FATHIMA MPharm CONTENTS DEFINITION EPIDEMIOLOGY AETIOLOGY PATHOPHYSIOLOGY TYPES OF SEIZURES GENERAL MECHANISM OF ACTION DRUGS EPILEPSY A chronic disorder characterized by recurrent seizure ID: 734691
Download Presentation The PPT/PDF document "ANTI EPILEPTIC DRUGS AFSAR" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
ANTI EPILEPTIC DRUGS
AFSAR
FATHIMA
M.PharmSlide2
CONTENTS
DEFINITION
EPIDEMIOLOGY
AETIOLOGY
PATHOPHYSIOLOGY
TYPES OF SEIZURES
GENERAL MECHANISM OF ACTION
DRUGSSlide3
EPILEPSY
:
A chronic disorder characterized by
recurrent seizure
SEIZURE
:
Is a violent involuntary spasmodic
contraction of skeletal muscle
EPIDEMIOLOGY
:
1% worlds
population
& 57/1000Slide4
AETIOLOGY
in children-idiopathic
in young- hypoxia, birth asphyxia, intracranial trauma during birth, metabolic disturbances, infection
In adult- head injury, alcohol abuse, cerebrovascular disease
DIAGNOSIS
:
EEG( electroencephalo gram)
MRI(magnetic resonance imaging)
CT scan
brain mapping
Slide5Slide6
SEIZURE CLASSIFICATION
PARTIAL
ONE PART OF BRAIN
GENERALISED
ENTIRE BRAIN
SIMPLE
COMPLEX
ABSENCE
TONIC CLONIC
FEBRILE
SEIZURE
STATUS
EPILEPTIC-US
MYOCLONICSlide7
MECHANISM
OF
ANCTIONS
a
) enhancement of GABAnergic transmission
b
) diminution of excitatory transmission
c
) modification of ionic conductanceSlide8Slide9Slide10
SEIZURE TYPE
1ST LINE TREATMENT
2
ND
LINE TREATMENT
PARTIAL SEIZURE
SIMPLE PARTIAL SEIZURE
CARBAMAZEPINE
VIGABATRIN
,
ZONISAMIDE
COMPLEX PARTIAL SEIZURE
PHENYTOIN
CLOBAZAM
GENERALISEDSEIZURES
TONIC CLONIC
VALPROATEVIGABATRINTONICCARBAMAZEPINECLOBAZAMCLONICPHENYTOIN, LAMOTRIGINEPHENOBARBITAL
ABSENCEETHOSUXIMIDE ,VALPROATECLONAZEPAM, LAMOTRIGINEACETAZOLAMIDEATONICCLONAZEPAM ,CLOBAZEPAMLAMOTRIGINE ,CARBAMAZEPINEPHENYTOIN ,ACETAZOLAMIDEMYOCLONICVALPROATE, CLONAZEPAMPHENOBARBITAL,
ACETAZOLAMIDETOPIRAMATESlide11
Cyclic
ureides: Phenytoin,
fosphenytoin
MECHANISM
OF
ACTION
Blocks high-frequency firing
of
neurons through
action
on voltage-gated
(
VG) Na+channels, decreases synaptic release
of
glutamate
PHARMACO KINETICS
Absorption is formulation dependent,highly
bound to plasma proteinsno active metabolites ,Dose dependent elimination, ,t1/2 12-36h fosphenytoin is for IV, IM routesToxicity
: Diplopia, ataxia
,,
hirsutism, neuropathy
Interactions:
isoniazid, felbamate, oxcarbazepine, topiramate, fluoxetine, fluconazole, digoxin, quinidine
, cyclosporine, steroids, oral contraceptives,.Slide12
Phenobarbital
M
echanism of action
:
Enhances
phasic GABAa receptor responses ,Reduces excitatory synaptic responses
P
harmaco kinetics
:
Nearly complete
absorption, not significantly
bound to
plasma Proteins,peak
concentrations in
4
h, no active metabolites,
t1/2 varies from 75 to 125hToxicity: Sedation, cognitive issues, ataxia, hyperactivity Interactions:Valproate,carbamazepine,felbamate,phenytoin,cyclosporine
, felodipine,,nifedipine
, nimodipine, steroids,theophylline
, verapamil, Slide13
Ethosuximide
M
echanism of action
:
Reduces
low
threshold Ca2
+ currents (Ttype
)
P
harmacokinetics:
Well
absorbed orally,
with peak levels
in 3-7 h, not protein-bound completely metabolized to inactive compounds ,t1/2 typically 40 hToxicity
: Nausea, headache,
dizziness,
hyperactivity
Interactions
: Valproate,phenobarbital, phenytoin, carbamazepine,rifampicinSlide14
Tricyclics
:
Carbamazepine
M
echanism of action:
Blocks
high-
frequencyfiring
of
neurons through
action on
VG Na
+
channels decreases
synaptic release
of glutamatepharmacokinetics: Well absorbed orally, with peak levels
in 6 to 8 h no significant protein binding metabolized in part to active 10-11-epoxide t1/2 of
parent ranges from
8to 12 h in treated
patients to 36 h in normal subjects
Toxicity:
Nausea,, headacheInteractions:
valproate, fluoxetine, verapamil, macrolide antibiotics, isoniazid.Slide15
Benzodiazepines :
Diazepam
&LORAZEPAM
MECHANISM OF
ACTION
:
Potentiates
GABAA responses
PHARMACO KINETICS:
Well absorbed
orally
rectal administration
gives
peakconcentration
in ~1 h with
90% bioavailability
IV for status epilepticus
,highly protein-boundextensively metabolized to several active metabolites, t1/2 ~2 dToxicity: SedationSlide16
Clonazepam
MECHANISM OF
ACTION:
As
for diazepam
PHARMACO KINETICS
:
>80
% bioavailability
Extensively metabolized
but no
active metabolites
t1/2 20-50 h
Toxicity
: Similar to
diazepamSlide17
GABA
derivatives :
Gabapentin
MECHANISM OF
ACTION:
Decreases
excitatory transmission
by
acting on
VG Ca2+
channels presynaptically
PHARMACO KINETICS:
Bioavailability 50%, decreasing
with increasing
doses ,
not bound to plasma proteins
not metabolized,t1/2 6-8 hToxicity: Somnolence, dizziness, ataxiaSlide18
Pregabalin
MECHANISM OF
ACTION:
As
for
gabapentin
PHARMACO KINETICS:
Well absorbed orally ,
not
bound
to plasma proteins
not
metabolized,
t1/2 6-7 h
Toxicity: Somnolence, dizziness,
ataxiaSlide19
Vigabatrin
MECHANISM OF ACTION
:
Irreversibly inhibits GABA-trans aminase
PHARMACO KINETICS:
70% bioavailable ,
not
bound
to plasma
proteins
not metabolized,
t1/2 5-7
h
Toxicity
: Drowsiness, dizziness,
psychosis visual
field lossSlide20
Miscellaneous:
Valproate
MECHANISM OF
ACTION
:
Blocks
high-frequency firing
of
neurons, modifies
amino
acid metabolism
PHARMACO KINETICS
:
Well absorbed from
several formulations
highly bound to plasma proteinsExtensively
metabolized, t1/2 9-16 hToxicity: Nausea, tremor, weight gain, hair loss, teratogenic, hepatotoxic Interactions: felbamate, rifampin, ethosuximide, primidoneSlide21
Lamotrigine
MECHANISM OF
ACTION
:
Prolongs
inactivation of
VG-Na+
channels,acts presynaptically on
VG-Ca2+
channels,decreasing glutamate release
PHARMACO KINETICS
:
Well absorbed
orally
no
significant protein binding extensively metabolized, but no active metabolites t1/2 25-35 hToxicity: Dizziness, headache, diplopia, rashInteractions
: Valproate,
oxcarbazepine,
primidone, succinimides,
topiramateSlide22
Levetiracetam
MECHANISM OF
ACTION
:
Action
on
synaptic protein SV2A
PHARMACO KINETICS
:
Well absorbed orally
not
bound
to plasma proteins
metabolized to
3 inactive metabolites
t1/2 6-11 hToxicity: Nervousness, dizziness, depression, Interactions
:,primidoneSlide23
Tiagabine
MECHANISM OF
ACTION:
Blocks
GABA
reuptake in
forebrain
by selective
blockade
of GAT-1
PHARMACO KINETICS:
Well absorbed
highly
bound
to plasma proteins
extensively metabolized
, but no active metabolites t1/2 4-8 h
Toxicity: Nervousness, dizziness, depression, seizures Interactions: Phenobarbital, phenytoin, carbamazepine, primidoneSlide24
Topiramate
MECHANISM OF
ACTION
:
Multiple
actions
onsynaptic function, probably
via
actions on phosphorylation
PHARMACO KINETICS
:
Well
absorbed,
not bound to
plasma proteins
extensively metabolized, but 40% excreted unchanged in
the urine no active metabolites t1/2 20 h, but decreases with concomitant drugsToxicity
: confusion
Interactions
:
Phenytoin, carbamazepine,
oral contraceptives,, lithiumSlide25
Zonisamide
MECHANISM OF
ACTION
:
Blocks
high-frequency firing
via action on
VG Na+ channels
PHARMACO KINETICS
:
Approximately
70%
bioavailable orally
minimally
bound to
plasma proteins >50%
metabolized, t1/2 50-70 hToxicity: Drowsiness,, confusion.Slide26
Lacosamide
MECHANISM OF ACTION
:
Enhances slow inactivation
of
Na+ channels
Blocks effect
of
neurotrophins (via
CRMP-2
)
PHARMACO KINETICS
:
Well absorbed ,
minimal protein binding
one major nonactive metabolite ,t1/2 12-14 h
Toxicity: Dizziness, headache, nausea small increase in PR intervalSlide27
RETIGABINE
MECHANISM OF
ACTION
:
Enhances
k+ channel opening
PHARMACOKINETICS
:
Readily
absorbed,Requires 3-times daily dosing
TOXICITY
:
dizziness, confusion, blurred visionSlide28
RUFINAMIDE
MECHANISM OF
ACTION
:
Prolongs
inactivation of VG Na+ channels
PHARMACOKINETICS
:
Well absorbed orally,Peak concentration in 4-6h
t1/2 6-10h,Minimal plasma protein binding
No active metabolites ,Excreted in urine
TOXICITY
:
vomiting ,diarrhea
INTERACTIONS
: not metabolized by CYP 450 EnzymesSlide29
REFERENCES
Basic and clinical pharmacology- katzung, RogerJ.Porter,MD ,& Brain S. Meldrum,MB, PhD 11
th
edition
RANG & DALE’S Pharmacology 7
th
edition
CLINICAL PHARMACOLOGY BY Rooger & Walker
Conceptual pharmacology by D.
jagadeesh Prasad
Goodman & GilmanSlide30