Phåsie Brid Textbook of Pharmacology for
Physiotherapy
ANTICONVULSANTSATI-EPICEPTIC DEUGS Studera
prophylaxis and control off convulsions.
Anticonvulsants are the drugs, which are uscdfor
isa more preiseterm inthis regard. "convulsions"
Epilepsy isa Greck word, which mcans
are "repeated, involuntary and violent muscular contraction and relaxation"
"Antiepilepikt
an convulsions
Theuncontrolled shaking of the body. The convulsion is often asymptom of an epileptic eizure.
Convulsion
Seizure is asudden discharge ofused
word is sometimes as a synonym
excessive
for "seizure"
resuting
electrical energy from nerve cells located within the brain,
called "epilepsy'
The
However, not episodes
recurrent of such
all epileptic seizures leadare
seizures to convulsions and not all convulsions are caused by egileg
seizures.
language to describe epileptic seizure.
The word "it/fits is often used in common
MUST KNOW
Epilepsy is the most prevalent neurological disorder and affects about 1% of world population. It is not asingje
disease but a collection of different syndromes characterized by the same feature. The episodes of epilepsy are
variable.
highly unpredictable and the frequency is also
Classification of Seizures
Seizures are classified on the basis of case history, clinical manifestations and the findingsd
electroencephalogram (EEG).
deciding the treatment line for the ive
Accurate diagnosis of the type of seizure is very important for
and to prevent future episodes of seizures. Table 4.20 and Figure 4.3.
Seizures have been classified into various types as given in
Antiepileptic Drugs
do not cure the disease.
Antiepileptic drugs are given to control the seizures but, they
long-term goals.
The goals of antiepileptic therapy are both short-term and deleterious effects fron
Short-term goal is to provide immediate neuroprotection by minimizing
seizure attacks.
seizure attacks.
Long-term goal is to provide the prophylactic therapy to prevent the future episode, ie., a3-yer
seizure
Fhe antiepileptic therapy is usually continued for 3 years after the last
seizure-free period is mandatory for stopping the treatment.
Classification
Cassification of antiepleptic drugs is given in Table 4.21.
The mechanísm of action of all the above drugs has been categorized into three types as given in labic
Barbiturates
Phenobarbitone
This was the first efficacious antiepileptic drug, which was introduced in 1912.
It is still in use due tocost-effectiveness and least toxicity.
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Textbook of Pharmacologytor
Table &21: Claseification of antiepileptic drugs
Physiotherapy Stuyden
Cass Drugs
Rarhiturates Phenobarbitone
Deoxybarbiturate Primidone
Hydantoin
Phenytoin, fosphenytoin
Carbamazepine, oxcarbazepine
Iminostitbenes
Succinimide Ethosuximide
Aliphatic carboxylic acid Valproic acid (sodium valproate), divalproex
Clonazepam, diazepam, lorazepam
Benzodiazepines
Phenyltriazines Lamotrigine
Gabapentin, pregabalin
Cyclic GABA analogs
Topiramate, zonisamide, levetiracetam, , vigabatrin, tiagabine,
Newer drugs lacosamide
action and their respective drug classes
Table 4.22: Categories of mechanism of
Drug/drug classes
Mechanism of action
Barbiturates, benzodiazepines, sodium valproate,
Potentiation of GABA-mediated chloride channel gabapentin, vigabatrin, tiagabine
brain and
opening leading to inhibitory effects in the
control of convulsions
channels Phenytoin, sodium valproate, fosphenytoin,
Prolongation of inactivated state of sodium carbamazepine, oxcarbazepine, lamotrigine, topiramate
zonisamide, lacosamide
Ethosuximide, sodium valproate, zonisamide
Inhibition of T-type calcium current
indicated for the treatment of hyperbilirubinemia in neonates. It increases the activitr &
It is also
bilirubin; thereby helping its excehim
conjugation of
glucuronyl transferase enzyme and causes fast
through bile.
mg OD-TDS orally and 100-200 mg IM/IVin adults and 3-6 mg/kg/day in childrm
It is given in adose of 60
The major side effects are: hyperactivity in children
CNS: Ataxia, drowsiness, learning difficulties,
Eye: Nystagmus
Skin: Rashes.
drowsiness.
After prolonged use, tolerance develops to
Deoxybarbiturate
Primidone
liver to its active metabolites phenobarbitone and phenylethylmelonamiR
It is metabolized in the
(PEMA).
phenytoin.
Itis converted to phenobarbitone but the action simulates
It is indicated in generalized tonic-clonic and partial seizures.
10-20 mg/kg/day in children.
It isgiven in a dose of 250-500 mg BD for adult and
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Rghto Brd
topkes
major side effects are:
The ma
CNS:
Sedation, ataxia, irritability
Eyes, nose and throat (ENT):
(GIT: Nystagmus,vomiting
Gastrointestinal tract
Skin: Rashes. Nausea, vertigo
Mdentoin
Phenvtoin
isthe oldest
nonsedative
antiepileptic drug.
Its antiepileptic activity is due to
mechanisms:
tdelays the recovery of
stabilization of the neuronal membrane by the following three
tblocks the activated inactivated sodium channels.
2
nblocks the high sodium channel alsO.
3.
trequency firing in neurons.
ts absorbed slowly but
binding. completely when given by oral route with approximately 90% plasma
is also a potent microsomal enzyme protein
his never given by
inducer.
he absorption ntramuscular route as the drug
precipitates in the muscles, causes pain and makes
unpredictable. It causes
Fosphenytoin can be given by both IV andthrombophlebitis and hypotension when given by IV
is indicated in IM routes. route.
generalized
The other uses are in the tonic-clonic, partial seizures and
treatment of trigeminal neuralgiastatus
(the
epilepticus.
first choice is carbamazepine) and
ventricular arrhythmia due todigitalis toxicity.
. tis given in dose of 100-200 mg BDoral and 25
a
5-8 mg/kg/day in children mg/min slow IV injection (max. 1.0 g) in adults and
(fosphenytoin is preferred for parenteral use).
Phenytoin has dose dependent adverse effects.
The adverse effects seen after prolonged use
even when the plasma levels of drug are
therapeutic range (10-20 ug/mL). maintained within
Gum hypertrophy
Hirsutismn (in females) and acne
Hyperglycemia
Osteomalacia and hypocalcemia
Megaloblastic anemia
If used during pregnancy "fetal hydantoin syndrome" is
produced, which is characterized by cleft
palate, cleft lip, digital hypoplasia, microcephaly and congenital
The adverse effects seen heart disease.
when the plasma levels of drug exceed >30 ug/mL are:
CNS: Ataxia, metal confusion and disorientation
ENT: Vertigo, diplopia, nystagmus
Cardiovascular system: Hypotension and cardiac arrhythmia, when given by IV route in higher
dose or at a very fast rate.
GIT: Nausea, vomiting and
dyspepsia.
Fus" ptishenytaoin phenytoin and is
dose ofprodrugof
25-100 mg/min IV injectionrapidly converted to phenytoin after IV administration. It is givenin a
(max. 1.0 g) for status epilepticus.
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hpsie Bril Textbook of Pharmacology for
t
following advantages over phenytoin:
Physiotherapy Stuemy
Ithas the cardiotoxic.
and less
It is more potent
GII.
It is safe on the
by both IV andIM routesand damage to intima off vessels is very less.
can be
ItIt can given withbothsaline andglucose. The slightly faster infusion rate is tolerable
be iniccted
be safely used in emergency such as status epilepticus.
It can
Iminostilbenes
Carbamazepine antiepileptic drugs.
t acts like most commonly
phenytoin
the by used
blocking the sodiumchannels and inhibiting the high frequency firing oí
It is one of
neurons in the brain. microsomal enzyme inducer.
is a powerful
andphenomenon seen with carbamazepine, in which it reduces its own hal
is given by oralisroute
ItAutoinduction special
hours due to enzyme induction.
from 30-36 hours to 8-12
It is indicated in:
GTCS
seizure
Simple and complex partial choice)
Trigeminal neuralgia (drug of
Chronic neuropathic pain
alternative to lithium)
Bipolar mood disorder (as an adults and 15-30 mg/kg/day in children.
mg TDS in
It is given in a dose of 200-400
The major adverse effects are: exacerbate myoclonic seizure
CNS: Ataxia, drowsiness and may
GIT: Nausea, blood dyscrasias
Skin: Stevens-Johnson syndrome
Eye: Nystagmus, diplopia
Oxcarbazepine over it.
similar to carbamazepine in actions and uses with the following advantages
Itis
Few hypersensitivity reactions
low autoinduction phenomenon,
Weak microsomal enzyme induction and
L Low hepatotoxicity
Better tolerated
" It is given in a dose of 300-600 mg BD.
Succinimide
calciumcutt
Ethosuximide
drugs by reducing the low threshold
I acts differently from other antiepileptic
(T-current) in thalamocortical system.
of absence seizure.
These Tcalcium-currents are responsible for the generation
Itis completely absorbed when given by oral route.
Absence seizure is the only indication of this drug. Valproic acid is preferred.
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D nge Moy Cotent
tisgiven in a dose of 20-30
1he maiot adverse effects are:
GIT: Nausca, vomiting and
mg/kg/day.
CNS: Headache, lethargy, blood dyscrasias
Skin: Systemic lupus unsteadiness
Aliphatic Carboxylic Acid
erythematosus, urticaria, pruritus.
alproic Acid (Sodium Valproate)
Valproic acidis avery effective and
It is also known as broad-spectrummost widely useddueantiepileptic agent.
disorders. antiepileptic to its effectiveness in many types of epileptic
hacts at multiple sites and its action resembles both
Itinhibits the Ttype Ca' current, delays the recovery ethosuximide and phenytoin.
ofinactivated Na' channels and increases the GABA
activity.
It has rapid and neary complete oral absorption. 80-95% is plasma protein
liver and excreted in urine.
bound. It is metabolized in
Itis used therapeutically in the following conditions:
Myoclonic and atonic seizures
Absence seizures
Combined grand mal and petit mal epilepsy
Focal epilepsy
Manic depressive psychosis
Prophylactically in febrile convulsions and migraine
As an alternative to carbamazepine in trigeminal neuralgia.
Its main side effects are:
GIT: Nausea, vomiting, astritis and occasionally loose motions
CNS: Ataxia, sedation
Increase in appetite, weight gain and curling of hair can be seen.
ldiosyncratic hepatotoxicity can also occur in children; monitoring of liver functions should be done
regularly.
It is teratogenic and can cause neural tube defects like spina bifida.
To begin the treatment, it is given in adose of 10 mg/kg/day in two to three divided doses and gradually
increased by 5-10 mg/kg/day at weekly intervals up to amaximum dose of 20-30 mg/kg/day.
It is an inhibitor of hepatic microsomal enzymes and can increase plasma levels of phenobarbitone,
phenytoin, carbamazepine and lamotrigine.
Divalproex
Itis achemically compounded form of valproic acid with sodium valproate having actions and therapeutic
uses similar tovalproic acid.
It has the following advantages over sodium valproate:
Ithas slow rate of absorption.
Better gastric tolerance,
Better bioavailability.
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Texthook of Pharmacology for
Physiothers
Renzodinzepines
Oonazepam, Diarepam, Iorazepam) such as tatus
Benzodinzeines are used for short termcontrol of epilepsy epilepticus
and ae
choe for the long term treatment of epilepsies. not
ofthe BZDs Used as anticonvulsants
Diazepam, cdonazepam and lorazepam are some is preferred in
iin
statius
epile
Rectal route
Diarepamis given by both IV route and rectally.injection febrile
Iis given in a dose of (0.2-0.3 mg/kg by slow
IV in status epilepticus and o05 convalsieng
in febrile convulsions.
Lorazepam can also be usedin statusepilepticus in adose of 0.1 mg/kg IVV(slow injection). mg/kgrerta
Phenyltriazines
Lamotrigine
CEY
nMPNENTARY
It is a new broad -spectrum antiepileptic drug.
Its actions resemble carbamazepine.
metabolized in liver.
It is completely absorbed orally and other drugs in partial seizures, generalized
It can be used either alone or in combination with
absence myoclonic
seizure isandstarted seizures.
The treatment with a dose of 50 mg/day. The dose can be increased up to a maximy
300 mg/day.
The major side effects are:
CNS:Sedation, ataxia
Eye: Visual disturbances
Skin: Rashes
GIT: Dyspepsia
It should not be used in children.
Cyclic GABA Analogs
Gabapentin
easily crosses blood-brain barrier.
It is a lipid-soluble analog of GABA, which binding to the L-type voltag z
It enhances the release of GABA and decreases the calcium entry by
calcium channels.
The oral absorption is good.
partial seizures.
It is used in combination with other antiepileptic drugs in GTCS,
Other uses:
Migraine
Neuropathic pain (diabetic neuropathy, postherpetic neuralgia)
Bipolar mooddisorders.
nystagmus. The tolerance usualy dena
The major side effects are fatigue, weight loss, ataxia, sedation,
to these side effects within 1-2 weeks.
Pregabalin
side ettects
Itis a prodrug of gabapentin, which is more potent than gabapentin with less
The pharmacokinetic profile and therapeutic uses are similar to gabapentin.
It is given in a dose of 75-150mg BD.
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The maor side
CNS:
effets are:
Poor
Skin: Rashes,concentration, dizziness, somnolence (less prominent)
oters: Neightanaphylactoid
gain, reactions
Newerdrugs thrombocytopenia.
(Topiramate, Zonisamide,
Levetiracetam,
1hesenewer drugs are used as add-on Vigabatrin,
drugs to other
Tiagabine, Lacosamide)
generalized seizures.antiepileptic agents.
hese are useful both in focal and
Somespecialfeatures of these drugs are given in
Table 4.23.
Table 4.23: Special features of newer antiepileptic drugs
Dose
Drug
Special features
