ANTI

CONVULSANTS

DRK.BOB-
DURU

Epilepsyaffectsapproximatel
y1%oft hewor l
d'spopulat
ionandhashasmanydi v
ersecauses
whi chincludesthef ullrangeofneurol
ogicaldiseases.Anti-seizur
edr ugsarealsousedt o
managef ebril
econv ul
sionsorsei
zureassoci at
edwi t
hacut ei l
lness.Thesearenotnor mal l
y
termedepi lepsyunlesstheymorphintochronicsei
zures.Iti
sal way simport
anttodiscov
ert he
under l
yi
ngcauseofsei zuresandtreatthiswhenev erapplicabl eeghy pocal
cemia.Seizure
treatmentnor mall
yisbasedupontheclassifi
cati
onoftheseizur edisorder
.

About60% ofpatient
swi llr
espondadequat
elytoanti
-sei
zuremedi
cat
ionwhil
etherestwi
l
l
exhi
bitr
esist
ancet otherapy.Thi
sdrugresi
stance mayoccuratinit
iat
ionoftr
eat
mentor
devel
oplat
er.Reasonsforthi
sphenomenonhavenotbeeneluci
dat
ed.

Seizur eswhi
charedif
fi
culttocontroli
ncludethoseassociat
edwithprogr
essi
vebraindamage
i
nchi l
drenandsomefocalseizuresinadult
s.Somesei zur
eswil
lrespondtosurgi
calresect
ion,
anot hermodeoft her
apyi sv agusnervestimulat
ionwhichwil
lhelpsomepeopl ewi thdrug
resistantsei
zur
es.

A)BASI
CPHARMACOLOGYOFANTI
-SEI
ZUREDRUGS

Manyoft he anti
-seizur
e drugs can be cl
assi
fi
ed int
of i
ve chemi
calgr
oups bar
bit
urat
es,
hy
dant
oins,oxazol
idinedi
ones,succi
nimidesandacet
ylur
eas.

PHARMACOKI
NETI
CS

Mostoft hesecompoundsar ewellabsorbedev enthoughtheyareonlysl

ight
lysolubl
ey et80-
100%oft hedosereachesthecir
culati
on.Theyar e,gener
all
y,poor
lyboundtoplasmapr otei
ns,
cl
earancei schi
eflyhepati
cwi t
hl ow extract
ionr ati
oandmanyar emet abol
izedto active
product
swhi chareclear
edbythel i
ver.Theyhav eslowplasmaclear
anceandt husaremost ly
medium tolongacti
ngagents.
B)DRUGSUSEDI
NPARTI
ALSEI
ZURESANDGENERALI
ZEDTONI
C-CLONI
CSEI
ZURES

Thepr i
mar yagentswhichhav ebeeninusear ephenytoi
n,carbamazepine,val
proat
eandt he
bar
bit
urates.Newerdr ugsarealsonowav ai
l
able.Theseincl
ude:eslicarbazepi
ne,l
amotri
gine,
l
eveti
racetam, gabapentin, oxcar
bazepi
ne, pregabal
i
n, reti
gabin, topi
ramate, vi
gabat
r i
n,
l
acosami de,andzonasimi
de.

1.PHENYTOI
N

I
tist
heol destnonsedati
veant
i-
sei
zur
edr
ug.Fospheny
toi
nisapr
odr
ugofpheny
toi
nandi
s
admi
nist
eredpar
enter
all
y.

Mechani
sm ofAct
ion

Phenyt
oinbl
ockshi
gh-
fr
equencyr
epet
it
ivef
ir
ingofact
ionpot
ent
ial
sandt
heper
sist
entNa
cur
rent
.

Cl
ini
caluses

I
tisef
fect
iveagai
nstpar
ti
alandgener
ali
zedt
oni
c-cl
oni
csei
zur
es

Phar
macoki
net
ics

GItractabsorpt
ionapproximatesahundr edpercent.Peakplasmalevelaft
eroralfor
mulat
ion
mayr angefrom 3to12hour s.Int
ramuscularabsorpt
ionaft
erinj
ect
ionisunpredi
ctabl
eandim
administ
rati
on i
s notr ecommended.Pheny toi
nis highl
ybound t o pl
asma protei
n and i
t
accumulatesinthebr
ain,li
ver
,muscleandf at.

Pheny
toi
nisconv
ert
edt
oinact
ivemet
abol
i
teswhi
char
ethenexcr
etedi
ntheur
ine.

Hal
f-
Lif
evar
iesf
rom 12t
o36hour
s

Athi
gherconcent
rat
ionst
hehal
f-
li
fei
ncr
easesmar
kedl
y.
Ther
apeut
icLev
elAndDosage

Pati
entscanbegivenaloadi
ngdose,ei
theror
all
yorintravenousl
y.I
nst
atusepi
l
ept
icusthi
sis
gi
ven ivusing f
ospheny
toi
n.With or
al.medicat
ion,thisisusuall
y300mg/dayin adul
ts.
Therapeut
icpl
asmalevel
will
be10-
20mcgi nmostpatients.

I
fseizur
econtr
olhasnotbeenachi
evedwithi
nit
ialt
reat
mentt
hent
hedosageshoul
dbe
i
ncr
easedver
ygradual
l
yot
her
wiset
oxi
coutcomesmayoccur.

Dr
ugi
nter
act
ions

Withapl asmapr oteinbindingof90%itcanbedi spl

acedbyot herhighl
ybounddr ugssuchas
sulf
onami de.Renaldi seasecausesadecreaseinpr ot
einbinding,andphenyt
oinal sohasan
affi
nit
yforthyroi
dbi ndingglobul
insucht
hatitcanconfusesomet est
softhyr
oidfunctionsuch
thatitmaybemor eaccur at
et omeasurethet hyr
oidstimulati
nghor monelevels(TSH)t o
ascertai
nthyroi
df unctioninpati
ent
swhoaret aki
ngphenytoi
n.

Toxi
cit
y

Ny stagmusandl ossofsmoot hocul arpursui

tmovementcanoccurbutwillnotrequi
redose
adjustmentunl i
kedipl
opi
aandat axia.Sedati
onwil
lnormall
yoccuronlyatv eryhi
ghdoses.
Other sincl
udegingi
valhyper
plasia,hir
suti
sm,andwithlongter
m usage,coarseni
ngoffacial
features,mi l
d peri
pher
alneur opathy and abnor
mali
ti
es inv i
tD met aboli
sm leadi
ng to
osteomal aci
a.

2.Mepheny
toi
n,Et
hot
oinandPhenacemi
de:

Theyarecogener
sofphenyt
oinandli
kewi
seappearmostef
fect
iveagai
nstgener
ali
zedt
oni
c-
cl
onicsei
zur
esandpar
ti
alsei
zures.

Ethot
oinhaslesstoxi
cit
yandadv erseeffect
st hanphenyt
oinsomaybeusedf
ort
hosewi
th
hy
persensi
ti
vi
tytophenyt
oin.Howeveritappearstobealesseff
ect
ivedr
ug.

Like phenyt
oin,bot
h ethot
oin and mepheny
toin exhi
bitsatur
abl
e met
abol
ism withi
nt he
t
herapeuti
cdosagerange.Mephenytoi
nismet abol
izedtonirv
anol(5,
5et
hyl
phenyl
hydantoi
n)
whichisr esponsi
blef
ormostoftheanti-
sei
zur
eacti
vit
yofthi
sdrug.Theyar
eexcr
etedaf
ter
hydroxy
lation and conj
ugat
ion. Ther
apeut
ic l
evel
s are 5-
16mcg/ml and 25-
40mcg/
ml
respect
ively.

3.CARBAMAZEPI
NE

I
tisatri
cycli
ccompoundr
elat
edt
oant
idepr
essant
ssuchasi
mipr
ami
neandi
sef
fect
ivef
or
bi
pol
ardepressi
on.

Mechani
sm ofAct
ion

As wit
h phenyt
oinitblocks Na channel
s atther
apeut
ic concent
rat
ions and inhi
bit
s high
fr
equencyrepet
it
iveneur
onf i
ri
ng.Ithaspresynapt
icact
ivi
tybywhichi tdi
mi ni
shessy napti
c
tr
ansmissi
on

Cl
ini
calUses

I
thaslongbeenadrugofchoiceforbothparti
alandtonic-
cloni
cseizures.I
tisnotsedati
veat
ther
apeut
icr
angeand hasgoodtherapeut
icacti
vi
tyi
nt r
igeminalneural
giaandbipol
ardisorder
pati
ent
s.

Phar
macoki
net
ics

Rateofabsor
ptionwil
lvaryfrom onepersontoanot
herandser
um l
evel
speakby6-
8hr s.The
rat
eofabsorpti
onisreducedi fgi
venaft
ermealsandthi
scanbeusedtosl
owabsorpt
ionand
enabl
epati
entstotol
erat
elargertotal
dai
lydoses.

I
thasaslowdistr
ibut
ionandver
ylowsyst
emiccl
ear
ance.Wi
thcont
inuoust
her
apyt
hehal
fli
fe
of36hour
sdecreasestoaslowas8to12hour
s.

Ther
apeut
icl
evel
sandDosage

I
tcanonlybegivenor
all
yadosageof15t
o25mgperkgperdayi
sappr
opr
iat
einchi
l
drenwhi
l
e
1-2garetol
erat
edbyadult
s.
Dr
ugI
nter
act
ions

Carbamazepinehasenzymeinduci
ngpropert
iesandwillcauseanincr
easedrat
eofmetabol
ism
ofseveraldr
ugsforexamplepri
midonephenytoi
n,et
hosuximide,
valpr
oicaci
dandcl
onazepam .
Protei
nbindi
nginter
acti
onsarenotcl
ini
cal
lysigni
fi
cant
.

Toxi
cit
y

Diplopiaandat axi
aar ethemostcommondoser el
atedadverseef f
ects,
other sincludemi l
dGI T
upset ,
unsteadinessathigherdosesanddr owsiness.Hy ponatr
emi aandwat erintoxicati
onhav e
beenr eport
ed.I di
osyncrat
icblooddy scrasiasareacauseofconcer nandi ncludef atalapl
ast i
c
anaemi aandagr anulocyt
osisocccur i
ngmost lyinelderlypatientswithtrigemi nalneuralgia,
especiallyint hef i
rstfourmont hsoft reat
ment .Some pat i
ent sdemonst r
ate a mi l
d and
persistentleukopeniawhichcanbemoni toredastreatmentcont i
nues.Eryt
hemat ousskinr ash
i
st hemostcommoni di
osyncr
aticreacti
on.

4.PHENOBARBI
TAL

Thisistheol destanti
-sei
zuredr
ugcurrentl
ybei
ngusedandisconsi
der
edtobeoneofthe
safestagents,howeverithassedat
iveeffect
sandmanyareoftheopi
niont
hatt
heyar
ethe
drugofchoiceininf
antsalone.

Cl
ini
calUses

Iti
susedt otreatpar
tialsei
zur
esand general
izedtoni
c-cl
onicseizur
es.I
tisal
sooftentrading
ever
y seizuret ype especi
all
yt hose thatare dif
fi
cultt o contr
ol,t
he eff
ecti
veness of
phenobarbit
alinsomeoft hesegeneral
i
zedseizurecondit
ionssuchasabsenceatonicattacks
andInfanti
l
espasmshasnotbeenconf i
rmed.
5.PRI
MIDONE

Pri
midoneismet
abol
i
zedt
ophenobar
bit
alandpheny
lmet
hyl
mal
onami
de.Al
loft
hesehav
eant
i-
sei
zureef
fect
s.

Cl
ini
calUses

I
tisusefuli
nparti
alsei
zur
esandmaybemor
eef
fect
ivet
hanphenobar
bit
alf
orgener
ali
zed
t
oni
c-cl
onicsei
zur
es.

Phar
macoki
net
ics

I
tis absor
bed compl
etel
y and peak concent
rat
ion occur
sin about3 hour
s af
teror
al
admi
nist
rat
ion.

Ther
apeut
icLev
elsAndDosages

Primi
doneshouldbecommencedatl owdosesandincr
easedgr
adual
l
yov
ert
imet
oreducet
he
occur
renceofpr
onouncedsedat
ionandGITcomplai
nts.

6.GABAPENTI
NANDPREGABALI
N

Gabapenti
nisanami noaci
dandananalogueofGABA.Theymaymodi f
yreleaseofGABAand
causeincr
easeinbrainGABAconcent
rat
ion.Theybi
ndavidl
ytov ol
tagegatedCa2+channel
s
anddecreaseCa2+ent r
yleadi
ngtoadecreasedrel
easeofglut
amat einthesynapseandso
produci
ngtheant
iepi
lept
iceff
ect
.

Cl
ini
caluses

Ithasgoodef
fectasanadj
unctagai
nstpar
ti
alsei
zur
esandandgener
ali
zedt
oni
c-cl
oni
c
sei
zur
esatupt
o2400mgperday.

I
tcanbeusedf
ort
het
reat
mentofposther
pet
icneur
algi
aandneur
opat
hicpai
n.
I
tisanor
alf
ormul
ati
ononl
y,dosagei
sfr
om 150-
600mg/
din2or3di
vi
deddoses.

Phar
macoki
net
ics

I
tisnotmet aboli
zed,
doesnoti nducel
iverenzymesandi
snotboundt opl
asmaprot
einsithas
ver
yl i
tt
ledrug-drugint
eract
ion.Itis excret
edrenal
l
yand unchanged.Half
-Li
fei
sf r
om 5-8
hoursanditisadmini
ster
edto2- 3ti
mesaday .

Pr
egabal
i
nhal
fli
fei
sabout4.
5to7hour
sandsoi
tmustbeadmi
nist
eredmor
ethanoncedai
l
y

7.LACOSAMI
DE

I
tisanami
noaci
drel
atedcompound

Mechani
sm OfAct
ion

I
tenhancest
hesl
owi
nact
ivat
ionofv
olt
agegat
edsodi
um channel
s.

Cl
ini
calUses

I
tisusedasanadj unctintreat
mentofpar
ti
alonsetsei
zuresi
npatient
s16y ear
sandabove.
Dosagei
stwice-
dail
ybeginni
ngwi t
h50mgincreasedby100mgincr
ementsperweek.I
tmaybe
gi
venivf
orshortdurat
ions.

Phar
macoki
net
ics

When admi nistered orall

yi tisrapidl
yand complet
elyabsorbed and has no food ef
fect
,
bioavai
labil
it
yi sal mosthundr edpercentandpeakconcent
rat
ionwilloccurfr
om 1t o4hour s
afteroraladmi nistr
ation.Eli
minat
ionHal f
-Li
fei
s13hours,t
herearenoact i
vemet abol
it
esand
exhibi
tsmi nimal proteinbindi
ng.
C)DRUGSUSEDI
NGENERALI
ZEDSEI
ZURES

Et
hosuxi
mide,
val
proi
caci
d,sodi
um v
alpr
oat
eoxazol
i
dinedi
ones

1.ETHOSUXI
MIDE

I
tisef
fect
iveagai
nstabsencesei
zur
es.I
thasanar
rowspect
rum ofcl
i
nical
act
ivi
ty.

Cl
ini
caluses

I
tispar
ti
cul
arl
yusef
uli
nthet
reat
mentofabsencesei
zur
es

Phar
macoki
net
ics

Fol
lowingadmini
str
ati
oniti
scomplet
elyabsor
bed.Peakl
evel
soccur3-7hoursaft
eror
alint
ake
anditi
snotprotei
nbound.I
tiscompl
etel
ymet abol
i
zedbyhydr
oxylact
ion.Hal
f-
Lif
eisabout40
hours

Toxi
cit
y

Adv
erseeff
ectsi
ncludegastri
cdistressmanifest
ingaspai n,nauseaandvomi
ti
ng.Ot
her
s
i
ncl
udetr
ansi
entl
ethargyorf
ati
gue,headache,
dizzi
ness,
hiccupandeuphori
a.

2.VALPROI
CACI
DandSODI
UM VALPROATE

Iti
sver
yeffect
iveagai
nstabsencesei
zur
es,cancont
rolsomet
ypesofmy
ocl
oni
csei
zur
esand
canbeusedforabroadspectr
um ofsei
zuret
ypes.

I
ti swellabsorbed wit
hbi oavai
labi
li
tygr
eat
erthan 80% afteror
alint
ake.Wit
hin 2 hour
s
achi
evespeakbloodl ev
els.Absorpti
onmaybedelay
edbyf oodanditmayexhi
bitdecr
eased
toxi
cit
yifgi
venaft
ermeal s.I
tis90%boundtopl
asmapr ot
ein.
Dosage

Dosesof25-
30mg/
kg/
dayandev
enupt
o60mg/
kg/
dayar
eut
il
ized.

Dr
ugI
nter
act
ions

I
tdisplacespheny
toi
nf rom plasmaprotei
nsandinhi
bit
sthemet
abol
i
sm ofsev
eraldr
ugs
i
ncl
udingphenobar
bit
al,
phenytoinandcar
bamazepi
ne.

Toxi
cit
y

Mostcommonl ynausea,vomit
ing,abdominalpai
nandheartbur
n.Treat
mentshouldbestar
ted
ver
yslowlytomini
mizetheseeffects.Asmallnumberofpat
ient
stheymayexhibi
tweightgain,
i
ncreasedappet
it
eandhairloss.

Hepatotoxi
cit
ymayoccurandi smorel
ikel
yinpati
entsbel
ow t
woy ear
sofageandthoseon
mult
iple medi cati
ons. Moni
tori
ng of li
ver f
uncti
on is advi
sed, i
t may al
so cause
t
hrombocy t
openi a.

OTHERDRUGS

BENZODI
AZEPI
NES

Diazepam i
sv er
yeff
ect
iveint
rav
enousl
yorr
ect
all
yforst
oppi
ngcont
inuoussei
zur
eact
ivi
ty
especial
l
ystat
usepi
l
epti
cus.

Lor
azepam maybel
ongeract
ingandmor
eef
fect
ivet
handi
azepam.
Clonazepam iseffect
iveagai
nstabsencesei
zures,i
nsomecasesofmy
ocl
oni
csei
zur
es.I
t
causesmar kedsedati
onthusstar
ti
ngdoseshoul
dbesmall
.

Pr
onouncedsedat
ionandt
oler
ancel
i
mitt
heuseoft
hebenzodi
azepi
nes.

CLI
NICALPHARMACOLOGYOFANTI
-SEI
ZUREDRUGS

Seizur
esarediv
idedintoparti
alandgeneral
izedandt
hespeci
fi
ctr
eat
mentwi
l
ldependont
he
ty
peofseizur
edisorderthatt
hepati
enthas.

PARTI
ALSEI
ZURES

Thisoccurswhenthere'salocali
sedonsetofaseizureatt
ack.Di
agnosi
sismadeei
therby
cl
ini
calobser
vat
ionorelect
roencephal
ogr
aphi
crecor
dings.

Theyar
edi
vi
dedi
ntodi
vi
dedi
ntot
hree

a)Si
mpl
epar
ti
alsei
zur
e

Shows mini
malspr
ead ofabnor
maldi
schar
ge wi
th pr
eser
vat
ion ofconsci
ousnessand
awareness

b)Compl
expar
ti
alsei
zur
eand

Local
ized i
n onsetbutsubsequent
lyspreadi
ng t
oinv
olv
eot
herbr
ainr
egi
ons,nor
mal
l
y
bi
l
ateral
andf r
equentl
yinv
olv
ingthel
imbicsy
stem.

c)Secondar
il
ygener
ali
zedsei
zur
e

Thi
sist
hecasewher
eapar
ti
alsei
zur
epr
ecedesagener
ali
zedt
oni
c-cl
oni
csei
zur
e.
GENERALI
ZEDSEI
ZURES

I
nthi
sty
peofsei
zur
ether
eisnoev
idenceofl
ocal
i
sedonset
.

1)Gener
ali
zedt
oni
c-cl
oni
csei
zur
es:

Thereisini
ti
altonicrigi
dit
yfoll
owed byv i
olentgener al
ized jerki
ng ofthebody,normally
fol
l
owed byast uporousphase.Theremaybebi ting oft het ongueorcheekandur inary
i
nconti
nenceiscommon.Pr imar
ygeneral
izedt oni
c-cloni
csei zuresbeginwit
houtev
idenceof
l
ocali
sedonsetwhi l
esecondarygener
ali
zedt onic-
cl oni
csei zuresareprecededbyanot her
sei
zurety
peusuall
yapar t
ial
sei
zure.

2)Absencesei
zur
e

Alsoknownaspeti
tmalandshowssuddenonsetandabr uptter
minat
ion.I
trar
elylast
slonger
than45secondsandi
sassociatedwithal
ter
edconsciousnessandtheremaybemi l
dclonic
j
erkingoft
heeyel
i
dorext
remi
ties,aut
omati
cal
lyorcal
li
tmayoccurof200x100t i
mesaday

3)My
ocl
oni
cjer
king

Occur
sinv
ari
oust
ypesofsei
zur
es.

4)At
oni
csei
zur
es

Invol
vesuddenlossofpost
uralt
one.Thepat
ientmayf
allt
othef
loorsuddenl
y,i
fst
andi
ngand
i
tismostoftenseeni
nchil
dren.

5)I
nfant
il
espasms

arenotat ypeofseizur
e.Theyaredescribedasanepilept
icsyndrome.Theyof t
eninvol
ve
bi
lat
eralbr
iefrecur
ri
ngmy ocl
oni
cjer
koft hebodywit
hsuddenf l
exi
onext ensi
onofthet
orso
andli
mbs.Thecauseisunknownanditsassoci
atedwi
thcognit
iveret
ardat
ion
THERAPEUTI
CSTRATEGY

Monotherapyispreferr
edasithasfeweradver
seeffect
s.Inhardtocontr
olsei
zuresmul t
ipl
e
drugsmayber equi
red.Mostant
i-
seizur
edrugshavelow t
her
apeuti
cindexandt oxi
cit
yisnot
uncommon.Ef fecti
veseizur
emanagementr equi
resaknowl edgeofthet her
apeuti
cl ev
els,
pharmacokinet
ics.

MANAGEMENTOFEPI
LEPSY

1PARTI
ALSEI
ZUREANDGENERALI
ZEDTONI
C-CLONI
CSEI
ZURE.

Theolderagent
shav eahi gherconfidencelev
elthantheneweragent ssimplybecauset hey
hav
ebeenar oundf ormuchl ongerandconsequentlytheireffi
cacyandl ong-
ter
m effect
sar e
wel
lknown.Howev ertheneweragent shaveabroaderspect r
um ofacti
vi
tyandagoodnumber
oft
hem arewellt
olerated,
fort hi
sreasontheyareoft
enpr efer
redtotheolderagents.

2.GENERALI
ZEDSEI
ZURE

Ethosuxi
mide,v
alpr
oateandclonazepam ar
eef
fect
iveagai
nstabsencesei
zur
es.Lamot
ri
gine
andtopir
amatemayalsobeuseful.

My
ocl
oni
csy
ndr
omes:
val
proat
e,cl
onazepam,
nit
razepam (
andot
herbenzodi
azepi
nes)

Juv
eni
l
emy
ocl
oni
cepi
l
epsymaybewor
senedbypheny
toi
norcar
bamazepi
ne

Atonicsei
zur
esar enormall
yunresponsi
vet
oallagentst
houghval
proat
eandlamotri
ginemay
beusefulforthi
s.Lossoft onemaybeduet oanothersei
zur
etype(egabsenceorcompl ex
part
ialsei
zures)t
hisshouldbet reat
edasv i
gor
ouslyaspossi
blewiththehopethatatonic
componentmayal soresol
ve.

3.I
NFANTI
LESPASMS

Treat
mentopti
onshereareunsati
sfact
oryasotherfeaturesofthedisorderegr et
ardat
ion
cannotbeal
l
evi
ated.Agent
sut
il
izedincl
udei
m cort
icot
ropin,pr
edni
sone,benzodi
azepi
nesand
vi
gabatr
in
4.STATUSEPI
LEPTI
CUS

Thi
shasv ari
ousfor
ms.General
izedt
onic-cl
onicst
atusepi
lept
icus,
themostcommonf or
m, i
sa
l
if
e threateni
ng emergency and requires immediat
e CVS, r espi
rat
ory and metabol
ic
managementalongwit
hpharmacologi
ct herapy
.

I
nmostcasesdi azepanisthemostef fect
iveagentwithamaximum tot
aldoseof20-30mg
gi
venbyi nt
rav
enouspushi nadults.Faci
li
ti
esforresusci
tat
ionmustbeavai
l
ablewhenthisis
ut
il
ized.Theef
fectsaretemporar
yandpr ovi
deabreathi
ngspaceformorel
ast
ingint
erv
ent
ions.

I
vpheny toinmaybeadmi ni
steredasal oadi
ngdoseat13-18mg/kgi nadult
satamax i
mum
rateof50mg/ min.Itmaybeadmi ni
stereddi
rect
lyori
nsali
ne.I
twillpreci
pit
aterapidl
yinthe
presenceofglucose.Car
diacrhythm andBPmustbeclosel
ymonit
oredespeciall
yintheelder
ly.
Fosphenytoinmayalsobeutil
ized.

I
npat i
ent
sunresponsi
vetophenyt
oin,phenobar
bit
al100-
200mgI
vmaybegivenuptoatotal
doseof400-800mg.Respir
ator
ydepressionisacommoncompli
cat
ionwi
tht
hisregi
menand
wil
lpossi
blyr
equi
reint
ubat
ionandventi
lat
ion.

Gener
alanaest
hesi
aisusual
l
yrequi
redi
next
remel
yresi
stantcases.
.

TERATOGENI
CITY

Chi
ldr
enborntowomenwhoar eonantiepi
l
epti
cmedi
cat
ionhav
eani
ncr
easedr
isk,
possi
blyup
tot
wofol
d,ofsuf
fer
ingf
rom congeni
tal
malfor
mati
on.

I
tisgener
all
yagreedt
hatgr
avi
dpat
ient
sshoul
dbet
reat
edwi
tht
hemi
nimum ef
fect
ivedoseof
ant
i-
sei
zuredrug.

WI
THDRAWAL

Wit
hdrawalofanti
-sei
zur
edr
ugsi
nepi
l
ept
icpat
ient
scanpr
eci
pit
atei
ncr
easedf
requencyand
sev
eri
tyofsei
zures.

Ant
iabsencedr
ugsar
emor
eeasi
l
ywi
thdr
awnt
hant
hosef
orpar
ti
alorgener
ali
zedt
oni
c-cl
oni
c
sei
zur
es.

Bar
bit
urat
esandbenzodi
azepi
nesar
ethemostdif
fi
cul
ttoter
minat
eandsuccessf
ulwi
thdr
awal
maytakeweeksormonthsofver
ygr
adual
dosereduct
ion.
OVERDOSE

Thesedr ugsareCNSdepressant
sbutar
erar
elyl
ethalr
equi
ri
ngv
eryhi
ghbl
oodl
evel
sto
approachli
fe-
thr
eat
eni
ngov
erdose.