Antiepileptics Flashcards
All Old Generation Antiepileptics (List)
Phenytoin (Dilantin) Fosphenytoin (Cerebyx) Carbamazepine (Tegretol) Ethosuxamide (Zarontin) Valproic Acid derivatives: Sodium Valproate (Depakene) and Valproic Acid (Depakote) Phenobarbital (Luminal) Primidone (Mysoline)
GABA
The major inhibitory neurotransmitter
Indication for Phenytoin(Dilantin)
Primary generalized and partial seizures. NOT absence seizures.
Mechanism of Phenytoin(Dilantin)
Blocks Na+ channels associated with depolarization, depolarization and membrane stability.
Also prolongs inactive period of Na+channels to stop the rapid firing of action potentials.
Cardiac effects of Phenytoin (Dilantin) . dose dependent.
Widening of QRS.
Remember, do NOT give Dilantin for TCA overdose as they widen QRS as well.
Phenytoin (Dilantin) routes of administration
Dilantin infatabs- chewable (50mg)
Dilantin suspensions- 30mg/5ml or 125mg/5ml
capsules- 30 mg or 100mg
Injection- 50mg/ml, contains propylene glycol
No IM Injection
Max rate of Phenytoin (Dilantin) IV Infusion
50mg/minute
Prodrug of Phenytoin (Dilantin)
Fosphenytoin ( Cerebyx)
Max infusion 150mg/minute
Benefit of Fosphenytoin (Cerebyx)
no propylene glycol (tachydysrhythmias and hypotension)
can be given IM
Phenytoin (Dilantin) reference range
7-20mg/L
some say 10-20mg/L= measures both bound and the free fraction (1-2mg/L)
free fraction is the “active” form of the drug
Average dose of Phenytoin (Dilantin) adult and peds
Adult maint (oral)=300-400mg/day PO Pedi maint = 4-8mg/kg/day (1-2 divided doses)
Phenytoin (Dilantin) toxicity doses and symptoms
> 20mg/L=nystagmus
30mg/L=ataxia, seizures
40mg/L=lethargy, altered consciousness, coma. must protect airway.
Phenytoin (Dilantin) Side effects
Sedation, gingival hyperplasia, hirsutism, hyperglycemia, osteoporosis, teratogenicity (cat D), DRESS, megaloblastic anemia (due to folate def.)
Phenytoin (Dilantin) is an inducer of:
CYP3A4
Indications for Carbamazepine (Tegretol)
1)partial and secondarily generalized tonic-clonic seizures
2) DOC for trigeminal neuralgia
3) mood stabilizer in bipolar disorder
NOT myoclonic seizures (worsens)
Carbamazepine (Tegretol) Mech of Action
Blocks Na+ channels (similar to phenytoin)
has similar shape and is related to other antidepressants
Carbamazepine (Tegretol) therapeutic range
4-12 mg/L
active metabolite of Tegretol
10,11 epoxide.
causes induction and its own metabolism by inducing CYP3A4
DDI of Tegretol
Inducer of CYP1A2, 2B6, 2C8, 2C9, 2C19, 3A4
decreases Warfarin’s effect
causes oral contraceptive failure
erythromycin inhibits metabolism
pharmacogenetics concern with Tegretol
HLA-B*1502 allele: causes a severe rash (SJS, TEN) win Han Chinese, asian populations, or people from Thailand, India, Singapore, or Malaysia
Life threatening skin reaction
Side Effects of Carbamazepine (Tegretol)
HLA-B*1502 allele skin reaction Leukopenia - caution with BMS its Aplastic Anemia and agranulocytosis - Black box Hyponatremia -stimulates release of ADH Drowsiness fatigue
Indications for Oxcarbamazepine (Trileptal)
initial or adjunct therapy for partial seizures
not ‘approved’ for bipolar but is often used as a mood stabilizer when CBZ has adverse SE
available routes/formulations of Trileptal
Tablet= 150, 300 or 600 mg as either IR or XR
Suspension=300mg/5ml (contains ethanol) - don’t give with Antabuse or flagyl*
IR give without regard to food
XR should be taken on empty stomach
Trileptal pharmacokinetics and DDI
Strong inducer of CYP3A4 and UDP
inhibits CYP2C19
lowers Oral contraceptives
increases levels of phenobarbital and phenytoin
Oxcarbamazepine (Trileptal) Side Effects
HA, dizziness, nystagmus, blurred vision, n/v, rash, hyponatremia
less than CBZ (some cross-sensitivity)
Eslicarbazepine (Aptiom) indications
usually adjunct therapy
partial onset seizures
Eslicarbazepine (aptiom) dosing
400 mg tablet PO
max 1200mg/day
eslicarbazepine (aptiom) metabolism
rapid metabolism by first pass effect into eslicarbazepine and oxcarbazepine
Valproic acid derivatives indications
Complex partial seizures (mono or adjunct) status epilepticus absence seizures bipolar disorder migraine prophylaxis
Valproic acid formulations
Valproic acid (Depakene, Stavzor) caps/syrup Depakote (enteric coated tabs)-often preferred
Valproic acid mechanism of action
partial Na+channel blocker
increases GABA levels by inhibiting GABA degradation
Valproic acid reference range
50-125 mg/mL
toxicity starts at 150-200
Valproic acid SE
GI (common): n/v/d dyspepsia
weight gain, hepatotoxicity, pancreatitis, tremors, dose dependent thrombocytopenia, teratogenicity due to folate deficiencies
*hyperammonemia (NH3+) - consider L-carnitine therapy
if asymptommatic=100mg/kg/day in 4 doses PO
if symptomatic = 100mg/kg IV (max 6g) over 30 min
then paint of 15mg/kg q4 hours over 10-30 min
Valproic acid DDI
Lamotrigine (lamictal) Phenytoin (dilantin) Phenobarbital (Luminal) CBZ ethosuximide (zarontin) AZT (zidarvidine)
ethosuximide (Zarontin) indications
ONLY pure absence seizures
not used with atypical absence seizures
ethosuximide (Zarontin) reference range
60-100mcg/mL
ethosuximide (Zarontin) SE
GI Gastritis (primary) fatigue, HA, neuropsychotic behavior Rash (SJS) Leukopenia (check CBC) lupus-like syndrome
phenobarbital (Luminal) indications
as an alternative for partial or generalized tonic-clonic seizures
*worsens absence seizures
usually 2nd line.
may be seen in pregnancy
phenobarbital (Luminal) MOA
enhances GABA mediated inhibition by increasing Cl Channel openings: hyperpolarizes the neuron
Phenobarbital (Luminal) dosing
Peds 2-8mg/kg/day in 1-2 doses
adults 90-180 mg once or 2 doses
Phenobarbital (Luminal) reference range
desired 15-40mg/L
Toxic: >50mg/L= resp depression
Clinical issues with Phenobarbital (Luminal)
inducer of CYP450 and UGT enzymes: DI
Sedation as main SE
can develop tolerance to phenobarb
Primidone (Mysoline) indications
Same as phenobarbital
alternative for partial and generalized tonic clonic seizures
Primidone (mysoline) metabolism
metabolized to PEMA (Phenylethylmalonamide) and Phenobarbital
Primidone (Mysoline) dosing
adults: 750-1000 mg/day in 3-4 div doses (Max 2 g)
Peds: 10-25 mg/kg/d in 2-3 div doses
also give folic acid supplement
Primidone (Mysoline) SE
CNS depression Sedation Confusion Suicidal ideation *megaloblastic anemia: due to lowering of RBC and CSF folate levels
avoid in pregnancy
