AntiEpiletic Drugs Flashcards
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?
NO LOC
- -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?
Phenytoin Carbamazepine Oxcarbazepine Lamotrigine Zonisamide 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?
Postsynaptically
–direct action on the GABAa receptor: benzos, barbiturates and topiramate
Presynaptically:
–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