Antiepiliptic Drugs

Diagnosis:
Drug Selection (mono therapy first)
-trial period
-monitoring drug levels (adherence, adverse affects)
-tritrate down to lowest effective dose
COMPLIANCE!!- abrupt discontinuation can cause seizures
**Narrow Therapeutic Index Drugs
-Levels may

Antiepileptic Drugs:
Traditional vs. Newer Generation

Traditional-
-used for decades, well documented and studied
-higher risk for developing fetus
-hepatic enzyme involvement (drug-drug)
-more sedative, adverse effects
Newer-
-may have less risk for developing fetus
-less drug-drug interactions

Pheytoin and Fosphenytoin Class

Traditional Antiepileptics
Hydantoins

Pheytoin and Fosphenytoin Pharmacology

selective inhibition of sodium channels

Pheytoin and Fosphenytoin Adverse Effects

gingival hyperplasia
Stevens Johnson Syndrome
Toxic Epidermal Necrolysis
teratogenic- pregnancy category D
cleft lip/palates
Nystagmus
ataxia
diplopia
drowsiness
sedation
cardiac dysrhythmias
hypotension
Hirutism
Skin Rash*
osteoporosis- long-term use

Pheytoin and Fosphenytoin Pharmacokinetics

non-linear, saturable kinetics
narrow therapeutic index (10-20 mcg/mL)
enzyme inducer (oral contraceptives, Warfarin)

Pheytoin and Fosphenytoin Used to Treat

All types of Seizures
-drug of choice in adults and older children
status epilepticus
no longer used for cardiac dysrhythmias

Pheytoin and Fosphenytoin Boxed Warning

Too rapid infusion can cause dysrhythmias/ hypotension

Enzyme Inducers

PS PORCS
Phenytoin
smoking
phenobarbital
oxcarbazepine
rifampin
carbamazepine
St. johns wort

Enzyme Inhibitors

PACMAN loves Grapefruit Juice
Protease Inhibitors
Azole antifungals
Cimetidine
Macrolides
Amiodarone
Non-DHP calcium channel blockers
Grapefruit Juice

Phenobarbital Class

Traditional Antiepileptics
Barbiturates

Phenobarbital Pharmacology

amplifies the actions of GABA and directly mimic GABA

Phenobarbital Adverse Effects

dose dependent
respiratory depression
fetal abnormalities
lower BP and HR
toxic doses can cause serious hypotension and shock
Physical dependence/tolerance
-alcohol, benzodiazepines, barbiturates
-tolerance to therapeutic effect, not respiratory depressio

Phenobarbital Used to Treat

Seizures
sedatives
off label alcohol withdrawal
abuse potential, controlled substance
overdose- abusers or intended suicide

Phenobarbital Monitoring

Watch respiratory rate
heart rate
blood pressure

Phenobarbital Drug-Drug Interactions

CYP450 inducer

Carbamazepine Class

Traditional Antiepileptics
Iminostilbenes

Carbamazepine Pharmacology

Blockade of Na+

Carbamazepine Adverse Effects

severe rash- genetic testing
bone marrow suppression- aplastic anemia and agranulocytosis
visual effects- nystagmus, blurred vision, diplopia
ataxia, vertigo, unsteadiness
headache

Carbamazepine Pharmacokinetics

Enzyme AUTO inducer
narrow therapeutic index

Carbamazepine Used to Treat

Seizures
Bipolar Disorder
Trigeminal and glossopharyngeal neuralgias

Carbamazepine Boxed Warning

Bone marrow suppression that leads to hematological effects- aplastic anemia and agranulocytosis
Severe rash
Teratogenic*-Pregnancy Category D

Carbamazepine Drug-Drug Interactions

Oral Contraceptives, Warfarin
AVOID grapefruit juice

Valproic Acid Class
(Devalproex sodium)
(Valproate)

Traditional Antiepileptics

Valproic Acid Pharmacology

Blockage of Na+, Ca++ channels and may potentiate effects of GABA

Valproic Acid Adverse Effects

Pacreatitis
Fetal Harm- Teratogenic Pregnancy Category D** 4x higher risk than other AEDs
Neural Tube Defects
spina bifida
cleft palate
several more
Hepatoxicity
GI- N/V

Valproic Acid Used To Treat

Epilepsy
all types of seizures
bipolar disorder
migraine prevention
lots of off label uses

Valproic Acid Boxed Warning

Hepatotoxicity
Pancreatitis
Fetal Harm
Patient with mitochondrial disease increased risk for liver failure

Newer Antiepileptic Considerations

Enzyme Induction
Adverse Effects
Pregnancy
Monitoring Levels

Lamotrigine Class

Newer Antiepileptics

Lamotrigine Pharmacology

inhibits release of glutamate and inhibits voltage-sensitive sodium channels, which stabilizes neuronal membrances

Lamotrigine Adverse Effects

Skin Rash
Pregnancy Category C
-cleft palate/lip
N/V
diplopia
blurred vision
higher risk for suicide ideations compared to other AEDs

Lamotrigine Used To Treat

Epilepsy
Bipolar Disorders

Topiramate Class

New Antiepileptics

Topiramate Pharmacology

blocks neuronal voltage-dependent sodium channels, enhances GABA activity, antagonizes glutamate receptors

Topiramate Adverse Effects

Weight loss/ anorexia
somnolence, dizziness, diplopia
Pregnancy- cleft palate/lip

Topiramate Used to Treat

Epilepsy
Migraines/ Cluster Headaches
Off label: weight loss

Gabapentin Class

Newer Antiepileptics

Gabapentin Pharmacology

structurally related to GABA but does NOT bind to GABA receptors
MOA is complex
believe to delay release of excitatory neurotransmitters

Gabapentin Adverse Effects

Peripheral edema
somnolence, dizziness
-caution with CNS depression

Gabapentin Used to Treat

Epilepsy
post herpetic neuralgia
off label:
-diabetic neuropathy
-hot flashes
-post-op pain
-restless leg syndrome
-social anxiety

Levetiracetam Class

Newer Antiepileptics

Levetiracetam Pharmacology

Unknown

Levetiracetam Adverse Effects

Behavioral Problems
Increased BP
CNS depression

Levetiracetam Pharmacokinetics

Linear
IV to PO 1:1
Loading Doses

Lacosamide Class

New Antiepileptic

Lacosamide Pharmacology

stabilizes hyper excitable neuronal membranes and inhibits repetitive neuronal firing by enhancing the slow inactivation of sodium channels

Lacosamide Adverse Effects

1%- euphoria
CNS sedation
Prolong PR interval
Ophthalmic: diplopia, nystagmus

Lacosamide Pharmacokinetics

IV to PO 1:1