Antiepileptic Drugs Flashcards
Epilepsy Pathophysiology
Causes:
50% idiopathic & 50% caused by a) genetic disorder – runs in the family
b) head trauma
c) brain conditions- brain tumours & stroke are leading cause of adult epilepsy d) infectious diseases- AIDS, meningitis & viral encephalitis
e) prenatal injury
Age – children & older adults more likely Family history
Stroke & vascular disease Dementia→risk in adults
Complications:
Falling & drowning -Car accidents ➤Pregnancy complications Emotional health issues
Absence seizure pathophysiology
● Most often they affect children.
● They can be caused by hyperventilation.
● “Safer” in terms of neurological complications.
● Treatment with inhibition of calcium channels T.
● Considered as petit mal seizures.
● Ethosuxymide and valproate.
Newly Diagnosed Focal
Monotherapy: 1st line agents
Carbamazepine Gabapentin Lamotrigine Levetiracetam Valproic Oxcarbazepine
Newly Diagnosed Focal
Polytherapy: 1st line + 2nd line
Topirmate, Phenobarbital, Phenytoin
Newly Diagnosed Focal
Polytherapy: 1st line + 3rd line
Vigabatrin, tiagabine, lacosamide, Pregablin, Zonisamide
Newly Diagnosed Generalised tonic-clonic
1st line agents
Valproic Acid, Lamotrigin, Levetiracetam
Carbamazepine or oxcarbazepine may ↑ number of myoclonic events
Newly Diagnosed Generalised tonic-clonic
1st line + 2nd line
Topiramate, Zonisamide, Clobazam
As a medical professional what is the course of action of a patient with juvenile epilepsy and a myoclonic attack ?
AVOID Carbamazepine, Oxcarbazepine, Pregablin, Gabadentin, Phenytoin, Vigabatrin, Tiagabine if patients has JUVENILE EPILEPSY + MYOCLONIC ATTACK (use barbiturates instead)
De novo Diagnosed
Generalised Myoclonic
Monotherapy: 1st line agents
Valproic Acids
De novo Diagnosed Generalised Myoclonic
1st Line + 2nd line
Lamotrigin, Levetiracetam
De novo Diagnosed Generalised Myoclonic
1st line + 2rd line
Clonazepam, Zonisamide, Piracetiam
De novo Diagnosed Generalised Atonic and Tonic
1st line agents
Valproic Acids
De novo Diagnosed Generalised Atonic and Tonic
1st Line + 2nd line
Lamotrigine
De novo Diagnosed Generalised Atonic and Tonic
1st line + 2rd line
Topiramate
WHAT IS USED IN DRUG RESISTANT EPILEPSY?
EPIDIOLEX (cannabidiol)
WHAT IS USED IN STATUS EPILEPTICUS
Benzodiazepines
Broad spectrum vs narrow spectrum
● Both focal and generalised seizures- broad spectrum
● Partial or absence seizures - narrow spectrum
Idiosyncrasy
In modern medicine, the term idiosyncrasy refers to the state of increased reactiveness of the body to a specific chemical compound. This quantitatively different reaction to the drug, associated with individual sensitivity, is due to abnormalities of the drug metabolism in the body.
Pregnancy and epilepsy
● Monotherapy with lowest effective dose.
● Valproate therapies are not recommended. (The safest seem to be levetiracetam and
lamotrigine.)
Benzodiazepines Antidote
flumazenil
Benzodiazepines EXAMPLES
Diazepam (long lasting)
Lorazepam (short lasting)
Clonazepam
Diazepam (long lasting)
● available for rectal administration to avoid or interrupt prolonged generalized tonic–clonic seizures or clusters when oral administration is not possible
clonazepam
● may be prescribed as adjunctive therapy for particular types of seizures
Benzodiazepines
MOA:
● Benzodiazepines bind to GABA inhibitory receptors to reduce the firing rate.
● Enhance GABA receptor responses
Benzodiazepines
USES
● Status epilepticus (Diazepam, Lorazepam)
● Absence and myoclonic seizures (clonazepam)
● Infantile spasms (clonazepam)
Benzodiazepines
SIDE EFFECT
● Sedation
What type of drug is carbamazepine?
A Tricyclic
Carbamazepine
MOA
● blocks sodium channels, thereby possibly inhibiting the generation of repetitive action potentials in the epileptic focus and preventing spread.
● Decreases glutamate release
Carbamazepine
USES
● treatment of focal seizures ● generalized tonic–clonic seizures ● trigeminal neuralgia ● bipolar disorder ● Partial seizures
Carbamazepine
Side Effects
● Hyponatremia ● Ataxia ● Diplopia ● Headache ● Nausea ● Weight gain
Carbamazepine
Contraindication:
● absence seizures (because it may cause an increase in seizures)
What type of drug is phenytoin?
A Cyclic ureides
Phenytoin
MOA
● Blocks voltage gated Na channels
● blocks voltage-gated sodium channels by selectively binding to the channel in the
inactive state and slowing its rate of recovery
Phenytoin
USES
Generalised tonic-clonic and partial seizures
Phenytoin
SIDE EFFECTS
● Ataxia ● Diplopia ● Gingival hyperplasia ● Hirsutism ● Neuropathy
What type of drug is Phenobarbital
Cyclic ureides
Phenobarbital
MOA
Enhances GABA receptor responses
Phenobarbital
Therapeutic uses
Generalised tonic-clonic and partial seizures
Phenobarbital
SIDE EFFECTS
● Ataxia
● Sedation
What type of drug is Ethosuximide:
cyclic ureide.
Ethosuximide MOA
● Decreases calcium ion current (t-type)
● reduces propagation of abnormal electrical activity in the brain, most likely by inhibiting
T-type calcium channels
Ethosuximide USES
● Absence seizures
Ethosuximide: SIDE EFFECTS
● GI distress
● Dizziness
● Headache
What is Gabapentin:
● analog of GABA
Gabapentin: MOA
● Blocks calcium ion channels
● gabapentin binds to the α2δ(alpha 2 delta) subunit of voltage-gated calcium channels
● Blocks gaba-t
Gabapentin: USES
● Generalised tonic-clonic and partial seizures
● adjunct therapy for focal seizures
● treatment of postherpetic neuralgia
● good choice for the older patient (there are few drug interactions)
Gabapentin: SIDE EFFECTS
● Ataxia
● Dizziness
● Somnolence
● Weight gain
Gabapentin: CONTRAINDICATIONS
● Renal patients
What type of drug is Pregabalin
GABA DERVIVATIVE
Pregabalin
MOA
● Blocks calcium ion channels
● gabapentin binds to the α2δ(alpha 2 delta) subunit of voltage-gated calcium channels
● inhibiting excitatory neurotransmitter release
Pregabalin
USES
● Partial seizures
● diabetic peripheral neuropathy
● postherpetic neuralgia
● fibromyalgia
Pregabalin: SIDE EFECTS
● Ataxia
● Dizziness
● Somnolence
● Weight gain
Pregabalin: CONTRAINDICATION
● Renal dysfunction
Pregabalin: CONTRAINDICATION
● Renal dysfunction
Vigabatrin
MOA
● irreversible inhibitor of GABA-Transaminase
Vigabatrin
USE
● Partial seizures
Vigabatrin: SIDE EFFECTS
● Drowsiness
● Dizziness
● Psychosis
● Ocular effects
Lacosamide
MOA:
● Blocks Na channels
● resulting in stabilization of hyperexcitable neuronal membranes and inhibition of
repetitive neuronal firing
Lacosamide
Therapeutic uses:
● Focal seizures
● Generalised seizures
Lacosamide
Adverse effects:
● Dizziness ● Headache ● Diplopia
● Fatigue
Lamotrigine
MOA
● Blocks sodium and calcium channels
● Decreases neuronal glutamate release
Lamotrigine
Therapeutic uses:
● Generalised tonic-clonic seizures ● Partial seizures ● Myoclonic seizures ● Absence seizures ● Lennox-Gastaut syndrome ● bipolar disorder ● Preganacy
Lamotrigine
Adverse effects:
● Dizziness ● Headache ● Diplopia
● Rash
Levetiracetam
MOA:
● Binds to synaptic protein SV2A
● Modifies gaba and glutamate release
● Blocks calcium channels
Levetiracetam
Therapeutic uses:
● Generalised tonic-clonic seizures ● Partial seizures ● Focal-onset seizures, ● Myoclonic seizures ● Pregnancy
Levetiracetam
Adverse effects:
● Dizziness ● Nervousness ● Depression ● Seizures ● mood alterations ● Psychomotor anxiety
Perampanel
MOA:
● Blocks glutamate AMPA receptors
Perampanel
● Focal seizures
● Generalised tonic-clonic seizures
Perampanel
Adverse effects:
● Dizziness ● Headache ● Somnolence ● Behavioral changes ● serious psychiatric ● behavioral reactions ● Aggression ● Hostility ● Irritability ● Anger ● homicidal ideation.
Rufinamide
MOA:
● Blocks Na channels
Rufinamide
Therapeutic uses:
● Lennox-gastaut syndrome
● Focal seizures
Rufinamide
Adverse effects:
● Somnolence
● Diarrhea
● Fever
● shortened QT intervals
Rufinamide
CONTRAINDICATIONS
Familial shortened QT interval
Tiagabine
MOA:
● Blocks GABA reuptake
● blocks GABA uptake into presynaptic neurons permitting more GABA to be available for
receptor binding and thereby enhancing inhibitory activity
Tiagabine
Therapeutic uses
● Partial seizures
● focal seizures
Tiagabine
Adverse effects:
● Dizziness
● Nervousness
● Depression
● Seizures
Tiagabine
CONTRAINDICATIONS
● should not be used for indications other than epilepsy
Topiramate
MOA:
● Increase GABA effect
● blocks voltage-dependent sodium channels
● reduces high-voltage calcium currents (L type)
● carbonic anhydrase inhibitor
Topiramate
Therapeutic uses:
● Generalised tonic-clonic seizures ● Absence seizures ● Partial seizures ● Migraine ● focal and primary generalized epilepsy
Topiramate
Adverse effects:
● Sleepiness ● Cognitive slowing ● Confusion ● Paresthesias ● weight loss ● Renal stones ● Glaucoma ● oligohidrosis (decreased sweating) ● Hyperthermia ● Articulation disorder ● Anorexia nervosa
Valproate
MOA:
● Blocks high frequency firing
● Blocks Na channels
Valproate
Therapeutic uses:
● Generalised tonic-clonic seizures
● Partial seizures
● Myoclonic seizures
Valproate
Adverse effects:
● Nausea
● Alopecia
● Weight gain
● Teratogenic
Valproate CONTRAINDICATION
● Pregnancy
Zonisamide
MOA:
● Blocks sodium channels and T-type calcium currents
Zonisamide
USES
● Generalised tonic-clonic seizures
● Partial seizures
● Myoclonic seizures
● focal epilepsy
Zonisamide
Adverse effects:
● Sleepiness ● Cognitive slowing ● Poor concentration ● Paresthesias ● kidney stones ● Oligohidrosis
Zonisamide
CONTRAINDICATION
sulfonamide or carbonic anhydrase inhibitor hypersensitivity
Retigabine
● It affects the opening of potassium channels.
● Recommended as an additional drug.
● Low antiepileptic potential.
Retigabine
MOA
● Activates potassium channels
Retigabine
Therapeutic uses:
● Focal seizures
Retigabine
Adverse effects:
● Dizziness
● Somnolence
● Retinal changes
Felbamate
● It probably reacts with NMDA.
● Used to treat Lennox-Gastaut type of childhood epilepsy.
● Transaminases monitoring.
