmal event due to
abnormal , excessive and hypersynchronous
discharges from an aggregate of central nervous
system neurons.
Epilepsy : It is clinical phenomenon in which a
person has recurrent seizures due to a chronic
underlying process.
4. GENERALISED SEIZURES
- involve cerebral hemisphere diffusely
• GTCS-main seizure type , 10% of all persons with
epilepsy,lasts 1-2 min.
• Usual seq.-auracryunconsciousnesstonic spasm of
body
• ABSENCE SEIZURES-prevalent in children, last 1-2 min.
• Momentary loss of consciousness,no muscular
component,EEG spike and wave pattern of 3 cycles per sec.
• ATONIC SEIZURE-unconsciousness with relaxation of all
muscles due to excessive inhibitory discharges
• MYOCLONIC SEIZUREshock like momentary
contracture of group of muscle
5. PARTIAL SEIZURE
Discrete region of cerebral cortex is involved
SIMPLE PARTIAL usually lasts 1-2 min
Confined to group of muscles depending upon area
of cortex involved.
COMPLEX PARTIAL SEIZUREunconscious
with aura purposeless movements,emotional
changes lasting 1-2 min
11. Mechanism of Action
Anti epileptic drugs act primarily by
blocking the initiation or spread of
seizure.
Decrease propagation of action potentials
ß Na+, Ca++ influx (delay depolarization
/ prolong repolarization)
Ý Cl- influx (hyperpolarize
membrane)
ß glutamate release
12. Exert antiepileptic effect without CNS
depression
Mechanism of action
Therapeutic dose – prolonged inactivation of
voltage sensitive sodium channels
Higher concentration –
Reduction in calcium influx
Facilitate GABA
Inhibit Glutamate – decrease intracellular sodium
ion
13. Absorption is slow per orally
High plasma protein binding(90%)[widely
distributed]
Metabolised in liver by CYP2C9,2C19
First → 0 order kinetic(high dose)
t half 12-24 hrs at therapeutic level
14. Gum hypertrophy
Hirsutism, acne, coarsening of facial features
Megaloblastic anaemia
Osteomalacia
Fetal hydantoin syndrome
At higher concentration:
Ataxia, vertigo, nystagmus
Alteration in behavior, mental confusion & hallucination
Epigastric pain, nausea & vomiting
Mod elevation of hepatic transaminases
Hyperglycemia and glycosuria
15. Phenytoin -↓ OCP, theophylline
Phenytoin inhibits warfarin metabolism
Phenobarbitone competitively inhibits phenytoin metabolism, by
enzyme induction both enhances each others degradation.
Carbamazepine & phenytoin ↑ metabolism of each other
Indications
GTCS
Simple partial seizures
Complex partial seizures
Status epilepticus
Dose : 100 mg BD
16. Ist efficacious antiseizure
Mechanism of action
Enhancement of GABAA receptor mediated
synaptic inhibition
Pharmacokinetics
Slow oral absorption
40-60% plasma protein bound
25% renal excretion
17. Sedation (most frequent)
Nystagmus,ataxia(excessive dosage)
Irratability,confusion in children
Megaloblastic anemia
osteomalacia
Uses
GTCS
Partial seizures
Status epilepticus
Dose: 60 mg 1-3 times a day
18. Chemically related to imipramine
Mechanism of action
Like phenytoin –slow rate of recovery of Na channels from
inactivation at therapeutic conc.
PHARMACOKINETICS
Absorption is slow and variable
Metabolized in liver to 10 -11 epoxycarbamazepine(active form)
Initial t½ (20 – 40 hours)
Later (10 – 20 hours)
Therapeutic conc. 6-12μg/dl
19. Sedation, dizziness, vertigo and ataxia,blurred vision,
GIT upset
Rashes, photodermatitis, hepatitis
Water retention and hyponatremia – old age
Aplastic anaemia,eosinophilia,lymphadenopathy
Drug interaction
Phenytoin, valproate and phenobarbitone - ↓carbamazepine
conc.by CYP3A4 induction
Fluoxetine and isoniazid and eryhromycin -↑ carbamazepine
Carbamazepine lowers
valproate,lamotrigine,tiagabine,topiramate
20. Effective in GTCS and SPS
Trigeminal and other neuralgias
MDP and acute mania
Dose : 200-400 mg TDS
Children- 15-30 mg /kg /d
21. 10 mono hydroxy derivative of carbamazepine
Advantage –weak enzyme induction
Conc of VALPROATE ,PHENYTOIN not decreased
USES
In partial seizures
22. Primary agent for absence seizure
MECHANISM OF ACTION
Selectively suppressed T type Ca currents without
effecting other types of calcium and sodium currents
PHARMACOKINETICS
Absorption complete(slow),peak plasma-3hrs
Half life-40-50hrs
Metabolism – liver, Excretion – kidney
24. Broad spectrum anti seizure drug
MECHANISM OF ACTION
- Prolongation of sodium channel inactivation
- Suppression of calcium mediated T currents
- Increase in GABA release by inhibiting GABA
transaminases
PHARMACOKINETICS
well absorbed orally, high plasma protein bindings
Metabolism – liver ,
Excretion – kidney
26. Drug of choice
Absence seizure
Myoclonic and atonic seizure
Alternate Drugs
mania, GTCS, SPS and CPS
Dose:
Start with 200 mg TDS max dose 800 mg TDS
Children- 15-30 mg/kg/d
27. Benzodiazepines potentiate GABA induced Cl
influx .
Not used for long term due to prominent sedation
and rapid development of tolerance.
It is first line drug for:
Emergency control of convulsions
Status epilepticus
Tetanus
Eclampsia
Dose : 0.2-0.5 mg/kg slow iv injection followed by small
repeated doses max 100 mg /d
ADR: Thrombophlebitis of injected vein, marked fall in BP,
respiratory depression
28. Action like carbamazepine
Broad spectrum
Mechanism of action
- Prolongation of sodium channel inactivation
- May directly block sodium channels – stabilized
presynaptic membrane and prevent glutamate and
aspartate release
- Indications:
- Add on therapy in refractory cases of GTCS and partial
seizures
- Dose: 50mg/d initially , increase upto 300 mg/d
29. Absorbed well and metabolized in liver
Drug Interaction
- Phenytoin carbamazepine or phenobarbitone
decrease t½
- Valproate increase plasma level
- Lamotrigine decreases valproate plasma level
ADR
Sleepiness, dizziness, ataxia, diplopia and
vomiting ,Rash – severe reaction
-
30. MECHANISM OF ACTION
enhances GABA release
PHARMACOKINETICS
Absorption well, excretion unchanged in urine
ADR
Sedation, dizziness, unsteadiness
INDICATION
Simple partial seizure
Refractory partial seizures
Complex partial seizure
Dose: 300 mg OD , increase up to 300- 600 mg TDS as
required
31. MECHANISM OF ACTION
inhibit gaba transporter GAT-1reduces gaba
uptake in neurons
Pharmacokinetics
Rapid oral absorption
Extremely plasma protein bound
Liver metabolism by CYP3A
indication
Add on therapy of partial seizures
ADR
Sedation, abdominal pain
32. Mechanism of action
- Prolongation of sodium channel inactivation
- Post synaptic GABA potentiation
- Glutamate receptor antagonist
- Pharmacokinetics
- Rapid oral absoprtion
- 10-20% plasma protein binding
- Excreted in urine
Indications
- SPS, CPS and GTCS
- ADR
- Sedation, ataxia, psychiatric symptoms and renal
stones
33. Mechanism of action
Inhibit t type Ca channels
Prolong inactivation of Na channel
pharmacokinetics
Complete oral absorption
40% binding to plasma protein
85% urine excretion
35. Partial Seizure(adjunctive In >17yrs)
MECHANISM OF ACTION
Inactivation of Na channel
RUFINAMIDE
Adjunctive treatment of lennox gastaut syndrome
MECHANISM OF ACTION
Slow inactivation of Na channels
36. Refractory partial seizure
Infantile spasm
MECHANISM OF ACTION
Irreversible GABA tranaminase inhibitorincrease GABA
LEVETIRACETAM
Refractory partial seizures
Mechanism of action is not known
Free of drug interactions
Few side effects
Good tolerability , now increasingly used in CPS, GTCS
DOSE: 0.5 mg BD
37. seizure type first line drugs
second line drugs
Simple partial seizure Carbamazepine
phenytoin
valproate
Gabapentin
lacosamide
tiagabine
rufinamide
topiramate
zonisamide
Complex partial seizure carbamazepine
phenytoin
valproate
Gabapentin
lacosamide
tiagabine
rufinamide
topiramate
zonisamide
Partial with generalised tonic clonic
seizure
carbamazepine
phenytoin
valproate
phenobarbital
Gabapentin
lacosamide
tiagabine
rufinamide
topiramate
38. Seizure type First line drugs second line drugs
Absence seizure Valproate
ethosuximide
Lamotrigine
Topiramate
Myoclonic seizure Valproate
Clonazepam
Levetiracetam
Lamotrigine
Tonic clonic seizure
carbamazepine
phenytoin
valproate
phenobarbital
Lamotrigine
Topiramate