Keppra (levetiracetam)MOA
•binds to SV2A•Metabolism: renally excreted (dose adjustment for renal impairment/dialysis)•Can be used for focal or generalized tonic-clonic seizures and status epilepticus, and somewhat effective for absence, myoclonic, and atonic seizuresDose: -Can be used for status at a starting dose of 60 mg/kg. -Regular dosing can start at 250 to 500 mg b.i.d. and up titrated to around 4000 adverse effects: - irritability and mood changes -Sedation or unsteadiness
Brivaracetam (Briviact) po, IVMOA
•MOA: binds to SV2A with 20-fold higher affinity than levetiracetam•Efficacy for focal seizures, but open-label data support use in generalized seizures
Briviact and other antiepileptic interactions
clearance is increased by enzyme inducers- this medication increases carbamazepine AND phenytoin concentration by 20%
Briviact adverse effects- what is a ratio for immediate switch from Keppra to Briviact
-less behavioral adverse effects and Keppra- Keppra: Briviact at 10: 1 - 15: 1 conversion ratio
Lamotrigine (Lamictal) MOA
-sodium channel blocker•Metabolism: liver through glucuronidation and eliminated in the urine
Lamotrigine (Lamictal) - what seizure should you avoid this medication - what does OCP in pregnancy due to these levels.- What other antiepileptic do need to watch out for the patient's on this
- medication did for focal seizures, generalized seizure, and absence - MAY WORSEN MYOCLONIC SEIZURES- estrogen ( OCPs) and pregnancy can INCREASE lamotrigine levels.- Valproic acid will INCREASE lamotrigine level
adverse effect of Lamotrigine (Lamictal)
•rash including severe rash like Stevens-Johnson Syndrome, dose related adverse effects like dizziness, blurred vision, unsteadiness, nausea, vomiting, headache, and tremor.
Clobazam (ONFI)- mechanism of action
•benzodiazepine- increases frequency of GABA-mediated chloride channel opening.
Clobazam (ONFI) is good for what seizures- adverse effects
-broad-spectrum but also has been approved for Lennox-Gastaut syndrome in patients 2 years and older.- at high doses nystagmus, incoordination, unsteadiness, and dysarthria
Valproic acid (Depakote)- mechanism of action
-multiple. -Gap up potential radiation -blocking T type calcium channels and sodium channels
valproic acid does what to other antiepileptics
REDUCES clearance of - carbamazepine-lamotrigine- phenobarbital-rufinamide
adverse effects of valproic acid
-nausea-Vomiting - weight gain -Tremor -hair loss -Thrombocytopenia -PCOS -hepatotoxicity / pancreatitis
avoid valproic acid in who
1. childbearing age -High risk of teratogenicity, around 10% 2. Metabolic disorder / MELAS 3. <2 years old
Zonisamide (Zonegran)- MECHANISM OF ACTION 3
- BLOCKS repetitive firing of voltage sensitive SODIUM canals- REDUCES voltage sensitive CALCIUM T channels - carbonic anhydrase inhibitor
unique side effects of Zonisamide (Zonegran)
1. weight loss2. cognitive slowing-think less than topiramate3. kidney stones (Up to 4% can be prevented with adequate hydration) think pretty similar to Topamax, in addition to the above they also have sedation, dizziness, nausea, fatigue, rarely depression or psychosis or rash
Topamax mechanism of action- use- dose
-multiple -antagonist of AMPA receptors- block sodium channel use: Focal and generalized seizure. Migraine weight loss. Dose: Started 25 mg daily or b.i.d.. Can increase up to 200 mg b.i.d.
adverse effects of Topamax
-cognitive slowing, word-finding difficulties -Sedation, dizziness - weight loss kidney stones -paresthesias
birth defects and Topamax2
1. oral clefts2. infant small for gestational age
Felbamate (Felbatol)- mechanism of action
-NMDA-R antagonism- GABA enhancement -block sodium channel
Felbamate (Felbatol)- inhibits ??-induces??
inhibits metabolism of -phenobarbital, phenytoin, valproic acid, warfarin inducer of cytochrome 3A 4. -Decrease carbamazepine level- OCPs less affective
Felbamate (Felbatol) effective for
-focal seizures -Generalized tonic-clonic in Lennox-Gastaut syndrome
adverse effect of Felbamate (Felbatol)
-aplastic anemia -hepatic failure (can result in death) CBC and LFTs at baseline Every 2 weeks for the 1st 6 months
Rufinamide (Banzel)- mechanism of action- what seizures is it particularly good for??
-sodium channel blockerBoard spectrum:- Lennox-Gastaut syndrome -drop seizures
what increases the level of Rufinamide (Banzel)
valproic acid. When combined with this the levels increase his much a 70%
Rufinamide (Banzel) adverse effect
-short QT interval -nausea, vomiting -Dizziness somnolence headache
Perampanel (FYCOMPA)- mechanism action- we will consideration should you have
•AMPA glutamate receptor antagonist- long half-life once a day dosing.- It accelerated of metabolism progesterone OCP use
Perampanel (FYCOMPA)- adverse effects
-aggression-hostility -homicidal ideation- box warningahh
phenobarbital- mechanism action- what seizures is it NOT effective for
- prolonging the opening of chloride channels on the GABA a receptor- good for focal and generalized tonic-clonic seizures- also, good for status epilepticus can be given at 20 mg/kg- NOT ABSENCE SEIZURES
adverse effects of phenobarbital- what is the fetus at risk for
-sedation -Depression -Long-term use associated with osteoporosis, Dupuytren contractures, and frozen shoulder.** increased risk of cardiac malformations and fetus
-what is the mechanism action of the medication for absence seizure- adverse effects
Ethosuximide (ZarontIN)- indicated ONLY for generalized absence seizures-blocks T type calcium channelAdverse effect: -Nausea, abdominal pain, anorexia, fatigue -ataxia -behavioral change.
Medications for focal seizures (mostly)6
1. Carbamazepine 2. Oxcarbazepine3. Eslicarbazepine4. Tiagabine5. Gabapentin (Neurontin)6. Phenytonin (Dilantin)
Carbamazepine (TEGRETOL) mechanism of action** how does affect enzymes
sodium channel blocker- potent enzyme inducer. Many drug to drug interactions*** induces its own metabolism
what other 2 antiepileptics increase carbamazepine
valproic acid and felbamate
adverse effects of carbamazepine** what is the HLA associated with SJS and TEN
-dizziness-Sedation -hyponatremia*** -leukopenia, rare aplastic anemia (sketchy)- Elevated levels: Diplopia, nystagmus, ataxia**SJS/TEN with HLA-B1502 in Asian Descent
Oxcarbazepine (TRileptal) -mechanism of action -*affects on other meds
- sodium channel blocker - Can reduce the efficacy of OCPs ( week induced cyto)remember :) for focal seizures
Oxcarbazepine (TRileptal) adverse effect
** hyponatremia, more common old patientson diuretic
EsLICarbazepine (Aptiom)
-sodium channel blocker - metabolized active metabolite through 1st passed metabolism - affected for focal seizures
EsLICarbazepine (Aptiom) adverse effects
similar to oxcarbamazepine but LESS- DROWSINESS -HEADACHE-FATIGUE, RASH, BLURRED VISION, DIPLOPIA AND HYPONATREMIA
Tiagabine (Gabitril) MOA
- THINK TIES UP THE GABA- inhibits GABA rate uptake at the synapse
Tiagabine (Gabitril) -what is effective for- what seizures could possibly worsen
- good for focal seizures only WORSEN generalized absence myoclonic seizures
Tiagabine (Gabitril) adverse effects
dizziness nervousness tremor depression
Gabapentin (Neurontin) MOA
grab a pint- take away Ca"- bites alpha 2 delta subunit of voltage gated calcium channels- reduces influx of calcium nothing to actually do with GABA
Gabapentin (Neurontin) what may worsen adverse effects
myoclonus adverse effects: -Drowsiness, dizziness, tiredness-ataxia and weight gain
Phenytoin (Dilantin) MOA- what is it due to enzymes- specifically what is it due with valproic acid
-inhibitor sodium channel- this is a potent enzyme INDUCER.- competes with valproic acid for protein binding when used together **
phenytoin good for what seizures and worsened what seizures
good -focal- generalized tonic-clonic worsened -myoclonic- absence
pro drug of phenytoin and what is important to remember
fosphenytoin- this can be given for status epilepticus, a 20 mg/kg**Risk for HYPOTENSION AND ARRHYTHMIA. THEREFORE NEEDS EKG MONITORING
phenytoin adverse effects
- gingival hyperplasia- acne, hirsutism- cerebellar atrophy at high doses- toxicity leading to- incoordination -Dysarthria -Nystagmus -diplopia
Lacosamide (Vimpat)Mechanism of action seizure type status
ENHANCES slow inactivation of sodium channel- effective for focal and generalized tonic-clonic seizures- not effective for myoclonic or absence seizures -can be given for IV status dose of 200-400 mg
side effects of lacosamide ( Vimpat)
prolonged PR interval*** -dizziness, nausea, vomiting, diplopia, fatigue
pregabalin (Lyrica) mechanism of action
similar gabapentin-binds to the alpha 2 delta subunit voltage-gated calcium channels -Reduces influx calcium
-pregabalin Lyrica good for what seizures- pregabalin makes what seizures worse
-effective for focal seizures -Worsened generalized myoclonic or absence seizures
adverse effect of pregabalin
-dizziness and somnolence -Increase appetite -Weight gain -Peripheral edema
Cenobamate (Xcopri) MOA
-sodium channel blocker -enhances GABA activity through allosteric modulation of GABA A receptor
Cenobamate- affect on antiepileptics- OCPs
- increase his levels of (VIA INHIBITOR OF CYP2C19)Phenytoin Phenobarbital ClobazamINDUCES CYP3A4 reduces efficacy of OCP
Cenobamate (Xcopri)-what seizures-biggest adverse effect to be aware of
- effective against focal seizures- due to risk of DRESS syndrome must be up titrate slowly Other somnolence, dizziness, fatigue
medication for infantile spasms especially in the setting of tubular sclerosis
Vigabatrin (Sabril)
irreversible inhibitor of GABA transaminase
Vigabatrin
Vigabatrin (Sabril)- adverse effects
- progressive in permanent bilateral concentric visual field constriction (up to 30-40% risk increases with higher daily dose and longer duration therapy )- sedation, fatigue, dizziness, depression, weight gain
what seizures is Cannabidiol (Epidiolex) good for
-Lennox-Gastaut syndrome-Dravet syndrome -tubular sclerosis complex
Cannabidiol (Epidiolex) MOA note: Only available as oral solution
-unknown may enhance GABA through modulation of receptor
Cannabidiol (Epidiolex) interactions
many. •increases N-desmethylclobazam (active metabolite of clobazam)
Cannabidiol (epidiolex) adverse effect
- sedation -decreased appetite-diarrhea-Increased LFT ** esp when using with VPA / clobazam
what monitoring do need for CBD
LFT and bilirubin. Baseline, 1, 3, and 6 months after initiation of treatment
Stiripentol (Diacomit) MOA
-modulation of GABA A receptors -Prevents GABA reuptake
What to consider went starting Stiripentol (DIAcomit)
causes elevation in clobazam and VPAreduced clobazam and valproic on starting this
When to give Stiripentol (diacomit
FDA approved for adjunctive treatment of pts 2 years or older with Dravet syndrome who are taking clobazam
Stiripentol (diacomit) adverse effects
- anorexia- weight loss - Somnolence
Fenfluramine (Fintepla) MOA
-increase his serotonin by disrupting vesicular storage in reversing serotonin transporter functionFen- Fun
Fenfluramine good for what seizures
-Lennox-Gastaut syndrome and Dravet Syndrome the patient is 2 years or older
Fenfluarmine AE
-decreased appetite, weight loss-vascular disease and pulmonary hypertension have not been seen in patients treated for epilepsy** it can only be prescribed under the REMS program and requires echocardiogram at baseline, 6 months during treatment, and 6 months after stopping and treatment
Fenfluramine interactions
If given with Stiripentol and clobazam--> its concentration will increase
what to consider the patient is taking Clobazam
Stiripentol (Diacomit)FDA approved for adjunctive treatment of patients 2 years or older with Dravet syndrome who are currently taking clobazam.
antiepileptic for Lennox-Gastaut syndrome
- Clobazam (onfi)-CBD (Epidiolex)-Rufinamide-Felbamate