This interesting ppt deals with the Pharmacology of Antiepileptic drugs and the treatment of different types of seizures with beautiful illustrations....

2. DO YOU KNOW…

4. Interesting Facts about Human Brain
∗ The human brain has about 100,000,000,000
(100 billion) neurons
∗ There are about 100,000 miles of blood
vessels in the brain.

5.  The human brain is the fattest organ in the body
and may consists of at least 60% fat.
 There are no pain receptors in the brain, so the brain
can feel no pain.
 Neurons multiply at a rate 250,000 neurons/minute
during early pregnancy

14. Dr. V.Sathyanarayanan M.D
Professor of pharmacology

15.  Group of disorders of CNS
 Affects 5-10/ 1000 population
 2nd
most common CNS disorder after stroke
 Known as disease of lightening

19.  Characterized by paroxysmal cerebral
dysrhythmia
 Manifests as brief episodes of loss or
disturbance of consciousness
 with or without convulsions, sensory or
psychiatric phenomena

25. Stabilize membrane and prevent
depolarization by action on ion
channels
Increase GABAminergic transmission
Decrease EAA transmission

27. GABA-A Receptor
Binding Sites
Cl-

30. Action on Ion
Channels
Enhance GABA
Transmission
Inhibit EAA
Transmission
Na+
:
Phenytoin, Carbamazepine,
Lamotrigine, Topiramate
Valproic acid
Ca++
:
Ethosuximide
Valproic acid
Benzodiazepines
(diazepam, clonazepam)
Barbiturates (phenobarbital)
Valproic acid
Gabapentin
Vigabatrin
Topiramate
Felbamate
Felbamate
Topiramate
Na+
: For general tonic-
clonic and partial seizures
Ca++
:
For Absence seizures
Most effective in myoclonic but
also in tonic-clonic and partial
Clonazepam: for Absence

31. Classical
 Phenytoin
 Phenobarbital
 Primidone
 Carbamazepine
 Ethosuximide
 Valproic Acid
 Trimethadione
Newer
 Lamotrigine
 Felbamate
 Topiramate
 Gabapentin
 Tiagabine
 Vigabatrin
 Oxycarbazepine
 Levetiracetam
 Fosphenytoin
 Others

33.  Act by Enhancing GABA A receptor mediated
synaptic inhibition
 Increases seizure threshold, limits spread
 Cause sedation, decrease intelligence, learning,
memory
 Cheapest antiepileptic
 Effective in GTCS, SPS, CPS
 Less popular

37.  A prodrug
 Produce active metabolites
 Efficacy similar to phenobarbitone
 Useful in refractory epilepsy adjuvant to
phenytoin

39.  Barbiturate analogue
 M.O.A  prolong the inactivated state of
neuronal voltage dependent Na+ channels,
stabilize neuronal membrane
 80-90% protein bound
 Metabolism changes from 1st
order to zero
order
 Monitoring is very helpful in tailoring dosage

45.  Gum hypertrophy – 20%
 Hirsutism, coarsening of face, acne
 Hypersensitivity reactions
 Megaloblastic anemia, Osteomalacia,
hyperglycemia
 Fetal hydantoin syndrome

57.  High plasma levels  cerebello vestibular
syndrome – ataxia, vertigo, nystagmus
 Drowsiness
 mental confusion
 hallucinations
 Epigastric pain
 I.V injection cause local vascular injury, fall in
BP

66.  Induce microsomal enzymes  Oral
Contraceptive Pills failure
 Displacement reactions  Valproate
displaces phenytoin  increases
plasma level
 Carbamazepine induce metabolism

68. 1st
line antiepileptic for
 Generalized tonic-clonic convulsions
 Simple partial seizures
 Complex partial seizures
 DOSE : 100 mg BD
 Trigeminal neuralgia -2nd
choice
 Digitalis induced arrhythmias

75.  A Prodrug of phenytoin
 Given i.v. or i.m.
 rapidly converted to phenytoin
 Given i.v  Avoids complications
associated with phenytoin: vein irritation,
tissue damage
 Can be injected in drip
 Alternative to phenytoin in status
epilepticus

80.  Chemically related to imipramine
 MOA – Similar to phenytoin
 75% protein bound
 Long half life
 Autoinduction occur

82.  Hypersensitivity
 Dose related neurotoxicity- drowsiness,
ataxia, vertigo
 Hypersensitivity reactions- Hepatitis, lupus
like syndrome
 Enhance ADH action
 Aplastic anemia
 Minor fetal malformations

91. Induce microsomal enzymes – OCP
failure
Metabolism Induced by phenytoin &
valproate
Metabolism Inhibited by erythromycin

93. 1ST
choice in GTCS,CPS,SPS
1st
choice in Trigeminal neuralgia ,
post herpetic neuralgia
and other neuropathic pain
Manic depression
Acute mania
Dose : 200-400 mg TDS

101. Less toxic than carbamazepine
Mild enzyme inducer – less drug
interactions
Less side effects
Cause hyponatremia

110. Broad spectrum anticonvulsant
MOA – prolongation of Na channel
inactivation
Attenuation of Ca ++ mediated T current
Inhibit GABA transaminase  increase
GABA
Increase GABA synthesis
PK- 90% protein bound

112.  Drowsiness, ataxia, tremor –dose related
 Alopecia, curling of hair, weight gain
 Hypersensitivity
 Fulminant hepatitis in children – rare but
serious
 Young girls – menstrual irregularities,
polycystic ovarian disease
 Monitor liver function
 Neural tube defects in pregnancy

121.  Displace phenytoin from
protein binding sites
 Induce metabolism of
carbamazepine
 Contraindicated with
carbamazepine,
clonazepam

122. Drug of choice for Absence seizures
Alternative/ adjuvant drug for GTCS,
SPS, CPS
1st
choice for myoclonic seizures, atonic
seizures
Prophylaxis in migraine
Mania
Bipolar depression

130. Coordination compound of
valproic acid with sodium
valproate ( 1 : 1 )
Better gastric tolerance
Better bioavailability

133. Not used for long term therapy
because of
Prominent sedative action
Rapid development of tolerance

136. Drug of choice for
status epilepticus
 tetanus
Eclampsia
Convulsant poisoning
Rectally given for febrile
convulsions in children

141. Given i.v – can cause
marked fall in BP,
Respiratory depression
Cause sedation , tolerance

144.  Benzodiazepine with prominent
anticonvulsant activity
 Potentiate GABA induced Cl influx
 ADR- sedation, lack of concentration,
irritability, ataxia
 Uses – absence seizures, adjuvant in
myoclonic, akinetic seizures, infantile spasms
 Limitation – tolerance in 6 months

151.  Similar to clonazepam
 Used as an adjuvant to other antiepileptic
drugs in Refractory epilepsy
 ADR – sedation, psychomotor retardation

154.  Alternative to diazepam in status epilepticus
 And emergency control of other convulsions
 Action is more sustained than diazepam

156.  Like carbamazepine Blocks Na channels 
stabilizes presynaptic membrane
 blocks high voltage dependent Ca channels
 Prevents release of excitatory
neurotransmitters
 Broad spectrum action
 Used as monotherapy and add on drug

158.  Sedation,
 ataxia,
 diplopia,
 RASH –sometimes life threatening
 Negative effect on cognitive function not
reported

163.  GABA derivative
 Increases GABA release
 Add on drug in SPS, CPS
 Pain due to diabetic neuropathy, post herpetic
neuralgia
 Migraine
 Manic depression
 ADR- sedation, tiredness

170.  Inhibit GABA transaminase  increases
synaptic GABA
 ADR – can cause behavioral changes –
(drawback),
 drowsiness, amnesia,
 TUNNEL VISION
 Adjuvant medication for refractory epilepsy

174.  Broad spectrum anticonvulsant
 Has Risk of aplastic anemia, hepatic failure
 Reserved for use in refractory epilepsies

177.  Recent drug
 Prevents GABA uptake  Potentiates GABA
mediated synaptic inhibition
 ADR – sedation, tiredness
 Add on drug for partial seizures

179.  Weak Carbonic anhydrase inhibitor
 Broad spectrum anticonvulsant
 Act by antagonizing glutamate,
 GABA potentiation, prolonging Na channel
prolongation
 Useful as supplementation in refractory SPS,
CPS, GTCS
 Approved for prophylaxis of migraine
 ADR – sedation, ataxia, psychiatric
symptoms

183.  Adjuvant drug in refractory partial seizures
 Mechanism unknown
 ADR- tiredness, drowsiness

186.  Sulfonamide derivative
 Has broad spectrum action
 Has Long half life
 May cause kidney stones, oligohydrosis

191.  Genetic Epilepsies:
Mutation causes increased excitability
or
brain abnormality

192. Acquired epilepsy
 Physical insult to the brain
 50% of patients with severe head injuries will develop a seizure
disorder
 Brain tumors,
 stroke,
 CNS infections,
 febrile seizures
 Initial seizures cause anatomical events that lead to future
vulnerability
 Latent period occurs

197.  A drug which decreases the frequency and/or
 severity of seizures in people with epilepsy
 Treats the symptom of seizures, not the
underlying epileptic condition

199.  Goal—maximize quality of life by
minimizing seizures and adverse drug
effects
 Currently no “anti-epileptogenic” drugs
available

201.  Seizure type
 Epilepsy syndrome
 Pharmacokinetic profile
 Interactions/other medical conditions
 Efficacy
 Expected adverse effects
 Cost

217.  Don’t stop drugs
 cautiously decrease the dose
 carbamazepine , lamotrigene are safer
 Add folic acid, vitaminK

223.  Medical emergency
 Continuous epilepsy without intermission >
30min
 Diazepam 10 mg i.v bolus 2mg/ minute or
clonazepam or (Now - LORAZEPAM 4mg i.v
preferred)
 Phenobarbitone or phenytoin act slowly
 Fosphenytoin i.v

224.  I.V midazolam/ propofol/ thiopentone
 with or without muscle relaxants with
positive pressure ventilation

226.  Airway
 Oxygen
 Fluid & electrolytes
 BP
 Cardiac rhythm
 Glucose
 Care of the unconscious

230.  Focal with minimal spread of abnormal
discharge
 Patient often exhibits abnormal activity of
single limb
 normal consciousness and awareness are
maintained

232.  Carbamazepine, phenytoin  1st
line
 Valproate  second line, hepatotoxic
 Young girls  carbamazepine
 Lamotrigene, gabapentin, topiramate –
good alternatives
 Newer drugs – as add-on therapy
 Post head injury – phenytoin, valproate

234.  Local onset, then spreads
 Impaired consciousness
 Clinical manifestations vary with site of origin and degree
of spread
 Presence and nature of aura
 Automatisms
 Other motor activity
 Temporal Lobe Epilepsy most common

236.  Difficult to control
 Relapses common
 Drug of choice – carbamazepine
 If not controlled – add phenytoin, valproate
 Refractory cases- lamotrigene, gabapentin,
clobazam, topiramate

238.  Sudden onset of impaired consciousness
associated with staring
 Usually Less than 30 seconds
 Ethosuximide
 Valproate – more commonly used , superior
in mixed absense and GTCS
 LAMOTRIGENE good alternative
 Clonazepam 2nd
line
 clobazam

241.  Sudden, brief, shock like contraction of
muscles
 Valproate
 lamotrigene

242.  Sudden loss of postural tone and the head
may drop or the person may drop
 Valproate
 lamotrigene

244.  Some children especially under 5 Develop
convulsions during fever
 Don’t allow temperature to rise
 External cooling
 Paracetamol
 Treatment - Rectal diazepam 0.5 mg/kg
 i.v preparation can be used
 Prophylaxis with rectal or oral diazepam at
the onset of fever

248.  Corticosteroids
 Valproate, clonazepam as adjuvants

250.  K+ channels have important inhibitory control
over neuronal firing in CNS
 K+ channel agonists would decrease hyper
excitability in brain
 valproate
 Retiagabine is a novel AED in clinical trials

253.  A mechanic was removing a cylinder head
from the motor of a motorcycle when he
spotted a well-known heart surgeon in his
shop.
 The mechanic shouted across the garage,
"Hey, Doc, can I ask you a question?“

254.  The surgeon a bit surprised, walked over to the
mechanic .
 The mechanic asked, "So Doc, look at this engine. I
open its heart, take valves out, fix 'em, put 'em back
in, and when I finish, it works just like new.
 So how come I get such a small salary and you get
the really big bucks, when you and I are doing
basically the same work?“

256. The surgeon paused, smiled
and leaned over,
 and whispered to the mechanic...
"Try doing it with the engine running."