Download EPILEPSY

ANTICONVULSANTS
SAMUEL AGUAZIM (MD)
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What is a Epilepsy?
• Epilepsy is a chronic disorder characterized by
recurrent episodes in which the brain is subject to
abnormal excessive discharges (seizures) synchronized
throughout a population of neurons.
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EPILEPSY
PRIMARY or IDIOPATHIC
SECONDARY
KNOWN CAUSES:
• HEAD INJURY
• TUMORS
• MENINGITIS
• HYPOGLYCEMIA
• DRUG WITH DRAWAL
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The two main categories of seizures include
Partial seizures – no loss of consciousness
and
Generalized seizures – loss of consciousness
• A partial seizure can evolve to a generalized seizure.
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• Partial Seizures
The site of origin is a localized or discreet area in one hemisphere of the brain.
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Symptoms depend on the site of neuronal discharge
The two most common types of partial seizure are
Simple partial and
Complex partial.
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Simple Partial
• These produce symptoms associated with the area of abnormal
neural activity in the brain confined to single locus:
• The electrical discharge does not spread
• Can occur at any age
• motor signs, sensory symptoms, autonomic signs and symptoms
• There is no impairment of consciousness in simple partial
seizures.
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Complex Partial
• Impairment of consciousness, characteristic of complex
partial seizures (CPS)
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Results in the inability to respond to or carry out simple
commands or to execute willed movement, and a lack of
awareness of one’s surroundings and events.
• Exhibit complex sensory hallucinations, mental
distortion and motor dysfunction
• Experience initial seizures before age of 20 yrs
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Generalized Seizures
• At the onset, seizure activity occurs simultaneously in large areas of
the brain, often in both hemispheres.
• Begin locally and rapidly spread to both the hemispheres.
• Loss of consciousness
• Seizures can be convulsive or non-convulsive.
• The two most common types are tonic-clonic (grand
mal) and Absence (Petit mal).
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• Tonic-clonic (grand mal). Most common
• There is loss of consciousness during the seizure.
• The tonic phase, consisting of increased muscle tone (rigidity), is
followed by The Clonic phase, which involves jerking of the
extremities.
• Followed by confusion and exhaustion.
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• Absence (petit mal) This type occurs most often in
children, usually beginning between the ages of 5 and 12
years and often stopping spontaneously in the teens.
• The loss of consciousness is so brief that the child usually does not
even change position.
• Typically described as a blank stare and often
misinterpreted as daydreaming.
• Most absence seizures last 10 seconds or less.
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• Myoclonic seizures are rapid, brief contractions of bodily
muscles, sudden jerks or clumsiness.
• Infantile Spasms a.k.a West Syndrome sudden spasm or
bending (flexion) of the body either at the waist or neck.
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• Status Epilepticus was defined as 30 minutes of continuous seizure
activity or a series of seizures without return to full consciousness
between the seizures
• Febrile seizures are convulsions brought on by a fever in infants or
small children.
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CLASSIFICATION
Seizures
• PARTIAL / FOCAL
• SIMPLE
• COMPLEX
• GENERALIZED
• GRAND MAL ( tonic clonic)
• PETIT MAL ( Absence)
• MYOCLONIC
• FEBRILE
• STATUS EPILEPTICUS
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ANTIEPILEPTIC DRUGS
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PHENYTOIN
CARBAMAZEPINE
VALPROIC ACID
ETHOSUXIMIDE
BENZODIAZEPINES
BARBITURATES
LAMOTRIGINE - NEWER AGENTS
GABAPENTIN - NEWER AGENTS
TIAGABINE
- NEWER AGENTS
TOPIRAMATE - NEWER AGENTS
VIGABATRIN - NEWER AGENTS
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• BARBITURATES - PHENOBARBITAL
PRIMIDONE
• BENZODAIZEPINES - DIAZEPAM
CLONAZEPAM, CLORAZEPATE
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ANTI EPILEPTIC DRUGS MECH
• INHIBIT ELECTRICAL DISCHARGE
• INHIBIT SPREAD OF DISCHARGE
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PHENYTOIN
MECH:
• DECREASES Na INFLUX
• STABILIZES CELL MEMBRANE
• DECREASES INFLUX OF Ca
• DECREASES FIRING RATE
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ACTION :
• DECREASES PROPAGATION OF ABNORMAL IMPULSES
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USES:
First line treatment for tonic-clonic seizures
First line prophylaxis for status epilepticus
Treatment for simple and complex seizures.
Drug of choice for initial therapy in adults
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DROWSINESS – LITTLE
• HYPNOSIS – NO
KINETICS :
• ROUTE – ORAL, IV – ST. EPILEPTICUS
• MET : LIVER, EASILY SATURATED
• EXCRETION : URINE.
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PHENYTOIN - SE
• Side effects of phenytoin include:
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CNS Depression
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Aplastic anemia
Gingival hyperplasia
Hirsutism
Osteomalacia from decreased vitamin D
Megaloblastic anemia from decreased folate (decreased GI absorption from
inhibition of conjugases)
Stevens-Johnson syndrome
Nystagmus
Yellow-browning of skin
Neuropathy (vertigo, ataxia, headache)
SLE-like syndrome
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TERATOGENIC EFFECT
• FETAL HYDANTOIN SYNDROME
• IF GIVEN IN PREGNANCY
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CLEFT LIP, CLEFT PALATE
GROWTH RETARDATION
LOW IQ
CONGENITAL HEART DISEASES
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Phenytoin's teratogenic effects usually
result in cleft lip and palate.
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CARBAMAZEPINE
• MECH : BLOCKS Na CHANNELS
• USED MAINLY -All partial, grand mal epilepsy
• Drug of choice in Trigeminal neuralgia
• ORAL ROUTE
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SE :
• MC : GIT
Chronic use can cause :
• STUPOR, RESP DEPRESSION, COMA
• APLASTIC ANEMIA, THROMBOCYTOPENIA,
AGRANULOCYTOSIS,
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LIVER FAILURE
Steven-Johnson syndrome
Teratogenicity
Cleft lip and palate
Spina bifida
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Steven-Johnson syndrome
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Carbamazepine's teratogenic effects usually result
in cleft lip, cleft palate, and spina bifida.
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BARBITURATES
• PHENOBARBITAL
• PRIMIDONE
• MECH
• May be due to GABA activation
• USES ; FEBRILE CONVULSIONS, CAN ALSO BE
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USED FOR SIMPLE & GRAND MAL EPILEPSY
Not effective in complex partial
Induced CYP450
SE : SEDATION, ATAXIA, NYSTAGMUS, VERTIGO
CHR: PSYCHOSIS.
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Rebound seizures occur on discontinuance
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PRIMIDONE
Also effective in complex partial
SE
Same as phenobarbital
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BENZODIAZEPINES
• DIAZEPAM, CLONAZEPAM, CLORAZEPATE
• SAFEST DRUGS OF ALL THE
ANTIEPILETPTIC DRUGS
• Diazepam - Slow I. V. – Status Epilepticus
• SE : Resp depression, CVS depression with i.v.
administration of high doses
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• CLONAZEPAM, CLORAZEPATE
• For Chronic treatment
• DIAZEPAM, LORAZEPAM
• For acute conditions Status EPI
• Lorazepam longer duration than diazepam
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VALPROIC ACID(Divalproex)
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MECH : GABA action increased
Blocks Na Channels
Broad spectrum antiepileptic drug
Inhibitor of CYP45O
USES : MYOCLONIC SEIZURES and Bipolar disorder
Absent seizures – 2nd drug of choice. (hepatotoxicity)
SE : hepatotoxicity
• GIT , TREMOR, ATAXIA,SEDATION
• THROMBOCYTOPENIA
• CI : LIVER FAILURE
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ETHOSUXIMIDE ( zarontin)
• Mech: Reduces propagation of abnormal electrical activity in
the brain by inhibiting Calcium channels
• USES: Drug of choice for ABSENCE SEIZURES
SE:
• MC : GIT distress
• CONFUSION,
• LACK OF CONCENTRATION
• STEVEN JOHNSON SYNDROME.( skin reaction)
• Headache,
• Itching
• Fatigue
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Adjunct Antiepileptic drugs
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LAMOTRIGINE ( lamictal)
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Broad spectrum
IHIBITS GLUTAMATE, ASPARTATE
Blocks Na channels and high voltage ca channels
Prevents firing
Can be tonic-clonic, simple partial, complex partial
and absence seizures and Lennox-Gastaut
Syndrome
• SE : RASH, Drowsiness, ataxia, confusion, blood
dyscrasias
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• Lennox-Gastaut syndrome
(LGS), or childhood epileptic
encephalopathy, is a pediatric
epilepsy syndrome characterized
by multiple seizure types;
mental retardation or
regression; and abnormal
findings on
electroencephalography (EEG).
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GABAPENTIN.( neurontin)
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Analogue of GABA
Mech – Not known
May interfere with ca channels
Can be used for Simple and partial seizures, peripheral
neuropathy and Postherpetic neuralgia
SE; Sedation, Ataxia, Drowsiness, ataxia, fatigue
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TIAGABINE
Blocks GABA uptake into presynaptic neurons
More GABA for receptor binding
Exe: BILE ( Major), small amt in Urine
It is effective in decreasing the number of seizures in patients
with partial onset epilepsy.
• SE: Drowsiness, ataxia, tremor,
GI upset dizziness
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TOPIRAMATE
Many actions, Broad spectrum
Blocks Na channels
Increases GABA activity
Block Ca channels
Prevent Phosporylation of proteins
Has shown reduction in seizures in refractory cases
when used with other Anti-epileptic drugs.
• Can be used tonic-clonic, simple and complex
seizures as well as for migraine prophylaxis..
• Exe: Urine
• SE: Drowsiness, ataxia, Nephrolithiasis, taste alteration,
confusion
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VIGABATRIN
• Inhibit enzyme GABA transaminase
• Increases the GABA levels
• Can be used for Partial, General tonic clonic seizures &
sometimes for Infantile spasms
• Exe: Urine
• Adv: very less drug interactions
• SE: Aggression, Alopecia, Skin rash, drowsiness.
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