Epilepsy Flashcards
What is epilepsy?
A chronic disorder characterized by recurrent seizures
What is a seizure?
A short term episode of abnormal firing of cerebral neurons
Partial or generalized
What can cause seizures?
Fever, head injury, tumor, hereditary, alcohol withdrawal and metabolic disorder
What is a partial (focal) seizure?
Initiated in neurons in a localized area of one cerebral hemisphere
Simple, complex, secondary generalization
What is a simple partial seizure?
No loss of conciousness
Preceeded by an aura sometimes
What is complex partial seizure?
Impaired consciousness often with automatisms
What is a secondary generalized partial seizure?
Seizures that spread to activate both hemispheres
Part of body begins to tingle then jerk, then jerking spreads throughout body
What is a generalized seizure?
Simultaneous activation of both cerebral hemispheres
Tonic-clonic, absence
What is a tonic-clonic generalized seizure?
Loss of consciousness, extension then jerking of the body with stiffness finishing by passing out into a deep sleep
What is an absence generalized seizure?
Impaired consciousness sometimes with automatisms
Blanking out for a few seconds, blinking
What does a normal EEG look like?
Activity mostly in the left and right occipital lobes
What does the EEG of a partial seizure look like?
More activity in one side of the brain (left frontal and temporal)
What does the EEG of a complex partial seizure look like?
Similar to that of a simple partial seizure
What does the EEG of a generalized tonic-clonic seizure look like?
All parts of the brain show large spikes (close together then more spread apart throughout) in activity.
What does the EEG of a generalized absence seizure look like?
Very similar large, organized spikes throughout entire brain
What are the 4 mechanisms of action of anti-epileptic drugs?
Block voltage-dependent sodium channels (decreases neuronal firing) Inhibit excitatory (glutamate) transmission Increase inhibitory (GABA) transmission Block voltage-activated Ca channels (stops depolarization)
How does depolarization and hyperpolarization affect a Na cell?
Depolarization enhances channel opening (Gate A)
Hyperpolarization blocks channel opening
Channel then becomes inactive (Gate B closes)
Where do many anti-epileptic drugs work on the Na channel?
Prevent the conversion of the inactive channel to closed channel (From closed gate B to gate A)
What drugs are used to treat partial seizures?
Carbamazepine, phenytoin or valproate
What drugs are used to treat generalized tonic-clonic seizures?
Carbamazepine, phenytoin or valproate
What drugs are used to treat generalized absence seizures?
Ethosuximide
What drugs are used to treat generalized tonic-clonic and absence seizures?
Valproate
What drugs are used to treat atypical generalized seizures?
Valproate
What can be added to drug therapy of partial seizures?
Lamotrigine, gabapentin or topiramate
How does carbamazepine work?
Inhibits voltage-gated sodium channels and induces it’s own metabolism
Dose adjustments are required
What are the drug interactions with carbamazepine?
Can enhance the metabolism of many other antiepileptics including phenytoin and valproate toxicity
What are the adverse effects of carbamzepine?
Double vision, ataxia (poor balance, uncoordination), nausea
High doses: drowsiness
Skin rash and leukopenia (low white blood cells)
How does phenytoin work?
Blocks voltage-gated sodium channels
Absorption differs among formulations
Dramatic increases in plasma levels with small increases in dose
What are the drug interactions with phenytoin?
Highly bound to plasma proteins
Induces CYP 3A4 and thus the metabolism of carbamazepine, valproate, vitamin K and contraceptives
What is the metabolism of phenytoin enhanced by?
Phenobarbital and carbamazepine, requires dose adjustment
What are the adverse effects of phenytoin?
Double vision, ataxia, gingival hyperplasia, hirsutism (hair growth), mild peripheral neuropathy, megaloblastic anemia, osteomalacia
How does phenobarbital and primidone work?
Enhance the inhibitory effects of GABA
Primidone is metabolized to phenobarbital
Induces it’s own metabolism
What are the drug interactions with phenobarbital and primidone?
Induces liver microsomal enzymes so drug interactions are common with vitamin K and oral contraceptives
What are the adverse effects of phenobarbital and primidone?
Drowsiness, ataxia, respiratory depression and decreased motor skills
Skin rash, dependence
How does gabapentin work?
Increases the release of GABA and decrease the metabolism of GABA
Not metabolized, doesn’t induce hepatic enzymes
Adjunctive therapy
What are the adverse effects of gabapentin?
Sedation, dizziness, headache, tremor, ataxia, nausea, constipation
Will resolve in 2 weeks
How does topiramate work?
Inhibits voltage gated Na channels, increases GABA, inhibits glutamate
Adjunctive therapy or mono in partial and tonic-clonic
What are the adverse effects of topiramate?
Fatigue, dizziness, mental slowing and nausea
How does lamotrigine work?
Blocks voltage gated sodium channels
Adjunctive therapy or mono for partial and absence
What are the adverse effects of lamotrigine?
Dizziness, headache, skin rashes
How does ethosuximide work?
Blocks voltage activated calcium channels
What are the adverse effects of ethosuximide?
Stomach aches and vomiting (tolerance will develop)
Rash, may increase tonic-clonic seizures
How does clonazepam work?
Enhances the inhibitory effects of GABA
What are the adverse effects of clonazepam?
Sedation and tolerance to anti-seizure effects
How does valproate work?
Voltage gated sodium and calcium channels, enhances inhibitory effects of GABA
What are the drug interactions with valproate?
Inhibits metabolism of other drugs including antiepileptics
What are the adverse effects of valproate?
Nausea, vomiting (initiate therapy slowly)
Tremor at high concentrations
Spina bifida in babies if taken while pregnant
What are the other uses of anti-epileptic drugs?
Bipolar disorder (carbamazepine, valproate), anxiety disorders, alcohol abuse, spasticity, migraine, cluster headache, neuropathic pain (gabapentin)
What drugs are used in the case of status epilepticus?
IV diazepam or lorazepam are used to stop the seizures and phenytoin may be initiated for longer term control
have to gradually increase antiepilieptics
What must be monitored while on antiepileptics?
Blood level monitoring to maintain therapeutic levels, especially for drugs that can affect drug metabolizing enzymes
What should be done about seizures in pregnancy?
Uncontrolled seizures are a greater risk to the fetus than the drugs
Lowest effect dose should be used, one drug at a time (dose may need to be increased due to increased metabolism-monitor blood levels at least once a month)
