Anti-epileptics Flashcards
Epilepsy
Chronic disorder of recurrent seizures
Seizures
Finite episodes of brain dysfunction resulting from abnormal discharge of cerebral neurons
Classification of Seizures
- Partial seizures
- Simple partial seizures
- Complex partial seizures
- Partial w/ secondary generalized tonic-clonic seizures - Generalized seizures
- Tonic-clonic seizures
- Absence seizures
Simple partial seizures
- NO loss of consciousness
- Abnormal activity of 1 limb or muscle group
Complex partial
- Loss of consciousness
- Motor dysfunction- chewing, movements, diarrhea & urination
Partial w. Secondary Generalized Tonic-Clonic Seizure
Partial seizure –> Tonic-clonic seizure
- Loss of consciousness
Generalized
- IMMEDIATE loss of consciousness
- Convulsive or non-convulsive
Generalized Tonic-clonic
Absent seizures (Petit mal)
- Brief & abrupt self-limiting loss of consciousness
- Stares & has rapid eye-blinking
- Usually children
- 3Hz spike & wave pattern emerges abruptly & ceases after a few seconds on EEG
Other Generalized seizures
- Atonic
- Tonic
- Clonic
- Myoclonic
- Febrile
- Status epilepticus
Mechanism of seizures
Dec inhibitory synaptic activity (GABA) OR Inc excitatory activity (Glutamate)
- GABAa antagonist & Glutamate agonist triggers seizures
- Glutamate receptor antagonists & drugs that enhance GABAergic transmission inhibits seizure
MOA of Antiepileptic drugs
- Block Voltage-gated Ion Channels
- Na+ channels
- T-type Ca2+ channels - Modulate Synaptic Transmission
Drugs that block Na+ channels
- Phenytoin
- Carbamazepine
- Lamotrigine
- Zonisamide
- Oxcarbazepine
(May contribute to the effects of Phenobarbital, Valproate & Topiramate)
Drugs that block T-type Ca2+ channels
- Ethosuximide
- Valproate
Used for absent seizures (oscillatory neuronal activity between thalamus & cortex)
Drugs that enhance GABAergic transmission post-synaptically
- Benzos
- Barbiturates
- Topiramate
Direct action on GABA receptors
Drugs that enhance GABAergic transmission pre-synaptically
- Tiagabine - Inhibits GABA reuptake
2. Vigabatrin - Inhibits GABA aminotransferase
Drugs that Reduce Glutamatergic Neurotransmission Post-synaptically
- Phenobarbital
- Topiramate
Blocks Glutamate receptors
Drugs that Reduce Glutamatergic Neurotransmission Pre-synaptically
- Gabapentin
- Pregabalin
Dec Glutamate release by blocking presynaptic voltage-gated Ca2+ channels - Levetiracetam
Binds to Synaptic Vesicle Glycoprotein 2A (SV2A) –> Release of Glutamate & GABA
Tonic-clonic seizure management
- Carbamazepine
- Oxcarbazepine
- Valproate
- Lamotrigine
- Phenytoin
- Topiramate
Absent seizure management
Ethosuximide & Valproate (DOC)
- If tonic-clonic is present use Valproate as DOC
- Atypical absent seizure - Valproate
Lamotrigine also effective
Myoclonic seizure management
Valproate (DOC)
Topiramate
Levetiracetam - Adjunctive therapy
Atonic seizure management
Refractory to all drugs
- Valproate & Lamotrigine may be effective
Febrile Convulsions management
Seizure <15 minutes = Supportive treatment
Seizure > 15 minutes = Diazepam (IV or Rectal)
Status Epilepticus
- Single seizure lasting >5 minutes
OR - 2 or more seizures w/o recovery of consciousness
- Convulsive or non-convulsive
- Usually generalized tonic-clonic seizures
Status Epilepticus Management
Initial therapy 5-20 mins
- Midazolam (IM) OR Lorazepam OR Diazepam (IV)
Second therapy 20-40 mins
- (IV) Fosphenytoin OR Valproic acid OR Levetiracetam
- 2nd line = IV Phenobarbital
Third therapy 40+ mins
- Repeat 2nd therapy OR
- IV Thiopental, Midazolam, Phenobarbital OR Propofol
Drug-induced seizure management in non-epileptics pts
- Diazepam
- Lorazepam
- Phenobarbital
Drugs that induce Cytochrome P450
- Carbamazepine
- Phenobarbital
- Phenytoin
- Oxcarbazepine (weak)
Adverse effects of valproate
- Hepatotoxicity
NB: It inhibits Cytochrome P450, metabolism of other drugs and itself
Adverse effects of Phenytoin
- Diplopia & ataxia
- Gingival hyperplasia
- Coarsening of facial features in children
- Hirsutism
- Rash (SJS)
NOT given to children due to AE
NB: Zero order kinetics of elimination
Adverse effects of Carbamazepine
- Aplastic anemia
- Agranulocytosis
- Rash (SJS)
Stevens- Johnson Syndrome & Toxic Epidermal Necrolysis (SJS/TEN)
- Phenytoin, Lamotrigine & Carbamazepine
Discontinues at the 1st sign of rash when using Lamotrigine & Carbamazepine because of Black box warnings
Adverse effects of Phenobarbital
- Sedation & drowsiness
- Tolerance & Dependence
- Cognitive impairment
- Hyperactivity
- Rash (SJS)
P450 inducer
Adverse effects of Primidone
Similar to its metabolite (phenobarbital)
- Sedation & drowsiness
- Tolerance & Dependence
- Cognitive impairment
- Hyperactivity
- Rash (SJS)
P450 inducer
Adverse effects of Vigabatrin
Visual field loss
Adverse effects of Felbamate
- Aplastic anemia
- Hepatotoxicity
USED for refractory epilepsy
Discontinuation of Anti-epileptic therapy
- 3-5 years seizure free
Discontinuation should be slow and withdrawn gradually to avoid withdrawal seizures.
If the pt. is on combination therapy, withdraw drugs one at a time
Overdose
Rarely lethal
- Barbiturates may cause Resp. depression
- Treatment is supportive
Do NOT use Stimulants
Which drugs is Teratogenic
Valproate most risk of congenital malformation in infants
NB: Folic acid dec. incidence of Neural tube defects but does not prevent it
Newborn Hemorrhagic Disease
Enzyme-inducing drugs that inc. Vit. K degradation in fetus –> Bleeding in fetus
Vit. K supplement is recommended for mother in the final month of pregnancy
Other uses Of Anti-epileptic drugs
- Carbamazepine = Neuropathic pain & bipolar
- Gabapentin = Neuropathic pain
- Lamotrigine = Bipolar Disorder
- Pregabalin = Neuropathic pain
- Topiramate = Migraine
- Valproate = Bipolar disorder & Migraine
- Primidone = DOC for essential tremor along with Propranolol
Non-pharmacologic approaches to Epilepsy
- Surgery- resection of local area of brain
- Ketogenic diet - 4:1:1 fat: protein: carbohydrate
- Vagus nerve stimulation - stimulation of left vagus with implanted pace-maker-like device
