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Antiseizure
(antiepileptic)
drugs
(Abstract)
Assoc. Prof. Ivan Lambev
e-mail: itlambev@mail.bg
EEG
Cortex:
F frontal
O occipital
T temporal
Rang
Rangetetal.
al.
Pharmacology
Pharmacology
55ththEd.
Ed.(2003)
(2003)
Classification of seizures
HISTORY
Bromides (1857)
Phenobarbital (1912)
Phenytoin (1938)
Later: Ethosiximide, Carbmazepine
New anticonvulsants (in the last 1520 years):
vigabatrin, gabapentin, lamotrigine, topiramate,
oxcarbazepine, levetiracetam, pregabalin etc.
ANTISEIZURE DRUGS
intoxication too
3. Barbiturates (Phenobarbital enzyme inductors) and their
analogues (Primidone prodrug)
4. Succinimides: Ethosuximide (casp. 250 mg petit mal)
5. Valproates (enzyme inhibitors): Sodium valproate (Depakin)
6. Benzodiazepines: Clonazepam, Clorazepate, Diazepam
t1/2 43 h, amp. 10 mg/2 ml i.m./i.v., Lorazepam, Nitrazepam
7. GABA analogues: Gabapentin, Tiagabine
8. Hetereogenic anticonvulsants: Lamotrigine, Levetiracetam,
Pregabalin (partial seizures, peripheral neuropathic pain),
Topiramate, Vigabatrin
GABA
GABA
Barbiturates
Benzodiazepines
Gabapentin
Levetiracetam
Tiagabine
Topiramate
Valproate
Vigabatrin
Na++
Na
Carbamazepine
Lamotrigine
Oxcarbazepine
Phenytoin
Topiramate
Valproate
Ca2+2+
Ca
Ethosuximide
Levetiracetam
Pregabalin
Valproate
Antiseizure drugs
enhanced
GABA
synaptic
transmission
Goodman
Goodman&&Gilman's
Gilman's
The
ThePharmacologic
PharmacologicBasis
Basisofof
Therapeutics
Therapeutics- -11th
11thEd.
Ed.(2006)
(2006)
Goodman&&Gilman's
Gilman'sThe
ThePharmacologic
PharmacologicBasis
BasisofofTherapeutics
Therapeutics11
11ththEd.
Ed.(2006)
(2006)
Goodman
INDIVIDUAL ANTIEPILEPTICS
CARBAMAZEPINE blocks voltage-dependent sodium ion channels,
reducing membrane excitability. The t1/2 of the drug falls from 35 to
20 h over the first few weeks of therapy due to the induction of hepatic
enzymes that metabolize it as well as other drugs (including adrenal
corticosteroids, hormonal contraceptives, theophylline and warfarin.
Standard tablets are taken twice a day. Carbamazepine is a drug of
first choice for focal and secondary generalized epilepsy but
aggravates myoclonic and absence seizure. It is useful for the
treatment of trigeminal neuralgia, postherpetic pains, etc.
Adverse reactions (ARs): reversible blurring of vision, diplopia,
dizziness, ataxia, depression of AV conduction, skin rashes, liver, and
kidney dysfunction.
Saturation kinetics. Phenytoin is extensively hydroxylated in the liver and this process becomes
saturated at about the doses needed for therapeutic
effect. Thus phenytoin at low doses exhibits firstorder kinetics but saturation or zero-order kinetics
develop as the therapeutic plasma concentration
range (1020 mg/L) is approached, i.e. the dose
increments of equal size produce disproportional rise
in steady-state plasma concentration.
Basic
Basic&&Clinical
Clinical
Pharmacology
Pharmacology
th
10
10thEd.
Ed.(2007)
(2007)
BENZODIAZEPINES
Diazepam given intravenously or rectally is highly effective for
stopping continuous seizure activity, especially generalized tonicclonic status epilepticus. The drug is occasionally given orally on
a long-term basis, although it is not considered very effective in
this application, probably because of the rapid development of
tolerance. A rectal gel is available for refractory patients who need
acute control of bouts of seizure activity.
Lorazepam appears in some studies to be more effective and
longer-acting than diazepam in the treatment of status epilepticus
and is preferred by some experts.
Clonazepam (t1/2 25 h) is a benzodiazepine used as a
second line drug for treatment of primary generalized epilepsy
and status epilepticus.
Clonazepam, Clorazepate,
Diazepam, Lorazepam,
Nitrazepam
GABAAbenzodiazepine
receptor
complex
By
ByBennett
Bennettand
andBrown
Brown(2003)
(2003)
s
Z
BD te
si
GABA
GABAAsite
+
Cl
+ Barbitu-
rate sate
Barbiturates
Basic
Basic&&Clinical
Clinical
Pharmacology
Pharmacology
th
10
10thEd.
Ed.(2007)
(2007)
StevensJohnson syndrome
PRINCIPLES OF MANAGEMENT
(Clinical Parmacology 9th Ed., 2003)
Any causative factor must be treated (cerebral neoplasm etc).
Educate the patient about the disease, duration of treatment
and need for compliance.
Avoid precipitating factor (alcohol, sleep deprivation, emotional
stress, and caffeine).
Anticipate natural variation: fits may occur around menstrual
periods in women catamenial (monthly) epilepsy.
Give antiepileptics only if seizure type and frequency require it
(e.g. more than one fit every 612 months).
Alternative methods
for treatment of epilepsy:
Neurosurgery +
laser therapy