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67 Cards in this Set
- Front
- Back
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What is epilepsy?
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chronic disorder characterized by recurrent seizures
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what are seizures?
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finite episodes of brain dysfunction resulting from abnormal discharge of cerebral neurons arising from the cerebral cortex
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what is the pathophys of seizures?
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unknown but may be the following:
1. defective synaptic functioning 2. decrease in inhibitory activity 3. increase in excitatory activity |
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What is a simple partial seizure?
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1. there is no loss of consciousness
2. there is abnormal activity of a single limb or mm group 3. duration 20-60 seconds |
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What is a complex partial seizure?
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1. there is a LOSS of CONSCIOUSNESS
2. there is abnormal activity of chewing movements, diarrhea, urination 3. duration 30-120 seconds |
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what can happen to simple or complex partial seizures?
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They can become secondarily generalized tonic-clonic seizures.
Duration 1-2 minutes |
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what are generalized seizures?
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1. no evidence of localized onset
2. may become convulsive or nonconvulsive 3. IMMEDIATE LOSS of CONSCIOUSNESS |
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What is a tonic-clonic seizure?
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Aka GRAND MAL
1. Not preceded by a partial seizure. 2. LOSS of CONSCIOUSNESS 3. TONIC mm relaxation 4. CLONIC mm contraction 5. Duration 1-2 minutes 6. After seizure, period of confusion and exhaustion |
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What is an absence seizure?
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Aka PETIT MAL
1. occurs in kids 3-5 yo until puberty 2. brief abrupt self-limiting loss of consciousness 3. STARES and RAPID EYE-BLINKING 4. Duration usually <10 seconds, rarely more than 45 seconds |
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What does the EEG show in absence seizure?
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EEG shows a spike and wave pattern
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What are other generalized seizures?
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Atonic (loss of postural tone)
Tonic only Clonic only Myoclonic rare Infantile (epileptic syndrome, not seizure type and are mentally retarded) Febrile (usually tonic clonic) Status Epilepticus |
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What is status epilepticus?
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1. repeated seizures prolonged at least 30 minutes
2. can be most forms (convulsive, nonconvulsive, partial, subclinical) |
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What is the most common seizure in status epilepticus?
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Generalized tonic-clonic, which is a
LIFE THREATENING EMERGENCY requiring immediate CV, RESP, MET management and PHARM tx. |
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What is the pharm tx for status epilepticus?
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IV ONLY LORAZEPAM
If seizures continue: IV PHENYTOIN, FOSPHENYTOIN If that doesn work: IV PHENOBARBITOL If that doesn't work the seizure is refractory and general anesthesia is used: MIDAZOLAM, PROPOFOL, BARBITUATES |
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What NTs mediate the most synaptic transmissions in the brain?
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AAs: GABA inhibitory and GLUTAMATE excitatory
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What happens when you microinject GABA-R antagonists or Glutamate-R agonists in the brain?
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trigger seizures
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What happens when you microinject GABA-R agonists or Glutamate-R antagonists in the brain?
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inhibit seizures
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What do these studies support?
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That pharm regulation of synaptic function can regulate propensity for seizures.
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What are the classes of epileptic drugs?
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Drugs that block voltage gated ion channels
1. Na+ 2. T-type Ca++ Drugs that affect synaptic transmission 1. Enhance GABA 2. Reduce Glutamate |
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What are the drugs that block voltage gated Na+ channels?
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Phenytoin
Carbamazepine Lamotrigine Zonisamide Phenobarbital Valproate Topiramate |
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What is the result of blocking Na+ gated ion channels?
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BLOCK ACTION POTENTIALS in GLUTAMINERGIC NEURONS
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What are the drugs that block voltage gated Ca++ channels?
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Ethosuximide and valproate
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What is the result of blocking Ca++ gated ion channels?
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PREVENT ABSENCE SEIZURES
by inhibiting current b/t thalamus and cortex. |
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What are the drugs that enhance GABAnergic postsynaptic neurotransmission?
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Direct action ENHANCING GABA-R Cl- ion influx:
BENZOs BARBITUATES TOPIRAMATE |
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What are the effects of increasing Cl- influx?
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HYPERPOLARIZE neurons and DECREASE tendency to FIRE
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Which drugs enhance the presynaptic GABAnergic neurotransmission?
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TIAGABINE
VIGABATRIN GABAPENTIN |
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Which drug inhibits reuptake of GABA and keeps GABA in the synaptic cleft (like cocaine and NE)?
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TIAGABINE
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Which drug inhibits degradation of GABA by inhibiting GABA aminotransferase?
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VIGABATRIN
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Which drug increases GABA release from vesicles into synaptic cleft?
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GABAPENTIN
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Which drugs reduce the postynaptic glutamatergic neurotransmission?
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PHENOBARBITAL
TOPIRAMATE |
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What is the mechanism of phenobarbital and topiramate?
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Block post-synaptic Na+ channels on the glutamate receptor.
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Which drugs reduce the presynaptic glutamatergic neurotransmission?
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GABAPENTIN
PREGABALIN |
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What is the mechanism of gabapentin and pregabalin?
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Decrease glutamate release by blocking presynaptic voltage-gated Ca++ channels.
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What are the drugs of choice for simple
and complex generalized tonic-clonic seizures? |
DOC:
Carbamazepine Oxcarbazepine Lamotrigine (can be mono tx) Phenytoin (valproate, topiramate alternatives) |
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What are the adjuvants for simple and
complex generalized tonic-clonic seizures? |
Gabapentin
Pregabalin Zonisamide |
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What are the secondary drugs for
simple and complex generalized tonic clonic seizures? |
PHENOBARBITAL
d/t AE sedation, depression, agitation |
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What are the drugs of choice for
generalized tonic-clonic seizures? |
DOC
Valproate (best) Carbamazepine Phenytoin |
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What are the drugs of choice for generalized absence seizures?
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DOC
Ethosuximide Valproate |
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What is the drug of choice for generalized atypical absence seizures?
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DOC
Valproate |
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What are secondary choices for generalized absence seizures?
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Clonazepam
AE: sedation and tolerance Acetazolamide AE: tolerance |
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What is the drug of choice for myoclonic seizures?
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DOC
Valproate |
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What is difficult about tx for atonic seizures?
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Pt are often refractory to all drugs. Pt has to wear helmet at all times (just fall to ground).
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What is the drug of choice for atonic seizures?
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None really.
Benzo may improve or make worse. Felbamate is effective but toxic. |
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What is the drug of choice for infantile spasms?
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DOC
Corticotropin Glucocorticoids Vigabatrin |
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What is the drug of choice for febrile convulsions?
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DOC
Seizure <15 minutes SUPPORTIVE Tx only Seizure >15 minutes DIAZEPAM IV or rectal |
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What is the drug of choice for other convulsive emergencies?
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NOT EPILEPTIC
DOC Drug induced in nonepileptic patients: DIAZEPAM LORAZEPAM PHENOBARBITAL |
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What are breakthrough seizures?
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Breakthrough seizures experienced by epileptic patients who are well-controlled on anti-epileptics
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What is the drug of choice for breakthrough seizures?
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DIAZEPAM rectal gel
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What do carbamazepine, phenobarbital, and phenytoin all do?
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Induce cyt P450
"THE INDUCERS" |
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Which anti-epileptic causes hepatotoxicity?
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VALPROATE
(risk is greatest in <2 yo and those on multiple anti epileptic drugs. |
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What other effect does valproate cause?
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INHIBITS cyt P450
INHIBITS its own METABOLISM |
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What are the AE of phenytoin?
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MUST KNOW THESE:
*Nystagmus, diploplia, ataxia *Gingival hyperplasia *Coarsening of facial features in children |
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What are the AE of carbemazepine?
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Aplastic anemia, agranulocytosis, thrombocytopenia (rare)
Skin rash |
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What are the AE of vigabatrin?
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LT tx associated with IRREVERSIBLE
visual field defects in 1/3 of patients |
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When do you discontinue tx?
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*If pt seizure free for 3-5 yrs
*Slow *One at a time |
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Which drugs cause withdrawal seizures?
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BENZO and BARB
*discontinue gradually to avoid withdrawal seizures |
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What are the effects of overdose?
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Common in suicide attempts
Rarely lethal May experience respiratory depression |
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Which drugs are used in pregnancy?
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All drugs should not be used
Valproate specifically has a high rate of fetal malformations. FOLIC ACID can reduce neural tube defects. |
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What do enzyme-inducing antiepileptic drugs do to the fetus?
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Increase degradation of vitamin K.
Can cause bleeding in newborn. Vitamin K can be given to mother in the final month of pregnancy and to the newborn. |
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What else can CARB be used for?
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neuropathic pain
bipolar disorder (alt. to lithium) |
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What else can GABAPENTIN be used for?
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neuropathic pain
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What else can LAMOTRIGINE be used for?
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bipolar disorder (alt. to lithium)
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What else can PREGABALIN be used for?
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neuropathic pain
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What else can TOPIRAMATE be used for?
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migraine
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What else can VALPROATE be used for?
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bipolar disorder (alt. to lithium)
migraine |
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What happens to a 1/3 of patients on medications?
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continue to experience seizures
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What are nonpharm approaches to those patients?
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*Surgery - resect epileptic focus
*Ketogenic diet - 4pt fat, 1pt protein, 1pt carb l/t -->ketosis which has a direct antiseizure effect *Vagus n stimulation - intermittent stimulation of the L vagus n w/implanted pacemaker. Patient activates the device when they feel a seizure is imminent. |
