Epilepsy Flashcards
What is epilepsy?
a chronic disease characterized for recurrent seizures
What is a seizure?
A short term episode of abnormal firing of the cerebral neurons
- seizures are classified as partial or generalized
What are some common causes of seizures?
fever, head injury, heredity, alcohol withdrawal, metabolic disorder
What is a partial (focal) seizure?
initiated by neurons in a localized area of one cerebral hemisphere
- Simple: no loss of consciousness
- complex: impaired consciousness often with automatisms
- secondary generalizedL seizures spread to activate both hemispheres
What is a generalized seizure?
simultaneous activation of both cerebral hemispheres
- Tonic clonic: loss of consciousness, extension then jerking of the body
- Absence seizure: impaired consciousness sometimes with automatisms
- Other types can exist as well
What is the motor homunculus?
- a representation of anatomical structures in the brain
- the larger the representation of the body part on the motor homunculus, the more the brain will stimulate that one area of the body
- this can help to give an idea as to the brain location of the seizure focus when we see one part of the body more activated than another
Partial Seizure
initiated by neurons in a localized area of one cerebral hemisphere
What do electroencephalograph readings tell us about seizures?
- show abnormal electrical activity in specific brain regions during a partial seizure-this is compared to an EEG of a normal brain
Complex partial seizure
initiated in neurons in a localized area of one of the cerebral hemispheres, but spreads very easily
- seizures spread and EEG similar to simple partial seizure
Partial Seizure with Secondary Generalization
- initiated in neurons in a localized area of one cerebral hemisphere, then seizures spread to activate both hemispheres
Generalized tonic-clonic seizure
simultaneous activation of both the cerebral hemispheres
- point of origin is in the thalamus - many of these seizures have a genetic origin
What is considered status epilepticus?
When a seizure lasts for longer than 5-10 minutes
- this is considered a medical emergency
What does an EEG show during a generalized tonic-clonic seizure?
- abnormal electrical activity in all brain regions during a generalized tonic-clonic seizure
What is an absence seizure?
no motor involvement in the upper and lower body- only a twitching of the eyes sometimes
- often goes undiagnosed and is mistaken for the child “packing out”
What does an EEG show in an absence seizure?
shows abnormal slow wave electrical activity in all brain regions
What are the different MOAs for seizure medications?
- use dependent blockade of voltage-dependent Na channels
- reduces the rate of Na channel opening - inhibit excitatory (glutamate) neurotransmission
- decrease glutamate exposure and reduce neuronal firing - increase inhibitory (GABA) neurotransmission
- enhance chloride influx, hyperpolarize neurons and reduce neuronal firing - block voltage activated calcium channels
- neurons in thalamus are dependent on calcium channel pacemaker for depolarization
- depolarization of thalamic neurons activates cortical neurons
Using a dependent block of sodium channels decreases what?
neuronal firing rate
Decreasing ____ and increasing ____ can lead to a decrease in seizure activity?
- glutamate
2. GABA
Neurons in the thalamus are dependant on what for depolarization?
- calcium channel pacemakers
- blocking these channels slows the pacemaker
What drugs can be used to treat a partial (focal) seizure?
- carbamazepine, phenytoin or valproate
What drugs can be used to treat a tonic-clonic seizure?
carb., phenytoin pr valproate
What drug can be used to treat a generalized absence seizure?
ethosuximide
What drugs can be used to treat a generalized tonic-clonic or absence seizure?
valproate
What drugs can be used to treat an atypical generalized seizure?
valproate
How does carbamazepine work?
- inhibits voltage gates sodium channels
- similar to TCAs
- induces its own metabolism
- initial half life of 36 hours- goes down to 8-12 hours
- can enhance metabolism of many other anti epileptics including phenytoin and valproate toxicity
What are the adverse effects and toxicities of carbamazepine?
double vision, ataxia, nausea, drowsiness
- skin rash is common, leukopenia (lower than normal number of white blood cells)
How does phenytoin work?
- blocks voltage gated Na channels
- absorption differs among formulations
- dose dependent (saturation) metabolism- half life ranges from 12-36 hours
- highly bound to plasma proteins (decreases bioavailability)
- induces CYP3A4, increases metabolism of many drugs
- induces metabolism of carbamazepine, valproate, vitamin K and contraceptives(decreases effectiveness of contraceptives)
- metabolism is enhances by phenobarbital and carbamazepine, requires dose adjustment
What are the adverse effects of phenytoin?
- double vision and ataxia - balance problems, uncoordinated movements
- requires a dose adjustment
- gingival hyperplasia (gun inflammation). hirsutism (hair growth)
- mild peripheral neuropathy
- megaloblastic anemia - dysfunctional RBCs, can occur due to altered folate metabolism
- osteomalacia- decreased calcification of bone. Can occur due to altered vitamin D metabolism
How does phenobarbital work in epilepsy?
- enhances the inhibitory effects of GABA
- primidone is metabolized to phenobarbital
- metabolism is first order, half like is around 4 days
- drug interactions are common with vitamin K and oral contraceptives
- induces its own metabolism
What are the adverse effects associated with phenobarb?
- drowsiness, eye movements, ataxia, respiratory depression, decreased motor skills
- skin rash due to hypersensitivity
- psychological and physiological dependence
How does Gabapentin work?
increases release of GABA from neurons
- appears to decrease GABA metabolism
- does not induce of inhibit hepatic enzymes
- minimal binding to plasma proteins
What are the adverse effects of Gabapentin?
-sedation, dizziness, headache, temor and ataxia - GI effects (nausea and constipation)
How does topiramate work?
- inhibits voltage sensitive Na channels, increases GABA effects and inhibits glutamate receptors
- approved for adjunctive therapy
- metabolism is affected by other drugs
What are the adverse effects and toxicity of topiramate?
- fatigue, dizziness, mental slowing and nausea
Lamotrigine
- blocks voltage gated sodium channels
- used for adjective therapy
Adverse effects of lamotrigine
- dizziness, headache, skin rashes
How does ethosuximide work?
blocks voltage activated calcium channels
How does clonazepam work?
- enhances the inhibitory effects of GABA
Valproate
- voltage gated Na and Ca channels - enhances inhibitory effects of GABA
- binds plasma proteins
- inhibits metabolism os other drugs
What are the adverse effects associated with valproate?
- tremor in higher concentrations
- risk of spina bifida
What is given for status epileptics?
- IV diazepam or IV lorazepam are used to stop seizure
- phenytoin may then be initiated for longer term control
- anti-epileptics are gradually increased
Pregnancy requires tx considerations- what are they?
- always a challenge since AEDs can harm the fetus but so can uncontrolled seizures
- risk to fetus from uncontrolled seizures is greater
- lowest effect dose should be used
- only one drug at a time
- increase in dose is necessary during the course of the pregnancy
Which anti-epileptics enhance the metabolism of oral contraceptives?
-phenytoin and phenobarbital
Which drugs can cause osteomalacia?
phenytoin, phenobarbital
Which drugs enhance metabolism of other anti-epileptics?
- phenytoin, carbamazepine, phenobarbital
Which drug inhibits metabolism of other anti-epileptics?
- valproate
