Lecture 9 - Epilepsy Flashcards
What is epilepsy?
Chronic disease characterized by recurrent seizures
What is a seizure?
Sudden, brief disruption of normal neuron functioning
What are some causes of epilepsy?
- Stroke
- Brain tumour
- Brain infection
- Past head injury
- Metabolic problems
- Genetic factors
- Other neurological conditions
What are some causes of seizures?
- High fever, especially in infants
- Drug use, alcohol withdrawal
- Near-drowning or lack of O2
- Metabolic disturbances
- Head trauma
- Brain tumour or infection, stroke
- Complication of diabetes or pregnancy
What is a partial seizure?
Initiated in neurons in a localized area of one cerebral hemisphere
What are the 3 types of partial seizures?
1) Simple - no loss of consciousness
2) Complex - impaired consciousness often w/ automatisms
3) Secondary generalized - seizure spreads to activate both hemispheres
What is a generalized seizure?
Simultaneous activation of both cerebral hemispheres
What are the 2 types of generalized seizures?
1) Tonic-clonic - loss of consciousness, extension then jerking of body
2) Absence - impaired consciousness, sometimes w/ automatisms
What typically precedes a seizure?
Aura
What is an electroencephalogram?
Record of electrical activity of brain by placing electrodes on scalp
What will the EEG of a partial seizure look like?
Abnormal activity in left frontal and left temporal lobes
What will the EEG of a tonic-clonic seizure look like?
Abnormal activity in all brain regions
What will the EEG of a generalized absence seizure look like?
Abnormal slow wave electricity activity in all brain regions
What is a common symptom of complex partial seizures?
“Picking lint”
What are the symptoms of a partial seizure w/ secondary generalization?
- Begins w/ jerking which spreads and patient passes out
- Whole body starts to jerk
What are the symptoms of a tonic-clonic seizure?
- Muscle jerking, whole body is involved
- Lasts 1-3 minutes; afterwards px may be confused, have a headache, and want to sleep
What are symptoms of a generalized absence seizure?
- Typically in children
- Absence of aura
- Loss or impairment of consciousness (“blanks out”)
- 5-15 second lapses of consciousness, sometimes mistaken for daydreaming
What do anti-epileptic drugs do?
- Decrease frequency and/or severity of seizures in pxs w/ epilepsy
- Treats symptoms, not underlying cause
What is the goal of therapy for epilepsy?
Maximize quality of life by eliminating seizures or diminishing seizure frequency while minimizing adverse drug effects
What are mechanisms of action for AEDs?
- Use dependent blockade of voltage gated Na channels (decrease rate of Na channel opening)
- Inhibit excitatory (glutamate) neurotransmission
- Increase inhibitory (GABA) neurotransmission
- Block voltage gated Ca channels
What is the difference btwn normal neurons and neurons that are susceptible to seizure activity?
- Normal neurons have a balance of excitation and inhibition
- Neurons susceptible to seizure activity show increased excitation or decreased inhibition
Which drugs can be used to treat all types of partial seizures?
- Carbamazepine
- Phenytoin
- Valproate
Which drugs can be used to treat tonic-clonic seizures?
- Carbamazepine
- Phenytoin
- Valproate
Which drug can be used to treat generalized absence seizures?
Ethosuximide
Which drugs can be used to treat generalized tonic-clonic and absence, or atypical generalized seizures?
Valproate
What does carbamazepine do?
Inhibits voltage-gated Na+ channels
Carbamazepine can enhance the effects of ____
Other AEDs including phenytoin and valproate
What are some dose related adverse effects of carbamazepine?
Double vision and ataxia
What does phenytoin do?
Blocks voltage-gated Na channels
Metabolism of phenytoin is ____ dependent
Dose
What does phenytoin induce?
CYP 3A4, thus increases metabolism of many drugs
What enhances the metabolism of phenytoin?
Phenobarbital and carbamazepine
Which side effects of phenytoin require a dosage adjustment?
Double vision and ataxia
What do phenobarbital and primidone do?
Enhance inhibitory effects of GABA
What metabolizes primidone?
Phenobarbital
What are some dose related side effects of phenobarbital and primidone?
- Drowsiness
- Ataxia
- Respiratory depression
- Decreased motor skills
What does gabapentin do?
Increases release of GABA from neurons (appears to decrease GABA metabolism)
When is topiramate used?
Approved for adjunctive therapy, also appears beneficial for monotherapy in partial and tonic-clonic seizures
What does topiramate do?
Inhibits voltage sensitive Na channels, increases GABA effects, and inhibits glutamate receptors
What affects the metabolism of topiramate?
Other AEDs
When is lamotrigine used?
- Adjunctive therapy
- Also appears effective for monotherapy for partial and absence seizures
What does lamotrigine do?
Blocks voltage-gated Na channels
What affects the metabolism of lamotrigine?
Other AEDs
What does ethosuximide do?
Blocks voltage activated Ca channels
What is an important adverse effect of ethosuximide?
May increase tonic-clonic seizures
When is clonazepam used?
Generalized absence seizures
What does clonazepam do?
Enhances inhibitory effects of GABA
When is valproate used?
Generalized tonic-clonic, absence, or mixed seizures
What does valproate do?
Inhibits voltage-gated Na and Ca channels and enhances GABA
What does valproate inhibit
Metabolism of other drugs, including AEDs
Is valproate safe in pregnancy?
No, risk of spina bifida
What are some other uses of AEDs?
- Bipolar disorder (carbamazepine and valproate)
- Anxiety disorders
- Alcohol abuse
- Spasticity
- Migraine, cluster headaches
- Neuropathic pain (especially gabapentin)
What is used to stop status epilepticus?
IV diazepam or lorazepam (lorazepam is preferred)
Why are AEDs gradually increased to therapeutic concentrations and withdrawn gradually?
To decrease risk of adverse effects; to decrease risk of inducing seizure
