Term
| WHAT ARE THE SEIZURE MAIN CATEGORIES? |
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Definition
1. PARTIAL (FOCAL) SEIZURES
2. GENERALIZED SEIZURES |
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Term
| WHAT ARE THE SUBCATEGORIES FOR PARTIAL SEIZURES? |
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Definition
1. SIMPLE SEIZURES
2. COMPLEX SEIZURES
3. SECONDARILY GENERALIZED SEIZURES |
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Term
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Definition
-LOCAL ORIGIN THAT MAY SPREAD
- FOCAL
- BRIEF ( 20-90) SECONDS
- NO LOC
- NO ALTERED CONSCIOUSNESS |
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Term
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Definition
-LONGER (< 2MIN)
+ LOC
- TEMPORAL LOBE
- AUTOMATISMS
- BEHAVIORAL CHANGES |
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Term
| SECONDARY GENERALIZED PARTIAL SEIZURES |
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Definition
-FOCAL SEIZURE BECOMES GENERALIZED INTO TONIC-CLONIC
- FOLLOWED BY +LOC |
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Term
| WHAT ARE THE SUBCATEGORIES FOR GENERALIZED SEIZURES? |
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Definition
1. TONIC-CLONIC SEIZURES
2. TONIC SEIZURES
3. CLONIC SEIZURES
4. MYOCLONIC SEIZURES
5. ATONIC SEIZURES
6. GENERALIZED ABSENCE SEIZURES |
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Term
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Definition
-GRAND MAL
- INITIAL TONIC RIGIDITY (15-30 SEC)
-SUBSEQUENT TREMOR
-EVENTUALLY CLONIC JERKING (60-120 SEC)
+LOC
- PT IS USUALLY STUPOROUS
(INCREASED MUSCLE TONE FOLLOWED BY SPASMS OF MUSCLE CONTRACTION AND RELAXATION |
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Term
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Definition
- BRIEF SPASMS
- OFTEN SECONDARY TO OTHER SEIZURE DISORDER
- OFTEN BENIGN
IE: HAPPENS WHEN YOU ARE FALLING ASLEEP |
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Term
| GENERALIZED ABSENCE SEIZURES |
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Definition
- SUDDEN ONSET
- BRIEF (10-30 SEC)
BRIEF + LOC WITH MINOR MUSCLE TWICHING AND EYE BLINKING
- ASSOCIATED WITH CHILDHOOD
- 3 Hz SPIKE AND WAVE ON EEG |
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Term
| WHAT ARE THE MECHANISMS OF SEIZURE GENERATION? |
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Definition
1. EXPERIMENTAL BLOCKADE OF GABA RECEPTORS CAUSES SEIZURES
2. EXPERIMENTAL ACTIVATION OF GLUTAMATE RECEPTORS (NMDA RECEPTOR) CAUSES SEIZURES
3. KINDLING - PERIODIC, LOW INTENSITY STIMULATION - CAN BE BLOCKED BY NMDA RECEPTOR INHIBITION (electrode in brain)
* withdrawal from barbituates or alcohol can be fatal since it lowers the seizure threshold |
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Term
| HOW ARE ABSENCE SEIZURES GENERATED? |
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Definition
- RARE
- ORIGINATE IN THALAMUS
- MAY BE ASSOCIATED WITH HIGH FEVERS
- CONGENITAL AND HEREDITARY FACTORS
- NEOPLASMS MAY CAUSE SEIZURES
- CAN DEVELOP AFTER INJURY OR STROKE |
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Term
| WHAT ARE THE MECHANISMS OF ANTIEPILEPTIC DRUGS? |
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Definition
1. BLOCKADE OF SODIUM (Na+) CHANNELS
2. BLOCKADE OF THALAMIC, T-TYPE Ca++ CHANNELS
3. ENHANCE GABA ACTIVITY OR INCREASE INHIBITORY PATHWAYS |
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Term
| MOA FOR PHENYTOIN, CARBAMAZEPINE, VALPROIC ACID |
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Definition
-BLOCKADE OF SODIUM CHANNELS
* blocks inactivated sodium channels
*slow rapidly firing neurons
* little effect on normal neurons |
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Term
| MOA FOR ETHOZUXIMIDE, VALPROIC ACID? |
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Definition
- BLOCKADE OF T-TYPE CALCIUM CHANNELS
* low threshold calcium channels
* pacemaker of thalamic neurons in absence seizures |
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Term
| MOA FOR PHENOBARBITAL, DIAZEPAM (BENZODIAZAPINES)? |
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Definition
- ENHANCE GABA ACTIVITY
- INCREASE INHIBITORY PATHWAYS
*this increases chloride conduction and also increases the seizure threshold |
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Term
| WHAT ARE THE COMMON SIDE EFFECTS OF ANTISEIZURE MEDICATIONS? |
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Definition
-SEDATION
-CNS DISTURBANCES
-TERATOGENESIS
-HYPERSENSITIVITY - STEVENS-JOHNSON SYNDROME
-GI DISTURBANCES |
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Term
| WHAT ARE THE GENERAL PRINCIPALS OF TREATMENT? |
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Definition
1. STOP SEIZURES WITHOUT SIDE EFFECTS
2. MONITOR PLASMA DRUG LEVELS
* go through P450 metabolism
* most drugs are 0th order so metabolized by liver and is saturable mechanism
* kinetics are complicatied
*many interactions
*NARROW therapeutic indexes
- USE SINGLE DRUG IF POSSIBLE |
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Term
| WHAT ARE THE PHARMACOKINETICS TO CONSIDER? |
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Definition
1. MOST METABOLIZED BY P450'S
2. SLOW, SATURABLE METABOLISM
3. PHENYTOIN, CARBAMAZEPINE, PHENOBARBITAL ALL INDUCE P450'S
4. MAY BE HIGHLY PROTEIN BOUND |
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Term
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Definition
MOA
- prolongs inactivation Na channels
- inhibits rapid firing neurons
USES
- partial seizures
- gen. tonic-clonic seizures (both primary and secondary)
- NOT effective for absence seizures
***makes absence seizures worse
- absorption is variable
- NOT water soluble so NOT injected
- highly protein bound ( may affect thyroid Fx tests)
- 1st order eliminations at low doses
- 0th order eliminations at high doses
-t1/2 from 12-36 hrs
- therapeutic range is 10-20 ug/ml |
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Term
| PHENYTOIN DRUG INTERACTIONS |
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Definition
- drugs that can alter p450's
* phenobarbital
* carbamazepine
- Phenytoin itself increases plasma levels of many drugs ie: warfarin bc inhibits p450s
- Phenytoin decreases plasma levels of many drugs ie: OC bc it also induces p450's |
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Term
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Definition
1. Nystagmus - eye flutter (not dose limiting)
2. Diplopia and Ataxia - req dose adjustment
3. Sedation at high plasma levels
4. Gingival hyperplasia, hirsutism ( amlodepine also)
5. Long-term - coarsening of facial feat., mild peripheral neuropathy, abnormal vit D metabolism (osteomalacia)
- skin rash - discontinue use- risk of SJS
- Pregnancy category D |
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Term
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Definition
MOA
* blocks Na channels
* inhibits high frequency, repetitive firing
* inhibits NE release and reuptake
* May potentiate GABA action
USES
* DOC (drug of choice) PARTIAL SEIZURES
* not used often for Gen. Tonic-clonic seizures
* Trigeminal neuralgia
* Bipolar disorder |
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Term
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Definition
1. Diplopia and Ataxia (divide doses decreases peak concentration in plasma so less CNS disturbances
2. GI upset
3. Drowsiness
4. Idiosyncracy blood dyscrasias ( messes with blood cell production)
5. Mild leukopenia
6. hypersensitivity - SJS
7. Pregnancy category D |
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Term
| CARBAMAZEPINE DRUG INTERACTIONS |
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Definition
1. increases metabolism of : phenytoin, ethosuximide, valproic acid, clonazepam, haloperidol, OCs
2. Carbamazepine's metabolism is increased by phenytoin. phenobarbital, and valproic acid
- Carbamazepine's metabolism is inhibited by :
Cimietidine, floxetine, isoniazid, erythromycin |
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Term
| CARBAMAZEPINE DRUG INTERACTIONS |
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Definition
1. increases metabolism of : phenytoin, ethosuximide, valproic acid, clonazepam, haloperidol, OCs
2. Carbamazepine's metabolism is increased by phenytoin. phenobarbital, and valproic acid
- Carbamazepine's metabolism is inhibited by :
Cimietidine, floxetine, isoniazid, erythromycin |
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Term
| CARABAMAZEPINE METABOLISM |
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Definition
- absorption variable but complete
- higher doses should be given after meals as to slow absorption
- induces cytochrome P450s (increases OC metabolism, and induces its own metabolism)
- Therapeutic range 6-12 ug/mL |
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Term
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Definition
MOA
* as anticonvulsant is not well known
* prolongs opening of Cl channel at GABA receptor
* alter Na and Ca conductance at high concentrations
* inhibits excitatory, glutamate responses |
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Term
PHENOBARBITAL 1.uses 2.drug interaction
3. toxicities |
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Definition
USES
* partial seizures
* gen. Tonic-clonic seizures
DRUG INTERACTIONS
*induction of P450s increases metabolism of - phenytoin, carbamazepine
TOXICITIES
* CNS depressant
* Pregnancy cat D - teratogenic |
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Term
| ETHOSUXIMIDE (Zarontin) MOA, USE |
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Definition
MOA
* reduces T-type Calcium current in thalamic neurons
* inhibits pacemaker for rhythmic cortical discharge
USE
* DOC for ABSENCE SEIZURES |
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Term
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Definition
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Term
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Definition
| CARABAMAZEPINE (TEGRETOL) |
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Term
| DOC FOR GEN. TONIC-CLONIC SEIZURES |
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Definition
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Term
| PRMIDONE (MYSOLINE) HAS SIMILAR METABOLISM TO WHAT DRUG? |
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Definition
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Term
| ETHOSUXIMIDE USES, METABOLISM, DRUG INTERACTIONS, TOXICITIES |
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Definition
USE
* absence seizures
DRUG INTERACTIONS
* Valproic acid inhibits metabolism and increases half life
METABOLISM
* well absorbed orally
* completely metabolized by LIVER
* variable half life of 18-72 hrs, mean of 40hrs
TOXICITIES
* gastric mucosa irritation (better slow increase of dose or dividing doses)
* Lethargy, fatigue, headache, dizziness, hiccups, euphoria
* SJS rare
* Pregnancy cat C - no evidence of teratogenicity in humans but yes in animals |
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Term
| WHAT DRUG INHIBITS ETHOSUXIMIDE METABOLISM AND INCREASES ITS HALF LIFE? |
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Definition
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Term
| MOA FOR VALPROIC ACID ( DEPAKENE) |
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Definition
1. blocks high-frequency repetitive firing of neurons
2. probably blocks Na channels
3. may enhance GABA activity
4. may hyperpolarize membranes by increasing K conductance |
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