Flashcards in AntiEpiletic Drugs Deck (34):
What is Epilepsy? What are seizures?
Epilepsy: heterogenous symptom complex: a chronic disorder characterized by recurrent seizures
Seizure: finite episodes of brain dysfunction resulting from abnormal discharge of cerebral neurons arising from the cerebral cortex
Lets talk about the different types of seizures. First up are the partial seizures, what are the different types of partial seizures?
Simple Partial Seizures
Complex Partial Seizures
Partial with Secondarily Generalized Tonic Clonic Seizures
First up, simple partial seizures, what are these?
--abnormal activity of a single limb or muscle group
--duration 20-60 seconds
Second up, complex partial seizures, what are these?
Complex sensory hallucinations, mental distortion and LOC
--originate from the temporal lobe
--duration: 30-120 seconds
Third up, partial with secondarily generalized tonic clonic seizures, what are these?
Simple or complex partial seizure evolves into a tonic clonic seizure with LOC
--lasting 1-2 minutes
Next are the generalized seizures. What are the different types?
May be convulsive or nonconvulsive
--patient has immediate LOC
Tonic Clonic Seizures ( grand mal)
Absence Seizures (petit mal)
Atypical Absence seizures
First up are the tonic clonic seizures (grand mal), what are these?
Most commonly encountered
--LOC, followed by tonic, then clonic phases
--followed by period of confusion and exhaustion
Second up are the absence seizures (petit mal), what are these?
Brief, abrupt and self limiting LOC
--onset occurs at ages 3-5 y/o and lasts until puberty.
--patient stares and exhibits rapid eye blinking
--EEG shows 3 Hz spike and wave pattern that emerges abruptly
Third up, are the atypical absence seizures. what are these?
More intense muscle involvement and a longer recovery time
--respond poorly to treatment and are often associated with severe neurologic treatment
What are the various other types of generalized seizures ?
Atonic: sudden loss of postural tone
Tonic: muscles contract and consciousness is altered for about 10 seconds
Clonic: very rare. young children
Myoclonic: short episodes of muscle contractions that may reoccur for several minutes
Febrile: high fever in young children
Status Epileptics: repeated seizure or a seizure prolonged for at least 30 minutes. -- generalized tonic clonic epilepticus is a life threatening emergency requiring immediate cardiovascular, resp and metabolic management.
What is the general mechanism for seizures?
Defective synaptic function might lead to seizure
--a decrease in inhibitory synaptic activity or an increase in excitatory activity
What neurotransmitters mediate the bulk of synaptic transmission in brain?
GABA: main inhibitory
Glutamate: main excitatory
--therefore antagonist of the GABAa receptor or agonist of the glutamate receptor subtypes (NMDA or AMPA) trigger seizures
Therefore pharmacological regulation of synaptic function can regulate the propensity for seizures
Moving on the drugs and their MOA. What drugs block voltage gated Na channels?
may also contribute to effects of Phenobarb, valproate and topiramate
What drugs block T type Ca2+ channels?
Absence seizure involve neuronal activity between thalamus and cortex
--a low threshold calcium current ( t type Ca2+ current) governs oscillatory responses in thalamic neurons
Reduction of this current by Ethosuximide and Valproate i
Now there are drugs that affect synaptic transmission. What drugs enhance GABAergic neurotransmission?
--direct action on the GABAa receptor: benzos, barbiturates and topiramate
--inhibition of reuptake of GABA: Tiagabine
--Inhibition of degradation of GABA: Vigabatrin is an irreversible inhibitor of GABA aminotransferase, the enzyme responsible for degradation of GABA
What drugs reduce glutamatergic neurotransmission?
--Phenobarbital and Topiramate: inhibit excitatory responses induced by glutamate
--Gabapentin and Pregablin: decrease glutamate release; this effect is a consequence of blockage of presynpatic voltage gated Ca2+ channels.
--Levetiracetam: binds to synaptic vesicle glycoprotein 2A (SC2A)
The aim of therapy is total seizure freedom within clinically significant adverse effects. What are some general principles to consider when starting antiepileptic treatment?
1. Tx should be started with a single drug
2. Dosage should be gradually titrated to that which is maximally tolerated and/or produces optimal seizure control
3. Tx should be monitored regularly
4. Combo therapy should be attempted only if at least two adequate sequential trials of single agents have failed
Moving on to choice of drug, this depends on the type of seizure experienced by the patient. First up, partial and secondarily generalized tonic clonic seizures. what drugs are used?
What drugs are used for tonic clonic seizures?
What drugs are used for Absence Seizures?
DOC: ethosuximide and valproate
-if tonic clonic seizures emerge during therapy valproate is the drug of choice
Valproate is preferred for atypical absence seizures
What drugs are used for Myoclonic Seizures?
Topiramate can be used
Levetiracetam: adjunctive therapy
What drugs are used for Atonic Seizures?
Refractory to all available meds
--valproate and lamotrigine may be helpful
Lets talk alittle about febrile convulsions. What are these?
Seizures associated with an elevated temp greater than 38C in a child younger than 6 years of age
--with no CNS infection or inflammation or metabolic abnormality
Tx is supportive if seizures last less than 15 minutes
More than 15 minutes diazepam IV or rectally
Status epilepticus, what is the management?
Most common: generalized tonic clonic
--life threatening emergency
--goal of tx is rapid termination of seizure activity
--drugs given IV
--give a benzo like Lorazepam IV (much longer duration of antiepileptic action than diazepam)
If seizures continue in status epilepticus what is done?
IV phenytoin or fosphenytoin
--if benzos and phenytoin fail then IV phenobarb is given but respiratory complication is a common complication
And if all this fails the seizure is refractory
--general anesthesia should be instituted
What are other types of convulsive emergencies?
Drug overdose or poisoning
--controlled via diazepam, lorazepam or phenobarb all given IV
What are breakthrough seizures? And how are they managed?
Seizures experienced by epileptic patients who are on antiepileptic therapy
--diazepam rectal gel is used
Next are side effects. Just listed here are the bolded high yield side effects, however look at the chart in the notes for other side effects.
1. Carbamazepine: aplastic anemia, agranulocytosis
2. Phenytoin: gingival hyperplasia
3. Benzodiazepine: sedation, tolerance, dependence
4. Phenobarb: sedation, ataxia, drowsiness. Tolerance, dependence. Cognitive impairment and Hyperactivity
5. Valproic Acid: Hepatotoxicity
6. Felbamate: Aplastic Anemia, hepatotoxicity. For refractory epilepsy
7. Gabapentin: sedation and drowsiness
8. Lamotrigine: Rash, stevens-johnson syndrome. should be discontinued at the first sign of rash
9. Vigabatrin: Visual field loss
Antiepileptic drugs are often associated with skin rashes: which are they?
Lamotrigine (Black box warning about life threatening skin reactions.. should be discontinued if rash noticed)
Finally what is discontinuing antiepileptic therapy?
If a patient is seizure free for 3-5 years, gradual discontinuation of antiepileptic drugs is warranted
--should be done slowly
Antiepileptic drugs are common agents taken in intentional drug overdoses. What happens?
CNS depressants: but rarely lethal
Most dangerous effect is respiratory depression
--tx is supportive, stimulants should not be used
There is good evidence of an increased risk of congenital malformations in infants born of women taking antiseizure drugs. Most pregnant patients exposed to antiepileptic drugs deliver normal infants. However, fetal exposure to which drugs are teratogenic?
Valproate (spina bifida)
Phenobarb (cardiac defects and oral clefts)
--congenital malformations with developmental delay
Seizure drugs should be monotherapy
Phenytoin: fetal hydantoin syndrome
Topiramate: risk of oral cleft
Lower risk drugs: Lamotrigine, Levetiracetam, and Gabapentin
Why is vitamin K supplementation recommended for the mother in the final month of pregnancy and for the newborn?
Phenytoin, Phenobarb, Primidone and Carbamazepine
--cross the placenta and may increase the rate of oxidative degradation of vitamin K in the fetus