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Epilepsy Flashcards

1
Q

Drugs That Cause Seizures

A 
Antimicrobials
Anesthetics and analgesics
Immunosuppressants
Psychotropics
Radiographic contrast agents
Theophylline
Sedative hypnotic drug withdrawal
Drugs of abuse
Flumazenil
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2
Q

First line drugs of choice for partial seizures (

Carb PLOT)

A 
carbamazepine
phenytoin
lamotrigine
oxcarbazepine
topiramate
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3
Q

Second line drug of choice for partial seizures

A 
gabapentin
levetiracetam
phenobarbital
pregabalin
primidone
tiagabine
valproic acid
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4
Q

Drugs of choice for generalized absence seizures

A

First line: ethosuximide, Lamotrigine, Valproic Acid

Second line: Clonazepam

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5
Q

Drugs of choice for generalized myoclonic, atonic seizures

A

First line: Valproic acid, lamotrigine

Second line: clonazepam, topiramate

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6
Q

Drugs of choice for generalized Tonic-clonic seizures

A

first line: valproic acid, carbamazepine, oxcarbazepine, lamotrigine

second line: levetiracetam, phenobarbital, phenytoin, topiramate

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7
Q

Phenytoin (Dilantin) MOA

A

Blocks voltage-gated Na+ channels —> reduces propagation of abnormal impulses in brain

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8
Q

Phenytoin (Dilantin) Indications

A

Simple and complex partial Sz
Generalized tonic-clonic Sz
Status epilepticus

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9
Q

Phenytoin (Dilantin) pharmacokinetics

A

Metabolism by P450 system
Potent non-specific inducer of many drug metabolizing enzymes (other drugs wont work as well bc theyre metabolized)
Highly protein bound (not good for other drugs)
Non-linear kinetics- hard to predict whats happening
Requires close therapeutic monitoring
Therapeutic range 10-20 mg/L

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10
Q

Phenytoin (Dilantin) administration

A

Enteral feeding reduces oral absorption
Oral suspension must be shaken vigorously
Intravenous formulation (some issues)
Basic pH…phlebitis and extravasation are concerns (can cause pain when its infused)

Hypotension: maximum infusion rate = 50mg/min (if you stay below 50, pt shouldn’t experience hypotension. Monitor for this)
No IM injection

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11
Q

What are the drugs that phenytoin induces?

A

carbamazepine, OCP, doxycycline, quinidine, cyclosporin, methadone, levodopa

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12
Q

What are the drugs that are inhibitors of phenytoin?

A

chloramphenicol, cimetidine, sulfonamide, isoniazid

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13
Q

ADRs of phenytoin

A

Dose related: nystagmus, ataxia, drowsiness, cognitive impairment
Non-dose related: gingival hyperplasia, hirsutism, acne, rash, hepatotoxicity

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14
Q

Phenytoin relationship of toxicity to serum concentrations

A

> 20 mcg/ml – nystagmus
30 mcg/ml – ataxia
40 mcg/ml – mental status changes (coma)

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15
Q

Which drug is Fetal Hydantoin Syndrome associated with?

A

Phenytoin. Very teratogenic.
Cleft lip and palate
Congenital heart disease
Slowed growth and mental deficiency

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16
Q

How does Carbamazepine (Tegretol) work?

A

Blocks Na+ channels

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17
Q

Indications of Carbamazepine (Tegretol)

A

first line for treatment of simple partial, complex partial, and generalized tonic-clonic

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18
Q

Metabolism of Carbamazepine (Tegretol)

A

Metabolism through autoinduction*
First 20-30 days of treatment
Autoinduction is dose dependent
After autoinduction is complete, steady state concentrations achieved after 3 days

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19
Q

Is Carbamazepine an inducer or inhibitor of other drugs?

A

Potent non-specific inducer of many drug metabolizing enzymes and transporters
Metabolism mostly through CYP 3A4

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20
Q

ADRs of Carbamazepine

A

Dose related: vertigo, ataxia, diplopia, drowsiness, nausea
CNS side effects: HA, paresthesias, confusion, psychosis
Non-specific: SIADH (makes you not pee), leukopenia, thrombocytopenia, Stevens-Johnson Syndrome

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21
Q

Indications of Phenobarbital (Luminal)

A

Generalized tonic clonic
Partial Sz
Neonatal Sz
Febrile Sz

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22
Q

Side effects of Phenobarbital (Luminal)

A

sedation, irritability, slowed thinking, ataxia, hyperactivity, rash

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23
Q

What is unique about Phenobarbital’s pharmacokinetics?

A

Half-life: 96 hours. Means huge amt of time before you reach steady state.
Time to steady state: 20-30 days
Metabolized by P450 system (potential for drug interactions)

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24
Q

Indications of Primidone (Mysoline)

A

Alternative choice in partial SZ and tonic-clonic SZ
Efficacy from metabolites (prodrug). Can’t pick. Pt will get both metabolites
Phenobarbital (tonic-clonic SZ and simple partial SZ)
Phenyethylmalonamide (complex partial SZ)
Well-absorbed orally (easier to get into the body); poor protein binding; same adverse effects as phenobarbital

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25
How do the following drugs work? Valproic Acid (Depakene) & Sodium Valproate (Depakote)
Both meds work the same way. | Na+ blockade and enhancement of GABAergic transmission
26
Indications of Valproic Acid (Depakene) & Sodium Valproate (Depakote)
Generalized Seizures | myoclonic, tonic, atonic, absence
27
Metabolism of Valproic Acid
hepatic metabolism but doesn’t induce P450 | inhibits metabolism of phenobarbital, carbamazepine, ethosuximide
28
Side effects of Valproic Acid
Dose related: N,V, abdominal pain, diarrhea, sedation, tremor, unsteadiness Non-dose related: acute hepatic failure, acute pancreatitis Monitor for jaundice and LFTs
29
How does Ethosuximide (Zarontin) work?
Inhibits Calcium channels
30
Indications for Ethosuximide (Zarontin)
DOC for generalized absence seizures
31
Side effects of Ethosuximide (Zarontin)
Dose related- GI, lethargy; HA, dizziness, anxiety
32
What are the Second Generation AEDs?
``` Gabapentin (Neurontin) Oxcarbamazepine (Trileptal) Tiagapine (Gabitril) Felbamate (Felbatol) Lamotrigine (Lamictal) Zonisamide (Zonegran) Levetiracetam (Keppra) Pregabalin (Lyrica) ```
33
How does Oxcarbazepine (Trileptal) work?
Active metabolite blocks NA+ channels
34
Indications of Oxcarbazepine (Trileptal)
partial Sz with or without secondary generalization (can be used first line)
35
Name one analog of Carbamazepine
Oxcarbazepine (Trileptal) (Demonstrated equal efficacy and fewer side effects when compared with carbamazepine and phenytoin)
36
ADRs of Oxcarbazepine (Trileptal)
Dizziness, ataxia, fatigue, GI, hyponatremia (2.5%), rash | NOTE: 30% cross reactivity for rash with CBZ (remember rash for CBZ is steven johnson)
37
What are the benefits of using Oxcarbazepine (Trileptal) rather than Carbamazepine?
Benefit!: No PK monitoring; no autoinduction
38
MOA for Gabapentin (Neurontin)
Analog of GABA. MOA unknown
39
Indication for Gabapentin (Neurontin)
Adjunct to partial and GTC seizures | Treatment of peripheral neuropathy
40
Pharmacokinetics of Gabapentin (Neurontin)
``` Favorable PK profile: dose-dependent oral absorption (means easy to predict, easy to dose) not protein bound excreted unchanged via kidneys no serum level monitoring ```
41
Side effects of Gabapentin
Side effect profile: Somnolence, dizziness, ataxia, nystagmus
42
How does Tiagabine (Gabitril) work?
Competitive inhibitor of GABA transporter in neurons and glia (inhibits re-uptake)
43
Indications for Tiagabine (Gabitril)
adjunctive treatment of partial seizures
44
Pharmacokinetics of Tiagabine (Gabitril)
Quickly and completely absorbed Increased clearance in Pediatrics; with enzyme inducers Serum concentrations unnecessary
45
Side effects of Tiagabine (Gabitril)
Dose related: dizziness, fatigue, nervousness, difficulty concentrating
46
How does Lamotrigine (Lamictal) work?
Blocks Na+ and Ca++ channels
47
Pharmacokinetics of Lamotrigine (Lamictal)
100% oral absorption; metabolized via Phase II (conjugate step in metabolism. Less effect on other drugs (vs phase I-p450))
48
Side effects of Lamotrigine (Lamictal)
Rash (10%), confusion, depression, N,V, diplopia, Severe idiosyncratic (skin, blood)
49
Indications for Lamotrigine (Lamictal)
GTC, Partial seizures, absence
50
How does Topiramate (Topamax) work?
Blocks Na+ channels and binds GABA thus opening Cl- channels
51
Indications for Topiramate (Topamax)
treatment for partial and generalized seizures in pediatrics and adults
52
Pharmacokinetics of Topiramate (Topamax)
2C19 substrate and inhibitor p450 70% renal elimination- dose adj in pt w/ renal compromise 1st order kinetics- easy to dose Clearance increased with enzyme inducers
53
ADRs of Topiramate (Topamax)
Dose related: drowsiness, parasthesias, psychomotor slowing, weight loss, renal calculi (Maintain adequate fluids to decrease risk of renal calculi)
54
How does Felbamate (Felbtol) work?
Blocks Na+ channels, competes for NMDA receptor, prevents AMPA receptor stimulation, blocks Ca++ channels
55
Indications for Felbamate (Felbtol)
Partial Sz and Lennox-Gastaut syndrome Use restricted to refractory Lennox-Gastaut syndrome Active metabolite covalently (irriversibly) binds liver and bone marrow proteins and DNA Aplastic anemia and liver failure
56
ADRs of Felbamate (Felbtol)
Dose related – anorexia, N/V, insomnia, HA | Non-dose related – aplastic anemia, hepatic failure
57
Indications for Levetiracetam (Keppra)
treatment of generalized Sz
58
Pharmacokinetics of Levetiracetam (Keppra)
Almost completely absorbed Metabolism not dependent on P450 system Minimal protein binding Minimal drug interactions
59
ADRs of Levetiracetam (Keppra)
sedation, behavioral abnormalities
60
How does Zonisamide (Zonegran) work?
Sulfonamide derivative (don’t use if pt has sulfa allergy); blocks Na+ and Ca++ channels and enhances GABA-receptor function
61
Indications for Zonisamide (Zonegran)
adjunctive therapy for partial Sz
62
Pharmacokinetics of Zonisamide (Zonegran)
Good oral absorption | Both Renally and hepatically eliminated
63
ADRs of Zonisamide (Zonegran)
Dose related: sedation, dizziness, cognitive impairment, nausea Non-dose related: rash, oligohydrosis, kidney stones (so adivise pt to maintain adequate volume)
64
Indications of Pregabalin (Lyrica)
Adjunctive treatment for partial onset Sz Peripheral neuropathy (also Gabapentin) Postherpetic neuralgia Fibromyalgia syndrome
65
ADRs of Pregabalin (Lyrica)
dizziness, somnolence, dry mouth, peripheral edema, blurred vision, weight gain
66
When is it ok to discontinue AED medication regime?
Seizure free for 2-5 years an AED Pt should have single type of partial or primarily generalized tonic-clonic Sz Pt should have a normal neuro-exam and normal IQ Patient’s EEG should have normalized with AED treatment
67
First choice drugs for Status Epilepticus
Benzodiazepines DOA Lorazepam > Diazepam Respiratory depression
68
2nd line drugs for Status Epilepticus
Hydantoins: Fosphenytoin or phenytoin
69
3rd choice for Status Epilepticus
Barbituates: Phenobarbital
70
How do Benzodiazepines work
Act as positive allosteric modulators (bind at separate site) by enhancing channel gating in presence of GABA. 1st line of therapy to terminate sz in status epilepticus
71
ADRs for Benzos
Infusion rate related arrhythmias and hypotension Respiratory depression Impairment of consciousness
72
Lorazepam (Ativan)
DOC for patient with IV access Dose 0.1 mg/kg over 30 sec. May repeat q5 minutes (max dose usually 4mg) Onset of action: 3-5 minutes Can cause vein irritation…dilute dose with equal volume D5W, NS, SWI
73
Lorazepam (Ativan) vs Diazepam (Valium)
Lorazepam preferred over diazepam secondary to duration of action Diazepam highly lipophilic and quickly redistributes out of brain to other fat stores in body Diazepam DOA: 15 min to 2 hr Lorazepam DOA: 12-24 hr
74
Midazolam (Versed)
A type of Benzo. Unique bc it can be administered Buccal, intranasal, IM routes. Give by continuous infusion for refractory SE
75
Hydantoins
fosphenytoin and phenytoin Second-line (loading dose) if Sz continue after 2-3 doses of Benzos Less CNS and respiratory depression than benzodiazepines and barbituates
76
Administration of Phenytoin in the tx of status epilepticus
Erratic absorption and pain with IM injection Dilute to <5 mg/ml with NS Contains propylene glycol (antifreeze) Arrhythmias, hypotension, metabolic acidosis with repeated doses
77
Fosphenytoin (Cerebyx)
H2O soluble prodrug of phenytoin converted by plasma esterases. Preferred over phenytoin. Doses expressed as phenytoin equivalents (PE) Compatible with most IV solutions with less phlebitis Doesn’t contain propylene glycol!! Paresthesias and pruritis more frequent than with phenytoin
78
Phenobarbital use in status epilepticus
3rd line agent: If Sz persists despite 2-3 doses of benzos and loading dose of hydantoin 2nd line agent: If Sz continues after 2-3 doses of benzos and hydantoins contraindicated Pediatrics
79
ADRs of Phenobarbital
More CNS and respiratory depression than hydantoins | Contains propylene glycol

Pharm II (1 decks)

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