Epilepsy

seizures
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seizures
_____ are episodes of abnormal discharge of brain neurons resulting in abnormal brain function typically lasting a short period of time
isolated
a seizure is an _____ event perhaps precipitated by a high fever or a toxin which induced an aberrant neuronal discharge
epilepsy
_____ is a condition distinguished by recurrent seizures
predisposing factors
-sleep deprivation
-hyperventilation
-fever from underlying illness
-hormonal changes occurring during menses
-drug or alcohol ingestion

these are all _____ _____ for epilepsy
secondary or acute
-several acute metabolic conditions
-infections
-medications
-alcohol or drug withdrawal
-viral meningitis
-overdose of insulin

these are all causes of _____ or _____ seizures
focal onset
_____ _____ seizures begin in a localized area of the brain, although there may be generalization to involve both hemispheres
consciousness
focal onset aware seizures (simple partial seizures) typically result in no alteration of _____, and the first clinical and EEG change indicated an initial activation of nerve cells in a limited part of one cerebral hemisphere
focal onset
which type of seizure?

-minimal spread of the abnormal discharge resulting in the jerking of an extremity which can last as long as 90 seconds; EEG reveals a highly localized focus of abnormal firing tissue; postictal period is characterized by weakness in the affected extremity
complex partial
which type of seizure?

-begins with highly localized focus but then spreads to involve a larger portion of the brain; consciousness is altered; lip smacking, repeated swallowing, scratching, or even walking that the pt cannot remember; may last as long as 2 minutes; have postictial period associated with fatigue and ill feeling which can last several hours
secondarily generalized partial
what type of seizure?

-begins as partial seizure and progresses to a generalized tonic clonic seizure
generalized tonic clonic (grand mal)what type of seizure? -characterized by an initial *muscle rigidity* which slowly diminishes into a *relaxation phase* after *15-30 seconds*; then enters *phase of massive jerking of the entire body* lasting as long as *2 minutes*absence (petit mal)what type of seizure? -characterized by an abrupt onset and short duration usually *less than 10 seconds* and rarely more than 45 seconds; *consciousness is altered* and there may be *mild clonic jerking of the extremities and eyelids*status epilepticuswhat type of seizure? -*life threatening emergency* that requires immediate identification and treatment -seizure activity persisting for more than *30 minutes or 2 or more sequential seizures without recovery between them*antiepileptic drugs (AEDs)*status epilepticus* has precipitating factors which include *drug noncompliance* and *sudden withdrawal from _____ _____*, central nervous system infection, withdrawal from alcohol or sedative drugs, metabolic disturbances, sleep deprivation, stroke, trauma, or encephalitisreduce the number of seizures while limiting adverse effects of the medicationgoals of seizure drug therapy?monotherapya realistic goal for most pts is to completely control seizures, ideally achieved with _____ which is the use of only a single drugquality of lifein addition to controlling seizures, another goal should be improving the pts _____ _____ _____ by allowing a return to normal activities of daily living without restriction1) Partial Seizures 2) Primary Generalized Tonic Clonic Seizures 3) Secondary Generalized Tonic Clonic Seizures*Phenytoin (Dilantin)* is used in treating what 3 types of seizures?sodium*Phenytoin (Dilantin)* blocks high frequency repetitive firing of action potentials through actions on _____ channelspotassium and calcium*Phenytoin (Dilantin)* also alters _____ and _____ conductancesmembrane stabilizing*Phenytoin (Dilantin)* may also have _____ _____ effectsparahydroxyation*Phenytoin (Dilantin)* absorption: varies from pt to pt distribution: highly bound to plasma proteins metabolism: metabolized through _____non-linear*Phenytoin (Dilantin)* is metabolized in a _____ mannersaturable*enzymes* that metabolize *Phenytoin (Dilantin)* are _____ meaning that as the *amount of drug approached the saturation point, small incremental increases in a dose can result in disproportionally high serum levels*; must watch when adjusting doses!glucuronide metabolite*Phenytoin (Dilantin)* excretion?substrate inducer*Phenytoin (Dilantin)* -CYP450, CYP2C9, CYP1C19 for the _____ -CYP1A2, CYP2C9, CYP2D6, and CYP3A4 as the _____other drugs that are highly protein bound may displace phenytoin from plasma proteins (makes the drug less useful and needs a greater dose)*Phenytoin (Dilantin)* -drug interactions occur frequently and can have significant effects on clinical outcomes -what is the main issue with the plasma protein binding reactions with *Phenytoin (Dilantin)*?dose dependent (happens with toxic dose)which type of *Phenytoin (Dilantin)* adverse effect includes: -nystagmus, rash, confusion, hepatitis, and loss of smooth ocular pursuitnon-dose related (can occur with even one dose)which type of *Phenytoin (Dilantin)* adverse effect includes: -gingival hyperplasia, hirutsim, coarsening of facial features, peripheral neuropathy, altered vitamin D metabolism, depressed folate leaves, and megaloblastic anemiaCarbamazepine_____ is a *tricyclic agent closely related to TCAs*; also used for treating *bipolar depression*, trigeminal neuralgia, as well as epilepsy1) Focal Onset Seizures (partial) 2) Generalized Tonic Clonic Seizures*Carbamazepine* is used in treating what 2 types of seizures?sodium*Carbamazepine blocks _____ channels* to ultimately slow the firing of high frequency repetitive firing neuronsfood*Carbamazepine absorption*: completely from the GI tract; _____ slows down absorption distribution: well distributed but protein binding is NOT a concernCarbamazepinewhat drug has the following: *metabolism: induced its own enzymatic pathways*; dose adjustment needed during first month or so; completely metabolized with little or no unchanged drug recovered in the urineCarbamazepinewhat drug has the following: some pts complain of *diplopia at 7mcg*, some pts can tolerate levels as high as 10; *levels are drawn before morning dose of the drug*Carbamazepinewhat drug has the following: involved hepatic enzymes -- significant inducer of many CYP450 enzymes -*major substrate of CYP3A4, since induced and metabolized by CYP3A4, it can induce own metabolism* -can *increases the clearance of other drugs*Phenytoin and Phenobarbital_____ and _____ *induce Carbamazepine's enzymatic pathway*blood dycrasias -aplastic anemia and agranulocytosis*Carbamazepine Adverse Effects* include: -diplopia (7mcg) -ataxia -GI upset -unsteadiness -sedation ---> and also a risk of fatal _____ _____, which is why a *baseline and follow up blood test should be performed*Phenobarbitalwhat is the *most commonly used barbiturate based anti convulsant*?Phenobarbitalwhat drug has the following *MOA*: -has actions on *GABA* and enhancement of inhibitory stimuli -*prevents the spread of focus* -acts on *sodium & calcium channels*sodium and calcium*Phenobarbital* acts on the _____ and _____ *channels*1) Focal Onset Seizures (partial) 2) Grand Mal Seizures*Phenobarbital* is used in treating what 2 types of seizures?drowsiness and fatigue (due to it being a barbiturate base)*Phenobarbital* has 2 main side effects due to it being a barbiturate base... what are they? side effects can also include: -ataxia, blurred vision, N, V, Dcardiac arrhythmia, bradycardia, CNS, excitation or depressionwhat are the *major adverse events* of *Phenobarbital*?substrate inducer*Phenobarbital* has drug interactions such as -CYP2C19 which is a major _____ -CYP3A4 which is a strong _____1) Focal Onset Seizures (partial) 2) Grand Mal Seizures*Primidone* is used in treating what 2 types of seizures?Primidone_____ is a drug that is *metabolized to Phenobarbital and Phenymethylmalonnide* both which also have activity in suppressing these seizure typesPhenytoin and Phenobarbital*Primidone* has an MOA that is similar to _____ (sodium, potassium and calcium) and _____ (GABA, sodium and calcium)Primidonewhat drug has the following: -completely absorbed but rate of *absorption is slow* -distribution is small to moderate but only 30% is protein bound -*metabolism is fast*; levels accumulate slowly and therapeutic levels of Phenobarbital are achievedsedation and GI upsetwith *Primidone* the doses are initiated at *low levels* because _____ and _____ are prominent; gradually increasing the dose will help alleviate these problemsPure Petit Mal / Absence Seizures*Ethosuuximide* is used in treating what types of seizures?combination*Ethosuuximide* should be used in _____ with other agents!calcium*Ethosuuximide* has an *MOA* that is active in *suppressing _____ currents* in neuronal tissue; suppresses *paroxysmal spike and wave patterns* seen in *absence seizures* and depresses nerve transmission in motor cortexEthosuuximidewhat drug has the following: -completely absorbed and uniformly distributed throughout the body -not bound to salsa proteins -*given in 2 daily doses to avoid GI effects*substrate inducers and inhibitors*Ethosuuximide* has drug interactions with: -major _____ of CYP3A4 -concentration affected by _____ and _____ of CYP3A4hiccups*Ethosuuximide* has adverse effects like: N,V, *gastric distress*, lethargy, fatigue, headache, dizziness and _____1) Focal Onset Seizures (partial) 2) Generalized Onset Seizures (when used for monotherapy)*Valproic Acid* is used in treating what 2 types of seizures? (monotherapy)absence*Valproic Acid* can be used as an *adjunctive therapy* for multiple seizure types including _____ seizuresValproic Acidwhat drug does the following: 1) alters *sodium current* like Phenytoin and Carbamazepine to inhibit repeatedly firing of neurons 2) *increases levels of GABA* in the brain 3)drug may *hyperpolarize* neurons through actions on the *potassium channel*Valproic Acidwhat drug has the following: -well absorbed after oral administration -causes marked *GI irritation, can be reduced by taking with a meal or sustained release form* -distribution confined to *extracellular water* -metabolic clearance is slowinhibitor*Valproic Acid* has drug interactions as an *enzyme _____* and *decreases the clearance of many drugs*hepatotoxic*Valproic Acid* has Adverse Effects including: -N, V, heartburn, sedation, fine tremor -*fatal _____ reaction* -thrombocytopenia1) Complex Partial Seizures 2) General Tonic Clonic Seizures -adjunctive drug for Refractory Partial Seizures*Neurontin (Gabapentin)* is used in treating what types of seizures?GABA*Neurontin (Gabapentin)* has an *MOA* that *reduced presynaptic _____ release*Neurontin (Gabapentin)what drug has the following: -NOT metabolized -half life of *5-7hrs*drug interactions*Neurontin (Gabapentin)* does *not* demonstrate any major _____ _____ and thus *serum level monitoring is not required*fatigue, dizziness, blurred vision*Neurontin (Gabapentin)* has what 3 adverse drug reactions?adjunct therapy for Partial Onset Seizures I adults*Lyrica (Pregabalin)* is used in treating what types of seizures? (adjunct)calcium*Lyrica (Pregabalin)* has an *MOA* that binds to voltage gated _____ channels in the brain, inhibiting excitatory neurotransmitter releaseperipheral edema and weight gain*Lyrica (Pregabalin)* has 2 unique Adverse Drug Reactions... what are they? -others include dizziness, somnolence, ataxia, and blurred visionCNS*Lyrica (Pregabalin)* has an *increase sedative effect with other _____ drugs*fluid retaining*Lyrica (Pregabalin)* is known to *enhance _____ _____ effects of Thiazolidinelones* (Avandia, Actos)1) Focal Onset Seizures (partial) 2) Generalized Tonic Clonic Seizures 3) Lennox-Gastaut Seizures*Lamictal (Lamotrigine)* is used in treating what 3 types of seizures?amino acid sodium*Lamictal (Lamotrigine)* has a *MOA* that includes -acts on excitatory _____ _____ release -inhibits voltage sensitive _____ channels25mg every other day*Lamictal (Lamotrigine)* is titrated very slowly with increments as low as _____?Lamictal (Lamotrigine)what drug has the following: -fatigue, dizziness, diplopia, and ataxia -combination with other epileptic drugs may require dosing adjustment (inducer or inhibitor)1) Focal Onset Seizures (partial) 2) Myoclonic Seizures 3) Primary Generalized Tonic Clonic Seizures*Keppra (Levetiracetam)* is used in treating what 3 types of seizures? (adjunctive)1) inhibits voltage dependent *N type calcium channels* 2) facilitates *GABA-ergic* inhibitory transmission 3) reduced delayed *Potassium currents* -binds to synaptic proteins that modulate neurotransmitter releasedwhat are the 3 MOA of *Keppra (Levetiracetam)*?Keppra (Levetiracetam)what drug has the fowling: Adverse Drug Reactions... -somnolence, headache, *infection* -*behavior changes* such as *aggression* may require dose decreaseKeppra (Levetiracetam)what drug has the following: -does not undergo significant metabolism, *no cynically significant enzymatic drug interactions*Trileptal (Oxcarbazepine)what drug has the following: -*block sodium channels, resulting in stabilization of hyper excited neural membranes* and inhibits of repetitive neuronal firing -*increases Potassium conductance* and modulation of high voltage active *Calcium channels* contribute to anti convulsant effectmonotherapy or as adjunctive therapy for Partial Seizures in adults and children*Trileptal (Oxcarbazepine)* is used in treating what types of seizures?Trileptal (Oxcarbazepine)what drug has the following: -dizziness, somnolence, diplopia, fatigue, nausea, ataxia, vomiting, abnormal vision, abdominal pain, tremor, *dyspepsia, abnormal gait*Trileptal (Oxcarbazepine)what drug has the following: Safety Concerns -*hypersensitivity to Carbamazepine* -pt at risk for *hyponatremia*inhibitors inducersTrileptal (Oxcarbazepine) has interactions as: -_____ of CYP2C19 and -_____ of CYP3A4monotherapy and adjunctive therapy for Focal Onset Seizures (partial)*Vimpat (Lacosamide)* is used in treating what types of seizures? (monotherapy and adjunctive)sodium*Vimpat (Lacosamide)* has an *MOA* that stabilized neuronal membranes; enhances *slow activation of _____ channels* leading to inhibitor of repetitive neuronal firing*Vimpat (Lacosamide)what drug has the following: Adverse Drug Reactions: -dizziness, fatigue, blurred vision, diplopia, nausea, and tremordecrease*Phenytoin, Carbamazepine, and Phenobarbital* all of these drugs may _____ *Vimpat (Lacosamide)*'s concentrationadjunctive therapy for Focal Onset Seizures (partial)*Gabitril (Tiagabine)* is used in treating what types of seizures? (adjunctive)Gabitril (Tiagabine)what drug has the following: MOA: *enhances GABA activity* by binding the GABA uptake carrier* ADR: dizziness, headache, CNS depression, confusion, tremors, weakness interactions: CYP2D6 and CYP3A4 substratemonotherapy or adjunctive therapy for Focal Onset Seizures (partial) and adjunctive therapy for Generalized Tonic Clonic Seizures*Fycompa (Perampanel)* is used in treating what types of seizures? (monotherapy) (adjunctive)Noncompetitive Antagonist Glutamate receptor on postsynaptic neurons*Fycompa (Perampanel)* MOA?Fycompa (Perampanel)what drug has the following: -*Noncompetitive Antagonist Glutamate receptor on postsynaptic neurons* -ADR: dizziness, headache, fatigue, *weight gain* -interactions: major substrate of CYP3A4monotherapy or adjunctive therapy for Focal Onset Seizures (partial) and adjunctive therapy for Generalized Tonic Clonic Seizures used as adjunctive therapy for seizures associated with Lennox Gaustaut Syndrome*Topamax (Topiramate)* is used in treating what types of seizures? (monotherapy) (adjunctive)Topamax (Topiramate)what drug has the following: MOA: decreased seizure frequency by *blocking sodium channels* in neurons, by *enhancing GABA* activity and by *blocking glutamate activity* ADR: fatigue, dizziness, *psychomotor slowing, memory difficulty, speech problems*, nausea, tremors and *taste* interactions: CYP2C19 substrate inhibitoradjunctive therapy in Focal Onset Seizures (partial) in adults*Zonegran (Zonisamide)* is used in treating what types of seizures? (adjunctive)Zonegran (Zonisamide)what drug has the following: MOA: *blocks sodium channels and select calcium channels* ADR: potentially *fatal agranulocytosis and SJS* -fatigue, dizziness, ataxia, anorexia interactions: major substrate of CYP3A4Diazepamwhat drug? -IV administration for *Status Epilepticus* and adjunctive disorders -rectalLorazepamwhat drug? -IV for *Status Epilepticus*, may have *longer onset*Clonazepamwhat drug? -excellent activity for *absence seizures, infantile spasms, and Lennox Gastuat* -adjunctive in tx of myotonic, atonic, and generalized tonic conic seizuresClobazamwhat drug? -adjunctive tx of seizures associated with *Lennox Gastuat Syndrome*Phenytoin, Carbazaepine, and Phenobarbital, Benzos, VaproateTx for *Partial and Grand Mal Seizures*Ethosuximid and Valproic AcidTx for *Generalized Absence Seizures*Phenytoin~_____ has been linked to *cleft pallets, and fetal hydantoin syndrome*Valproic Acid~_____ can cause *spina bifida*3-4 yearsif a pt is *seizure free* for how long on a medication, it can be withdrawn slowlyPhenobarbital~_____ is *most difficult to withdraw* often requiring *weeks or months* of graduation dosage decreases