Module 3 Section 2 (Seizures) Flashcards
True or false: seizure disorders are the second most common chronic neurological disorder after stroke.
True
Approximately 7% to 10% of the population will have at least one seizure in their lifetime, while about 1% of the population will have recurrent seizures (e.g. epilepsy).
Why do seizures occur?
The cause of about half of seizures are unknown, while the other half of seizures occur due to CNS trauma, tumours, metabolic or toxic states (e.g. brain deprived of oxygen, or inflammation of the brain), or drugs (e.g. alcohol withdrawal)
How are seizures broadly classified?
1) Generalized seizures
2) Partial seizures
What is the difference between generalized and partial seizures?
Generalized seizures: they account for approximately 40% of all seizures. These seizures involve the entire CNS, arising in both cerebral hemispheres, and are accompanied by loss of consciousness.
- They are sub-divided into several classes (e.g. tonic-clonic seizure, status epilepticus) based on the type of movement and duration of loss of consciousness that occur during the seizure.
- Recovery can take anywhere from minutes to hours, depending on the type of generalized seizure. The postictal period (the period of altered state of consciousness that occurs immediately after a seizure) is often accompanied by a gradually clearing delirium.
Partial (focal) Seizures: they account for the other 60% of seizures. These seizures involve focal areas of the brain and therefore have more restricted symptoms.
- They may involve motor disturbances, as well as alterations of perceptions (e.g. taste, smell) or behaviour (e.g. violence, disruption of consciousness).
Explain the mechanism of seizures.
Seizures result from sudden repeated spontaneous discharge of groups of excitatory neurons in the central nervous system (CNS).
- This synchronous discharge may radiate to involve surrounding areas of the brain, and the extent of the involvement of the brain determines the classification and characteristics of the seizure.
The major excitatory neurotransmitter in the CNS is glutamate, and the major inhibitory neurotransmitter is GABA. If the excitatory glutamate input exceeds the inhibitory GABA input, the neurons in the CNS will “fire”. Most excitatory neurons in the CNS are glutamatergic neurons.
Since seizures result from synchronous discharge of excitatory neurons in the CNS, then seizures must involve glutamatergic neurons.
Are anti-seizure therapies effective?
Anti-seizure therapies are not completely effective.
In fact, complete control of seizures only occurs in about 50% of people, while significant improvements in seizures occurs in an additional 25% of people. This means that 25% of people suffering from seizures are not able to find relief from currently available medications.
Strategies for controlling seizures aim to decrease glutamate-induced excitation. What are the 3 mechanisms that can accomplish this?
1) Increasing the inhibitory input to the neuron to suppress firing: This can be accomplished by increasing GABA activity in the brain.
- A few common anticonvulsants that act by increasing GABA activity are valproate (i.e. valproic acid), phenobarbital (a barbiturate), and benzodiazepines.
2) Blocking electrical activity of the nerve to slow the nerve impulses: this can be accomplished by blocking Na channel electrical activity, which will slow the conduction of the nerve impulse.
- Examples of anticonvulsants that work by blocking nerve impulse transmission are lamotrigine and valproate.
3) Decreasing excitatory transmission: this can be accomplished by decreasing the release of glutamate at the synapse.
- Ex: Lamotrigene acts in this manner, in addition to blocking sodium channels.
Explain the pharmacokinetics of anticonvulsants. Where is it absorbed? And what type is used depending on the seizure type?
Most anti-seizure drugs have similar pharmacokinetics, since they all have to be able to cross the blood-brain barrier and enter the CNS.
Absorption of these drugs after oral administration is about 80-100%, and the drugs are cleared primarily by the liver.
In general, the anticonvulsant used depends on the type of seizure.
- Drugs used for partial seizures are essentially the same for all types of partial seizure, while drugs used for generalized seizures are more likely to be determined by the individual seizure type.
What are some adverse effects for anticonvulsants?
- CNS: sedation, tremor, ataxia, cognitive and visual impairment
- Gastrointestinal: nausea, vomiting, and diarrhea
- Hepatic: elevated hepatic enzymes, generally asymptomatic, periodic monitoring of liver function is required
- Immune system: benign skin rashes occur in 5% to 20% of patients on anticonvulsants. However, severe and potentially fatal skin hypersensitivity reactions can also occur.
True or false: adverse effects to anticonvulsants can be minimized by starting with a low dose and slowly increasing the dose.
True
“Start low, go slow”
Do this by dividing doses, or by administering the drugs with meals.
The classic anticonvulsants such as valproate are generally associated with more adverse effects than newer agents such as lamotrigine.
What are the drug interactions to watch out for when taking anticonvulsants?
Most anticonvulsants induce biotransformation enzymes. Consequently, the metabolism of concurrently administered drugs is increased, resulting in a decrease in the duration of action of concurrent drugs.
This can lead to a loss of therapeutic effect of concurrently administered drugs unless appropriate dosage adjustments are made.
Name some steps a healthcare worker could take when prescribing anticonvulsants to a patient to minimize potential drug-drug interactions.
A healthcare worker would:
- Limit coadministration: prescribe additional medication only when there is a clear clinical indication.
- Monitor response: carefully monitor clinical response after addition or removal of drugs. Consider the possibility of an interaction if there is an unexpected change in response. Continue the observation for a period of time consistent with the pharmacokinetic and pharmacodynamic properties of the drugs involved.
- If necessary: adjust the dose.
Discuss the toxicity of anticonvulsants.
Even though anticonvulsants act by decreasing CNS activity, they are rarely lethal.
The most dangerous effect of anticonvulsant overdose is respiratory depression, which can be potentiated by other CNS depressants, such as alcohol.
Explain the ways in which anticonvulsants can have adverse effects in all individuals, and then in pregnant women specifically.
Anticonvulsants can cause a variety of adverse effects including severe skin rashes, GI disruption, and cognitive and visual impairment.
Pregnant women should be especially cautious, as some anticonvulsants are teratogenic and can cause neural tube defects in the fetus.
Ex: valproate is teratogenic, causing neural tube defects, and disrupting the biosynthesis of folic acid. Since 50% of all pregnancies are unplanned, folate supplementation is initiated in all women of child-bearing age who are prescribed any of the anticonvulsants.
Although it’s important to minimize exposure to anticonvulsants while pregnant to decrease the risk of teratogenicity, it is also important to not allow maternal seizures to go unchecked.
True or false: withdrawal from anticonvulsant drugs occurs.
Withdrawal from anticonvulsant drugs does occur, and the severity depends on the drug being withdrawn.
Withdrawal can cause increased frequency and severity of seizures. As such, it is prudent to gradually discontinue the drug.
In children, almost half the recurrences occur within 6 months of medication withdrawal, and 60-80% occur within 1 year of stopping the drugs. More than 80% of recurrences occur within the first 5 years.
