ANTI-SEIZURE /ANTIEPILEPTIC

DRUGS

(ANTICONVULSANTS)

BY

NAKALEMBE LOYCE
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 DEFINITIONS
Difference between seizure, epilepsy and convulsions

Many believe that having a seizure equates to having epilepsy,

however:-

Seizures-finite episodes of brain dysfunction resulting from

abnormal discharge of cerebral neurons.

Or transient alteration of behavior due to the disordered,

synchronous, and rhythmic firing of populations of brain
neuron

A seizure is a single occurrence

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 DEFINITIONS
Epilepsy-chronic neurological disorder characterized by periodic &
unpredictable occurrence of seizures.

Epilepsy- denotes the occurrence of spontaneous, unprovoked seizures

Convulsions-symptom of epileptic seizure that manifests as a series of

extreme jerky movements of the muscles that repeatedly contract and
then relax

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 Seizures
Three stages of a seizure

Aura – The start of a partial seizure.

• If the aura is the only part an individual experiences, they’ve had a simple
partial seizure.

• If the seizure spreads and affects consciousness, complex partial seizure.

• If the seizure spreads to the rest of the brain, it is a generalized seizure.

Ictus – Meaning stroke or attack, ictus is another word for the physical
seizure.

Postictal – Meaning after the attack, postictal refers to the after effects of the
seizure, e.g., arm numbness, loss of consciousness, partial paralysis, etc.
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 Epidermiology of epilepsy
• Accounts for aprox 1% of the global burden of disease.

• Approximately 50 million people worldwide have epilepsy

• Its 3rd most common neurologic disorder after dementia and stroke.

• Nearly 80% of the people with epilepsy live in low- and middle-

income countries.

• Epilepsy seizures often cause transient impairment of consciousness

leaving the individual at risk of bodily harm.

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 CAUSES OF EPILEPSY
Causes of epilepsy can be put into three main groups:

 Symptomatic epilepsy(known cause), examples include:

• Genetic conditions that result in brain injury, such as tuberous

sclerosis.

• Low oxygen during birth

• Head injuries that occur during birth or from accidents during youth or
adulthood.

• Brain tumors.

• Infections such as meningitis or encephalitis

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Idiopathic epilepsy (has genetic basis-inherited)

• Determines a persons seizure threshold

• Examples: juvenile myoclonic and childhood absence epilepsy, Dravet syndrome

Cryptogenic epilepsy

• Unknown cause

Note: Behavioral manifestation of seizures are determine by the function of

the affected cortical site

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 SEIZURE CLASSIFICATION

• Epilepsy is due to sudden, excessive depolarization of some or all

cerebral neurons.

This may be:

• localized (focal or partial seizure);

• spread to cause a secondary generalized seizure;

• may affect all cortical neurons simultaneously (primary

generalized seizure).

Note: seizure are thought to arise from cerebral cortex and not other
CNS structures.
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CLASSIFICATION OF EPILEPTIC
SEIZURES

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 • BY Goodman and gilman,12th ed

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 • Generalized seizures are the result of abnormal activity in both
hemispheres of the brain simultaneously hence consciousness is lost at
the onset of the seizure.

• Partial (focal) seizures occur when this electrical activity remains in a

limited area of the brain (affect initially only one hemisphere of the
brain)

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 EEG

Cortex:
F – frontal
O – occipital
T – temporal

Rang et al.
Pharmacology
– 5th Ed. (2003)

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Classification of seizures
 PATHOGENESIS OF EPILEPSY
• Recent studies in animal models of focal epilepsy suggest a central
role for the excitatory neurotransmiter glutamate (increased in
epilepsy) & inhibitory GABA (decreased)

• Thus there are two phenomenons in the pathophysiology of a

seizure:-

Hyper-excitability of a neuron.

Hyper synchronization: means that a hyper-excitable neuron leads

to excessive excitability of a large group of surrounding neurons.

• A hyper-excitable neuron cannot generate a seizure alone hence

synchronization is important in seizure occurrence.
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 MECHANISM OF ACTION OF ANTI-
SEIZURE DRUGS
These inhibit the neuronal discharge or its spread in one or more
of the following ways:

(1) Enhancing GABA synaptic transmission:

• The result is increased permeability to chloride ions which

reduces neuronal excitability and raise seizure threshold.

• Examples include: barbiturates, benzodiazepines, gabapentin,

levetiracetam, tiagabine, vigabatrin, topiramate, valproate

• Valproate and topiramate block GABA transaminase &

tiagabine blocks reuptake of GABA.
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Molecular targets for antiseizure drugs at the inhibitory,
GABAergic synapse.
Specific targets
1, GABA transporters(especially GAT-1,
tiagabine)
2, GABA-transaminase (GABA-T, vigabatrin)
3, GABAA receptors (benzodiazepines);,
4, potentially GABAB receptors
5, synaptic vesicular proteins (SV2A)
“nonspecific” targets
such as by voltage-gated (VG) ion channels and
synaptic proteins..
Blue dots represent GABA

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 (2) Modulation of voltage gated ionchannels,Na+,K+,Ca2+

a. Promoting inactivated state of the voltage-gated Na+ channels:

• This limits the sustained and repetitive firing of neurons at high

frequency by reducing the rate at which the channels recover from
inactivation

EXAMPLES; Carbamazepine, lamotrigine, oxcarbazepine,

phenytoin, topiramate, valproate.

b. Reducing cell membrane permeability to calcium T-channels:

• The result is diminishing of the generation of action potential.

Examples: Valproate, ethosuximide, Lamotrigine

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(3) Direct modulation of synaptic release thru effects on cpds of release
machinary, SV2A & α2γ
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(4) Inhibiting excitory neurotransmitter glutamate:AMPA & NMDA
antagonist E.g. felbamate & phenobarbital respectively
• Molecular targets at excitatory, glutamatergic
synapse.

Presynaptic targets diminishing glutamate release

include

1. Voltage-gated (VG) Na + channels (phenytoin,

carbamazepine, lamotrigine, and lacosamide)

2. VG-Ca 2+ channels (ethosuximide, lamotrigine,

gabapentin, and pregabalin)

3. K + channels (retigabine)

4. Synaptic vesicle proteins,SV 2 A (levetiracetam)

5.CRMP-2, collapsin-response mediator protein-2

(lacosamide).

Postsynaptic targets

6. AMPA receptors (blocked by phenobarbital,

topiramate, and lamotrigine)

7. NMDA receptors (blocked by felbamate)

2/10/2020 Ms Loyce EAAT, excitatory amino acid transporter. Red dots 21

represent glutamate.
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 ANTI-SEIZURE MEDICATIONS
HISTORY
• Bromides (1857)

• Phenobarbital (1912)-Use was limited mainly to generalized tonic-

clonic seizure, to lesser degree simple and complex partial seizures

• Phenytoin (1938)-suppressed seizures in absence of sedative effects.

• Later: Ethosuximide, Carbamazepine

• New anticonvulsants (in the last 15–20 years): vigabatrin,

gabapentin, lamotrigine, topiramate, oxcarbazepine, levetiracetam,
pregabalin etc.

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 DRUGS USED IN PARTIAL SEIZURES &
GENERALIZED TONIC-CLONIC SEIZURES

• These include: phenytoin (and congeners), carbamazepine,

valproate,and the barbiturates.

• However, the availability of newer drugs—eslicarbazepine,

lamotrigine, levetiracetam, gabapentin, oxcarbazepine, pregabalin,
retigabine, topiramate, vigabatrin, lacosamide,and zonisamide—is
altering clinical practice in countries where these compounds are
available.

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 1. HYDANTOINS (e.g. phenytoin)
• Phenytoin is the oldest non-sedative anti-seizure drug introduced in 1938 (was
also known as diphenylhydantoin)

• Not effective on absence seizures.

• May also used in status epilepticus that doesn’t respond with BDZ.

• May also be used for certain cardiac arrhythmias or neuropathic pain

MOA

It alters Na+, K+, and Ca2+ conductance, membrane potentials, and the
concentrations of amino acids and the neurotransmitters NE, Ach and GABA

• phenytoin blocks sustained high-frequency repetitive firing of action potentials

by actin on the Na+ channel inactivation
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 PHARMACOKINETICS
• Absorption is highly dependent on the formulation of the dosage form.

• Oral formulations: Rapid release & extended release.

• These differ in PK and dissolution

• Therapeutic level 10-20µg/ml

• Absorption of phenytoin sodium from the GIT is nearly complete.

• Time to peak plasma concentration may range from 3 to 12 hours

IM not recommended
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• Highly bound to plasma proteins(90%) (valproate compete with it

for binding, ↑free drug)

• Drug conc in CSF is proportionate to the free plasma level.

• Accumulates in brain, liver, muscle, and fat.

• Metabolized to inactive metabolites (parahydroxyphenyl derivative-

excreted in urine.

• 95% of phenytoin metabolized in the hepatic ER by CYP2C9/10

and to a lesser extent CYP2C19.

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• Elimination is dose-dependent.

• At very low bld levels, its metabolism follows first-order kinetics

• half-life varies from 12 to 36 hrs

• Much longer half-lives are observed at higher concs.

Drug interactions

• Other highly bound drugs, such as phenylbutazone and sulfonamides,

can displace phenytoin from its binding site.

• It inhibits warfarin metabolism hence increase bleeding & enhances

metabolism of oral contraceptives (CYP3A4).

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 FOSPHENYTOIN
• Phenytoin’s low water solubility hindered its IV use hence fosphenytoin
production.

• Fosphenytoin- more water soluble phosphate

• prodrug of phenytoin, well absorbed after IM admin.

• Converted into phenytoin by liver & RBS phosphatases.

• Half life 8-15 minutes

• Extensively bound (95-99%) to plasma proteins and displaces phenytoin from

protein binding sites.

• Used for adults with partial or generalized seizures when IV or IM admin

in indicated

• Used in emergency treatment of status epilepticus

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 Toxicity
The toxic effects of phenytoin depend on the route of administration, the
duration of exposure & dosage.

• Increased seizure frequency

• GI symptoms

• Gingival hyperplesia-due to folate deficiency

• Megaloblastic anaemia-due ↓folic acid levels.

• Hirsutism in young women (abnormal hair growth on face and body)-

due to hyperandrogenism.

• Hypersensitivity rxns-steven’s Johnson syndrome, mobiliform rash

• Ethotoin may be recommended for patients who are hypersensitive
to phenytoin, but larger doses are required.
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2/10/2020
Stevens–Johnson
Ms Loyce
syndrome 31
 • Hematological rxns include neutropenia & leukopenia

• Long-term use is associated with:

 with coarsening of facial features and with mild peripheral neuropathy

 abnormalities of vitamin D metabolism leading to osteomalacia.

OTHERS: Endocrine effects-hyperglycemia, inhibits insulin secretion-inhibits

Ca2+ release.

• Fosphenytoin causes cardiac arrhythmias with or without hypertension

-CNS depression

NOTE: The incidence of severe reactions such as dermatitis, agranulocytosis,

or hepatitis is higher for mephenytoin than for phenytoin.

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 2. CARBAMAZEPINE

• Primary drug for the treatment of partial & tonic-clonic seizures.

• Related chemically to TCAs

• It is a derivative of iminostilbene with a carbamyl group at the

5 position; this moiety is essential for potent anti-seizure activity

• It is tricyclic compound effective in treatment of bipolar

depression.

• It was initially marketed for the treatment of trigeminal neuralgia

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 Mechanism of Action.

Like phenytoin, blocks Na+ channels at therapeutic concs &

inhibits high-frequency repetitive firing in neurons.

• It also acts presynaptically to decrease synaptic transmission.

NB: carbamazepine has anti-diuretic effects that are sometimes

associated with increased concentrations of ADH in plasma.

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 PK
• Available only in oral form

• almost complete absorption apparently occurs in all patients

• Peak levels are usually achieved 4–8 hours after admin.

• Slowing absorption by giving the drug after meals helps the patient
tolerate larger total daily doses.

• Distribution is slow, and the volume of distribution is roughly 1 L/kg.

• Approximately 75% bound to plasma proteins; no displacement of

other drugs observed.
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 • Rapid tissue distribution
• Concs in the CSF appear to correspond to the conc of free drug
in plasma.
• Has a very low systemic clearance
• Ability to induce CYP2C,CYP3A, and UGT, -decreases OC
levels

• metabolized by Hepatic CYP3A4

• Metabolisedd to several derivatives e.g.( carbamazepine-10,11-

epoxide shown to have anticonvulsant activity).
• 10,11-epoxide is metabolized further to inactive glucuronides
excreted in the urine
• It is inactivated by conjugation and hydroxylation.
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 TOXICITY
• Acute intoxication
- stupor or coma - hyperirritability
-convulsions -respiratory depression.
• During long-term therapy, untoward effects include
-Drowsiness - diplopia and blurred vision
- Vertigo - ataxia
• Other AEs include nausea, vomiting, serious hematological toxicity
(aplastic anemia, agranulocytosis),& hypersensitivity rxns (dangerous
skin rxns, eosinophilia, lymphadenopathy, splenomegaly).
• Late complication - retention of water, with ↓sed osmolality & conc
of Na+ in plasma, especially in elderly patients with cardiac disease
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 OXCARBAZEPINE
• A keto analog of carbamazepine but less potent

• Prodrug- almost immediately converted to its main active metabolite, a

10-monohydroxy derivative

• MOA is similar to that of carbamazepine

• May have better toxicity profile, causes hyponatremia & most AE similar
to those of carbamazepine

• Active metabolite inactivated by glucuronide conjugation & renally

excreted

• Less potent enzyme inducer than carbamazepine

• Half-life of 1–2 hours.

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• No autoinduction

• Substitution of oxcarbazepine for carbamazepine is associated with

↑sed levels of phenytoin & valproic acid coz of reduced induction of
hepatic enzymes.

• Although oxcarbazepine does not appear to reduce the anticoagulant

effect of warfarin, it does induce CYP3A hence ↓se OC levels.

• Approved for monotherapy or adjunct therapy for partial seizures

in adults

• And as monotherapy for partial seizures in children ages 4-16 and

adjunctive therapy in children 2 years of age and older with
epilepsy.
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 ESLICARBAZEPINE
• Eslicarbazepine acetate (ESL)-a prodrug

• used as adjunctive therapy in adults with partial-onset seizures,

with or without secondary generalization.

• It is more rapidly converted to S(+)-licarbazine (eslicarbazine) than

is oxcarbazepine; both have same active metabolite

• MOA is similar to that of carbamazepine, oxcarbazepine.

• Clinically, it is similar to carbamazepine and oxcarbazepine in its

spectrum of action

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• Advantage-has once-daily dosing regimen & t1/2- is 9–11 hours.

• Dosage- 400–1200 mg/d

• Minimal effect when given with carbamazepine, levetiracetam, lamotrigine,

topiramate & valproate.

• Ocs less effective with concomitant ESL administration.

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 3. ANTI-SEIZURE BARBITURATES (PHENOBARBITAL)
• Phenobarbital (LUMINAL, others) was the first effective organic anti-seizure
agent.

• It is a 5-phenyl-5-ethylbarbituric

• Maximal anti-seizure activity is obtained when one substituent at carbon 5

position is a phenyl group.

• Its efficacy, low toxicity, and low cost make it an important agent for these
types of epilepsy.

• its has sedative effects & disturbs behavior in children hence reduced use as
primary agent.

• Not effective for absence seizures.

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Other derivatives of barbituric acid with antiseizure properties.

Mephobarbital

 metharbital

 and primidone.

Mechanism of Action.

Anti-seizure barbiturates act by potentiation of synaptic inhibition

through an action on the GABAA receptor.

They potentiate GABA-induced chloride ion currents by prolonging

periods during which bursts of channel opening occur rather than
increasing
2/10/2020 the frequency of these bursts as seen with BDZs
Ms Loyce 44
• At levels exceeding therapeutic concs, PB also limits sustained
repetitive firing.

• this may underlie some of the anti-seizure effects of higher

concentrations of PB achieved during therapy of status
epilepticus.

Pharmacokinetic Properties.

• Oral absorption is complete but slow

• Peak plasma concs occur several hrs after a single dose.

• 40-60% bound to plasma proteins & in tissues, including brain.

• The therapeutic levels in most patients range from 10 mcg/mL
to 40 mcg/mL.
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• Up to 25% of a dose is eliminated by pH-dependent renal excretion
of the unchanged drug

• Remainder inactivated by microsomal enzymes, mainly CYP2C9,

to less extent byCYP2C19 & CYP2E1.

Toxicity

• Sedation, the most frequent undesired effect in almost all patients

upon initiation of therapy but tolerance develops during chronic
medication.

• Nystagmus and ataxia occur at excessive dosage.

• Irritability and hyperactivity in children

• Agitation and confusion in the elderly

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 Drug Interactions

• Phenobarbital induces UGT enzymes, CYP2C and CYP3A

subfamilies. (decreases conc of drugs metabolized by these
enzymes eg OCS)

• Interaction btn phenytoin & phenobarbital is variable.

• PB plasma conc may be elevated by as much as 40% during co-

admin with valproic acid.

PRIMIDONE( 2-DESOXYPHENOBARBITAL)

• Metabolized by oxidation to phenobarbital &

phenylethylmalonamide (PEMA).

• All three compounds are active anticonvulsants.

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• MOA may be more like that of phenytoin instead of PB

• Dosage- 10–20 mg/kg/d

• Effective against partial seizures and generalized tonic-clonic seizures and

may be more effective than phenobarbital

• Completely absorbed, peak concs abt 3hrs after oral admin.

• Generally distributed in total body water-VD of 0.6 L/kg.

• Not highly bound to plasma proteins; approx ( 70% unbound).

• Both primidone and PB undergo subsequent conjugation & excretion.

• Larger clearance than most other antiseizure drugs (2 L/kg/d)

• Half-life of 6–8 hours.

• Dose-related adverse effects are similar to those of its metabolite (PB)

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 FELBAMATE
• Effective in some patients with partial seizures & proved effective
against the seizures that occur in Lennox-Gastaut syndrome
(pediatric epilepsy syndrome)

• Causes aplastic anemia and severe hepatitis at unexpectedly high

rates and has been relegated to the status of a third-line drug for
refractory cases.

Mechanisms of action (multiple).

• It produces a use-dependent block of the NMDA receptor with

selectivity for the NR1-2B subtype.

• It also produces a barbiturate-like potentiation

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 PK

• Half-life of 20 hrs ( when admin with either phenytoin or carbamazepine)

• Metabolized by hydroxylation & conjugation

• Significant % excreted unchanged in the urine.

• ↑ses plasma phenytoin and valproic acid levels but ↓ses levels of

carbamazepine.

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DRUGS USED IN TREATMENT OF GENERALIZED SEIZURES

SUCCINIMIDES (Ethosuximide ,zarontin, others)

• Is a primary agent for the treatment of absence seizures.

• structure-activity relationship of the succinimides is in accord with that for other anti-
seizure classes

• origin is in the cyclic ureide structure.

Mechanism of Action.

• Ethosuximide reduces low threshold (T-type) Ca2+ currents in thalamic nuerons

• The T-type Ca2+ currents are thought to provide a pacemaker current in thalamic
neurons responsible for generating the rhythmic cortical discharge of an absence
attack.
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 Ethosuximide Pharmacokinetics

• Absorption is complete following oral admin

• Peak levels are observed 3–7 hours after oral administration.

• protein-bound.

• Completely metabolized principally by hydroxylation to inactive metabolites.

• Has a very low total body clearance (0.25 L/kg/d).

• Half-life of approx 40 hrs though values from 18 to 72 hrs have been

reported.

• Can be given in single daily dose, twice-a-day dosage is common.

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TOXICITY: dose-related AE: gastric distress(i.e pain,
nausea, and vomiting-reduce dose

• Others CNS effects: transient lethargy or fatigue and,

headache, dizziness, hiccup, and euphoria-less common

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 VALPROIC ACID & SODIUM VALPROATE

• Anti-seizure properties discovered when it was being used as a vehicle

for other cpds that were screened for this activity

• Valproic acid is fully ionized at body pH hence valproate active form

of the drug

• Valproic acid is one of a series of fatty carboxylic acids that have anti-
seizure activity

• Broad spectrum-treats absence, myoclonic, partial and tonic-clonic

seizures, often preferred to ethosuximide when the patient has

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concomitant generalized tonic-clonic
Ms Loyce
attacks. 54
 VALPROATE
Mechanism of action

• Like phenytoin and CBZ, it blocks sustained high-frequency repetitive firing

of neurons (may give reason for its action ion against partial seizures.

• Valproate also produces small reductions of T-type Ca2+ currents

• Blockade of NMDA receptor-mediated excitation may also be important.

• Valproate facilitate glutamic acid decarboxylase (GAD), the enzyme

responsible for GABA synthesis.

• An inhibitory effect on the GABA transporter GAT-1 observed.

• At very high concs, it inhibits GABA transaminase &succinic semialdehyde

dehydrogenase in the brain, thus blocking degradation of GABA
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 Pharmacokinetic Properties

• Rapidly absorbed and completely after oral admin (80% bioavailabilty).

• Peak plasma conc observed in 1-4 hours(delayed with meals)

• The apparent VD is ~0.2 L/kg.

• Binding to plasma proteins ~90%

• CSF concs suggest equilibration with free drug in the blood but carrier-mediated
transport of valproate both into and out of the CSF.

• 95% of drug undergoes hepatic metabolism(mainly by UGT enzymes and β-

oxidation)

• Less portion metabolized by CYP2C9 and CYP2C19

• < 5% excreted unchanged in urine

• The t1/2 is ~15 hrs but reduced in patients taking other anti-epileptic drugs
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 BENZODIAZEPINES
• Diazepam( iv or rectally)- effective 4 stopping continuous seizure activity,

especially generalized tonic-clonic status epilepticus

• Clobazam is widely used in a variety of seizure types.

• Clonazepam is a long-acting, efficacy against absence seizures

• Clorazepate dipotassium is approved in the USA as an adjunct to TX

complex partial seizures in adults.

• Nitrazepam for infantile spasms & myoclonic seizures (not in USA)

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 MOA
• Act at subsets of GABAA receptors and increase the frequency, but
not duration, of openings at GABA-activated Cl– channels.
• Can reduce sustained high-frequency firing of neurons
PK
• well absorbed after oral administration except clorazepate
• All have high lipid-water solubility
• peak plasma conc-1-4 hours.
• Diazepam is rapidly redistributed especially
• Highly plasma bound
• Cross placental barrier and secreted in breast milk
• Metabolized by CYP3A4 & 2C19
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SUMMARY OF ANTI-CONVUSANTS

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Alternative methods for
treatment of epilepsy:
• Neurosurgery +
• laser therapy

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Other agents
Acetazolamide

• prototype for the carbonic anhydrase inhibitors,

• sometimes effective against absence seizures

• usefulness is limited by the rapid development of tolerance

• Adverse effects are minimal when it is used in moderate dosage for limited periods

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 Status epilepticus
Characterized by prolonged or recurrent seizures without a return to baseline.

CNS infections are a common cause of pediatric status epilepticus

The 2015 International League Against Epilepsy defines status epilepticus as

―a condition resulting either from the failure of the mechanisms responsible for
seizure termination or from the initiation of mechanisms which lead to
abnormally prolonged seizures (after time point t1).

Time points were defined depending on whether the seizure was generalized
tonic-clonic status epilepticus, focal status epilepticus with impaired
consciousness, or absence status epilepticus
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• It is a condition that can have long-term consequences (after time point t2),
including neuronal death, neuronal injury, and alteration of neuronal
networks, depending on the type and duration of seizures‖

• The goal of treatment is rapid termination of behavioral and electrical seizure

activity

• the longer the episode of status epilepticus goes untreated, the more difficult
it is to control and the greater the risk of permanent brain damage.

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Management includes
-prompt admin of appropriately selected anti-seizure medication
-Identification & mgt of any seizure precipitant(s)
-identification & mgt of associated systemic complications

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 Management of status epilepticus
• In the initial therapy phase

A benzodiazepine (specifically IM midazolam, IV lorazepam,

or IV diazepam) is recommended

• In the second phase

options include IV fosphenytoin, valproic acid, or

levetiracetam.

If none of these is available, IV phenobarbital is a reasonable

alternative.
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 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 6–12 months).
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 MAIN INDICATIONS OF ANTIEPILEPTIC DRUGS

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 Anticonvulsive drugs of choice
Grand mal: I choice – valproate or Lamotrigine
Alternative – Carbamazepine, Topiramate or Phenytoin

Petit mal: I choice – Ehosuximide or valproate

Alternative – Clonazepam or Lamotrigine
Partial seizures: I choice – Carbamazepine or
valproate
Alternative – Phenytoin, Lamotrigine, Vigabatrin, Topiramate

Status epilepticus: I choice – Diazepam or Lorazepam (i.v.)

Alternative – Phenobarbital (i.m./i/v.)
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 Treatment of status epilepticus in adults

Patient in opisthotonus (grand mal)

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 GENERAL GUIDE TO ANTIEPILEPSY PHARMACOTHERAPY

(1) The decision whether or not to initiate drug therapy after a

single seizure remains controversial since approximately 25%
of patients may not have another seizure.
(2) Therapy should start with a single drug (70% of patients can
be controlled on one drug (monotherapy).
(3) Anticonvulsant drug therapy should be appropriate to the type
of seizure.
(4) The choice of drugs is also determined by the patient’s age
and sex.
(5) If the attempt to control epilepsy by use of a single drug is
unsuccessful, it should be withdrawn and replaced by a second
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line drug, though these are effective
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in only 10% of patients. 75
 There is little evidence that 2 or 3 drugs are better than one,
but more drugs often mean more ARs.
(6) Effective therapy must never be stopped suddenly,
only gradually.
(7) After a period of at least 2–3 years free from seizures, with-
drawal of anticonvulsants can be considered. In general, dis-
continuing the antiepileptic drug therapy is associated with
about 20% relapse during withdrawal and a further 20% relapse
over the following 5 years. It is recommended that the antiepi-
leptic drug be withdrawn over a period of 6 months. If a fit
occurs during this time, full therapy must begin again until the
patient has been free from seizure for a further 2–3 years.
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