Epilepsy Medications – Neurology Rite Review – Flashcards

Lamotrigine

Carbamazepine
Lamotrigine
Gabapentin
Pregabalin
Vigabatrin

Phenytoin
Carbamazepine
Lamotrigine
Gabapenin

(Topiramate is safe to use)

Phenobarbital
Phenytoin
Carbamazepine
Oxcarbazepine
Topiramate >200 mg

Gabapentin
Pregabalin
Levetiracetam
Zonisamide
Tiagabine
Topiramate <200 mg

Indication: partial and GTC

Mechanism of action: inhibits voltage-dependent *sodium channels*

Mainly liver metabolism, minimal renal metabolism, 90% albumin bound, low-protein levels make total drug level unreliable, also can be displaced by other drugs, check for free level

Has non-linear kinetics (saturates metabolic pathways)

Idiosyncratic reactions: aplastic anemia, Stevens-johnson syndrome and hepatic failure

AE: thrombocytopenia, lymphadenopathy, *gingival hyperplasia,* acne, coarse facial features, *hirsutism,* purple glove syndrome, *nystagmus,* ataxia, dysarthria, diplopia, nausea, dizziness, drowsiness, folate deficiency, osteoporosis, cerebellar atrophy, SLE-like syndrome

category x: causes fetal hydantin syndrome

Can worsen myoclonic and absence seizures

(target level-current level) x (kg bodyweight x volume of distribution)

Volume of distribution
dilantin: 0.8 L/kg
VPA: 0.2 L/kg

Long−acting barbiturate prototype: used as a sedative and for tonic−clonic seizures.

* Facilitates GABA*−mediated neuronal inhibition (by increasing *duration* of channel opening) and may block excitatory neurotransmitters.

Partial renal clearance that can be increased by urinary alkalinization.

Chronic use leads to induction of liver drug− metabolizing enzymes and *ALA synthase.*

Tox: Sedation, *somnolence,* irritability, depression, Rash, SJS, hepatitis, connective tissue effects

broad-spectrum AED (used in partial, GTC, absence, myoclonic and tonic seizures and infantile spasms

Antagonist of *sodium and T-type calcium channels,* agonist at GABA-A receptor

Mainly liver metabolism, is an *inhibitor,* significantly increases the half-life of lamotrigine (immediately reduce lamotrigine dose)

SE: cognitive and *GI complaints,* increased liver enzymes, *idiosyncratic fatal hepatitis,* *weight gain, obesity* *alopecia*, polycystic ovarian syndrome, acne, menstrual irregularities, *tremor,* pancreatitis, thrombocytopenia

contraindicated in pregnancy: causes neural tube defects

Partial or secondarily generalized tonic-clonic (GTC)

Blocks *sodium channels*

SE: dizziness, vertigo, fatigue, drowsiness, diplopia, nystagmus, headache, nausea, LFT elevation, *hyponatremia*, ataxia, *Stevens-Johnson,* leukopenia, *aplastic anemia,* *agranulocytosis* hepatotoxicity, SIADH

Liver metabolism with renal excretion, auto-inducer (completed after 3-5 weeks), metabolized to 10-11-carbamazepine epoxide (pharmacologically active, causes SEs, measure if toxicity in conjunction with VPA because it inhibits the metabolism of the epoxide)

black box warning in asians for increase chance of SJS/TEN if *HLA-B-1502*

Can worsen myoclonic and absence seizures

GABA-A agonist-activates chloride channel, hyper-polarization of neuronal membrane and decreased excitability

Interacts with 2-delta-subunit of a presynaptic L-type voltage regulated *calcium channel*

Does not inhibit or induce, no drug interactions, renal excretion without any metabolism

AEs: Fatige, sedation, ataxia, weight gain

Can worsen myoclonic epilepsy

Hypertension, hyperglycemia, weight gain, electrolyte abnormalities, infections, avascular necrosis, GI bleed

Broad spectrum drug (partial and generalized, Lennox-Gastaut)

Requires slow titration (to avoid *Stevens-Johnson,* especially if used with VPA)

SE: *SJS*, HA, dizziness

Oral contraceptives and HRT increased clearance and decrease levels of lamotrigine (not the mini-pill)

Pregnancy increased clearance by up to 65% and causes breakthrough seizures (adjust dose)

-binds *glutamate* vesicle protein SV2A, stops the vesicle release

works on all seizure types

AEs: Irritability, Psychosis

MoA: *blocks Na channels;* Antagonist of AMPA/kainate glutamate receptors; inhibits carbonic anhydrase, inc GABA

Broad spectrum drug (partial and generalized, absence and Lennox-Gastaut)

Excreted unchanged in urine

AE’s: Weight loss, word-finding difficulties, cognitive impairment, confusion, impaired memory, paresthesias, dizziness, nervousness, painful angle-closure glaucoma, calcium oxolate kidney stones

inhibits voltage gated Na channels, inhibits thalamic T-type channels; inhibits carbonic anhydrase

AE: Rash, weight loss, somnolence, *oligohydrosis*, hallucination, SJS, renal calcul

Avoid in pts with sulfonamide allergy.

Structural derivate of carbamazepine (10-monohydroxy-carbamazepine), does not undergo oxidation to epoxide, no auto-induction

Less side effects, faster titration possible

irreversibly inhibits GABA breakdown

used in partial seizures

AEs: *Retinal toxicity,* (1/3 suffer permanent loss of peripheral vision), Headache, fatigue, weight gain, nervousness

Adjunct for partial onset seizures age >17

Selective enhancement of slow inactivation of voltage-dependent *sodium channels,* results in inhibition of repetitive neuronal firing and stabilization of hyper excitable neuronal membranes, also interfere with collapsing response mediator protein 2 (CRMP-2)

Eliminated renally, little drug-drug interaction

SE: dizziness, nausea

Adjunct treatment for Lennox-Gastaut age >4
Modulates neuronal sodium channels
Extensive metabolism

AEs: GI effects, fatigue, dizziness, Rash, SJS, leukopenia

GABA reuptake inhibitor

AEs: irritability, anxiety, weakness, Spike-wave stupor

MOA: modulator of GABAA receptors[4][5] and as a blocker of NMDA receptors

AEs: Insomnia, headache, weight loss, nausea; Aplastic anemia, hepatotoxicity, rash, SJS

Specific ligand of alpha-2-delta type 1 and 2 of Ca2+ channel.

used as adjunctive therapy, *lower efficacy*. Can treat chronic pain disorders such as *fibromyalgia and spinal cord injury*

*Weight gain,* edema, Rash, elevated CPK

MOA: fast *Na channel blocker* stabilizing hyperexcited neuronal membranes, inhibiting the repetitive firing and reducin the propagation of synaptic impulses

AEs: Dizziness, GI effects, *hyponatremia;* Rash, SJS
oxcarbazepine

post-anoxic action myoclonus

tx: Clonazepam, sodium valproate, and levetiracetam