Anticonvulsants PDF

**Name/Type** **MOA** **Indications** **SE** **Considerations** **Anti-Epileptic** Phenytoin (Dilantin) oral/IV Fosphenytion-prodrug of Phenytoin, doesn\'t contain propylene glycol and is not approved in oral route Blocks Na+ channels associated with depolarization, repolarization, and mem...

**Name/Type** **MOA** **Indications** **SE** **Considerations** **Anti-Epileptic** Phenytoin (Dilantin) oral/IV Fosphenytion-prodrug of Phenytoin, doesn\'t contain propylene glycol and is not approved in oral route Blocks Na+ channels associated with depolarization, repolarization, and membrane stability. Works on voltage channels -inhibits and stabilizes electrical discharges in the motor cortex of the brain -Hydantion Primary generalized and partial seizure -First line Treatment for tonic-clonic or partial complex seizures, Most commonly used -\>20mg/L- Nystagmus -\>30mg/l- Ataxia, increased seizure -\>40mg/l-lethary, altered LOC, coma -Gingival hyperplasia -Hirsutism -Coarsening face features -hyperglycemia -hematologic effects -Osteoporosis -Rash, DRESS Megaloblastic anemia -Teratogenic ARthralgia -lymphadenopathy -agitation -HA -hypotension -tachycardia -arrhythmia GI upset -known to worsen absence seizure -therapeutic drug level: 10-20mg/l -Wait to check levels until Css: Low levels- 5-7 days High level-4-6 wks Dose adjustments: -Cp \12-increase by 30mg/day or less -0.74mg/kg will increase level by 1ug/ml -monitor for albumin and uremia, BUN which can increase free fraction and there is a correction factor-can cause lab level misinterpretation -Hepatitis- hypersensitivity reaction Drug interactions: allopurinol, diazepam, ETOH, antacids, calcium, Barbs, CBZ, corticosteroids, Dig, Doxy, Haldol, Oral contraceptive, Dopa, Lasix Carbamazepime (Tegretol) Blocks Na+ channles Partial agonist of adenosine A2A/A2B receptors **-**partial and secondary generalized tonic-clonic seizures -Trigeminal neuralgia -Mood stabilizer for bipolar **-**HLA-B1502 allele genetic morphism: Severe rash, Steven-Johnsons(SJS), Toxic epidermal necrolysis(TEN) (Asian descent, Han Chinese, India, Singapore, Malaysia, Thailand -Leukopenia -Aplastic anemia -Hyponatremia(stimulates release of ADH Drowsiness -fatigue -Nystagmus **-**Therapeutic range 4-12mg/l **-**can worsen absence or myoclonic seizures -hepatic elimination -auto-induction reaches max in 2-4 weeks -Decreases effects of Warfarin -Oral contraceptive failure -Erythromycin inhibits metabolism -phenytoin can decrease plasma levels of CBZ Oxcarbazepine (Trileptal, Oxtellar) Inhibit voltage-sensitive Na+ channels and modulate activity of volatage-activated calcium channels Initial of Adjunct therapy for partial seizures Off label Bipolar -fewer SE than CBZ but can have some cross reactivity -HA -Dizzy -Nystagmus -Blurry vision -N/V -rash -hyponatremia -significantly lowers oral contraceptives and increases levels of Phenytoin and Phenobarb -Preg Cat C, Lactation risk Eslicarbazepine (Aptiom) Inhibition of voltage gated Na+ channels Partial onselt seizures Dizzy Drowsy Sedation Hyponatremia diplopia -pregnancy cat C Valproic Acid (Depakene, Depakote) Partially blocks Na+ currents, may increase GABA level and its effects by inhibiting the degradation of GABA by inhibiting GABA-T enzyme in the brain, may also influence glutamic acid decarboxylase -Complex partial seizures -Status epilepticus -Absence seizures -Bipolar d/o -Migraine prophy GI N/V/D Weight gain Hepatotoxicity Pancreatitis Tremors Thrombocytopenia Teratogenicity d/t folate depletion Hyperammonemia that can lead to encephalopathy -Drug interactions: Lamotrigine Phenytoin Phenobarb CBZ Ethosuximide AZT -Preg risk D-neural tube defects, lactation risk Ethosuximide (Zarontin) Primarily blocks thalamic(t-type) Ca++ channels. Inhibits NADPH-linked aldehyde reductase necessary for formation of gamma-hydroxybutyrate. Absence(Petit mal) seizures only -GI Fatigue -HA -Psychotic behavior -Rash (SJS) -Leukopenia -Lupis like syndrome -reference range- 60-100mcg/ml (may go up to 125mcg/ml) -ok in children-weight based dosing -Check CBC periodicly Phenobarbital (Luminal) Barbituate Enhances GABA-meidated inhibition via increasing Cl- channels opening -decreases glutamate mediated excitation on the AMPA receptor -at higher concentrations, blocks Ca++ currents Alternative for partial and generalized tonic-clonic seizures -Typically used as 2nd line may be preferred in pregnant women -avoid in absence seizures(could worsen) -sedation -develope tolerance Reference range: 15-40mg/L Toxic \>50mg/L -pregnancy cat B/D depending on manufacturer -ok in Peds Primidone (Mysoline) Barbituate Unknown, but anticonvulsant effects are thought to be due to the parent compound, primidone, as well as its two active metabolites, phenobarbital and phenylethylmalonamide (PEMA) whose actions may be synergistic. Alternative for partial and generalized tonic-clonic seizures -Typically used as 2nd line may be preferred in pregnant women -avoid in absence seizures(could worsen) CNS depression Sedation Confusion SI Megaloblastic anemia Monitor Phenobarb level instead of Primidone level -reference range for Primidone is 8-12ug/ml but then also have phenobarb levels 15-30ug/ml -required renal dose adjustment -Avoid in pregnancy, lowers folate and crosses placenta Lamotrigine Blocks voltage-sensitive Na+ channels and inhibits glutamate and aspartate -partial seizures -primary generalized tonic-clonic seizures -seizures associated with LGS(Lennox-Gastault Syndrome) Nausea Diplopia Ataxia Rash (SJS) peds at risk -kids \>2 years old -interacts with Valporate and CBZ Gabapentin (neurontin) Binds to amino acid carrier protein and elevates GABA levels Also binds to subunits on the Ca++ voltage gated channels Partial seizures Post-herpatic neuralgia PN RLS Post-op pain Hot flashes Sedation Fatigue Dizzy ataxia -renal adjust Pregabalin (lyrica) gamma-aminobutyric acid (GABA) analog that strongly binds to the alpha(2)-delta site (a subunit of voltage-gated calcium channels) in CNS tissues. Binding to the alpha(2)-delta subunit may be involved in pregabalin\'s effects on neuropathic pain and seizure control. reduces the Ca++ dependent release of pro-nociceptive neurotransmitters, possibly by modulation of calcium channel function. Partial onset seizure(adjunct) Pain assoicuated with PN, Post-herpatic neuropathy FM -edema -sedation -dizzy -blurred vision -weight gain -renal adjust Felbamate (Felbatol) Antagonist to the glycine receptor site on the NMDA receptor, glutamate, and Na+ channels Lennoz-Gastault but not first line -aplastic anemia -N/V Tiagabine (Gabitril) Thought to enhance the activity of GABA by an inhibition of neuronal uptake Parital Seizures -dizzy -drowsy -trouble focusing -weakness Topiramate Inhibits Na+ channels, enhance GABA, antagonize glutamate receptors Epilepsy Migraine Prophy Essential tremors Cluster HA prophy Weight loss Ataxia Impaired concentration Acute angle closed Glaucoma Met acidosis r/t reduction in bicarb Nephroliasis Hyperammoniemia -Pregnancy cat D-risk of Cleft lip -Drug interactions: Phenytoin, ethinylestradiol, CBZ, carbonic acid inhibitores Lacosamide dual mode of action by controlling neuronal hyperexcitability via selective Na+ channel slow inactivation, and binding to collapsin response mediator protein-2 (CRMP-2) which is part of the signal transduction cascade of neurotropic factors Adjunt therapy for partial-onset seizures in epilesy ages \>17 -PR interval prolongation -AV blocks -dysrhythmias -SI -Dizzy -atazia DRESS(drug reaction of eosinophilia and system symptoms Max dose of 300mg daily if renal or heaptic failure -pregnancy cat C Levetiracetam (Keppra) -Inhibits voltage dependent N type Ca++ channels -Facilitates GABA-ergic inhibitory transmission by displacing neg moduclators -reduction of the delayed rectifier K+ current -binds to synaptic vesicle protein 2A ligand that affects neurotransmitter release Partial seizures Tonic-clonic seizures Myoclonic Status epilepticus -Behvior problems Weakness -n/v -HA No reference range No drug levels required No drug interactions Brivaracetam -analogue if Keppra -binds to synaptic vesicle protein 2A ligand that affects neurotransmitter release Partial seizures -drowsiness -dizzy -fatigue -N/V \>16 yo Vigabatrin (Sabril) Irreversible inhibitor of GABA-T which is responsible for the metabolism of GABA Adjunct in refractory partial seizures -monotherapy for infactile spasms \- -retina toxicity -intramyelinic edema in children \