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Pharm II > Epilepsy > Flashcards

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
Q

How do the following drugs work? Valproic Acid (Depakene) & Sodium Valproate (Depakote)

A

Both meds work the same way.

Na+ blockade and enhancement of GABAergic transmission

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26
Q

Indications of Valproic Acid (Depakene) & Sodium Valproate (Depakote)

A

Generalized Seizures

myoclonic, tonic, atonic, absence

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27
Q

Metabolism of Valproic Acid

A

hepatic metabolism but doesn’t induce P450

inhibits metabolism of phenobarbital, carbamazepine, ethosuximide

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28
Q

Side effects of Valproic Acid

A

Dose related: N,V, abdominal pain, diarrhea, sedation, tremor, unsteadiness
Non-dose related: acute hepatic failure, acute pancreatitis
Monitor for jaundice and LFTs

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29
Q

How does Ethosuximide (Zarontin) work?

A

Inhibits Calcium channels

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30
Q

Indications for Ethosuximide (Zarontin)

A

DOC for generalized absence seizures

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31
Q

Side effects of Ethosuximide (Zarontin)

A

Dose related- GI, lethargy; HA, dizziness, anxiety

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32
Q

What are the Second Generation AEDs?

A 
Gabapentin (Neurontin)
Oxcarbamazepine (Trileptal)
Tiagapine (Gabitril)
Felbamate (Felbatol)
Lamotrigine (Lamictal)
Zonisamide (Zonegran)
Levetiracetam (Keppra)
Pregabalin (Lyrica)
33
Q

How does Oxcarbazepine (Trileptal) work?

A

Active metabolite blocks NA+ channels

34
Q

Indications of Oxcarbazepine (Trileptal)

A

partial Sz with or without secondary generalization (can be used first line)

35
Q

Name one analog of Carbamazepine

A

Oxcarbazepine (Trileptal) (Demonstrated equal efficacy and fewer side effects when compared with carbamazepine and phenytoin)

36
Q

ADRs of Oxcarbazepine (Trileptal)

A

Dizziness, ataxia, fatigue, GI, hyponatremia (2.5%), rash

NOTE: 30% cross reactivity for rash with CBZ (remember rash for CBZ is steven johnson)

37
Q

What are the benefits of using Oxcarbazepine (Trileptal) rather than Carbamazepine?

A

Benefit!: No PK monitoring; no autoinduction

38
Q

MOA for Gabapentin (Neurontin)

A

Analog of GABA. MOA unknown

39
Q

Indication for Gabapentin (Neurontin)

A

Adjunct to partial and GTC seizures

Treatment of peripheral neuropathy

40
Q

Pharmacokinetics of Gabapentin (Neurontin)

A 
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
Q

Side effects of Gabapentin

A

Side effect profile: Somnolence, dizziness, ataxia, nystagmus

42
Q

How does Tiagabine (Gabitril) work?

A

Competitive inhibitor of GABA transporter in neurons and glia (inhibits re-uptake)

43
Q

Indications for Tiagabine (Gabitril)

A

adjunctive treatment of partial seizures

44
Q

Pharmacokinetics of Tiagabine (Gabitril)

A

Quickly and completely absorbed
Increased clearance in Pediatrics; with enzyme inducers
Serum concentrations unnecessary

45
Q

Side effects of Tiagabine (Gabitril)

A

Dose related: dizziness, fatigue, nervousness, difficulty concentrating

46
Q

How does Lamotrigine (Lamictal) work?

A

Blocks Na+ and Ca++ channels

47
Q

Pharmacokinetics of Lamotrigine (Lamictal)

A

100% oral absorption; metabolized via Phase II (conjugate step in metabolism. Less effect on other drugs (vs phase I-p450))

48
Q

Side effects of Lamotrigine (Lamictal)

A

Rash (10%), confusion, depression, N,V, diplopia, Severe idiosyncratic (skin, blood)

49
Q

Indications for Lamotrigine (Lamictal)

A

GTC, Partial seizures, absence

50
Q

How does Topiramate (Topamax) work?

A

Blocks Na+ channels and binds GABA thus opening Cl- channels

51
Q

Indications for Topiramate (Topamax)

A

treatment for partial and generalized seizures in pediatrics and adults

52
Q

Pharmacokinetics of Topiramate (Topamax)

A

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
Q

ADRs of Topiramate (Topamax)

A

Dose related: drowsiness, parasthesias, psychomotor slowing, weight loss, renal calculi (Maintain adequate fluids to decrease risk of renal calculi)

54
Q

How does Felbamate (Felbtol) work?

A

Blocks Na+ channels, competes for NMDA receptor, prevents AMPA receptor stimulation, blocks Ca++ channels

55
Q

Indications for Felbamate (Felbtol)

A

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
Q

ADRs of Felbamate (Felbtol)

A

Dose related – anorexia, N/V, insomnia, HA

Non-dose related – aplastic anemia, hepatic failure

57
Q

Indications for Levetiracetam (Keppra)

A

treatment of generalized Sz

58
Q

Pharmacokinetics of Levetiracetam (Keppra)

A

Almost completely absorbed
Metabolism not dependent on P450 system
Minimal protein binding
Minimal drug interactions

59
Q

ADRs of Levetiracetam (Keppra)

A

sedation, behavioral abnormalities

60
Q

How does Zonisamide (Zonegran) work?

A

Sulfonamide derivative (don’t use if pt has sulfa allergy); blocks Na+ and Ca++ channels and enhances GABA-receptor function

61
Q

Indications for Zonisamide (Zonegran)

A

adjunctive therapy for partial Sz

62
Q

Pharmacokinetics of Zonisamide (Zonegran)

A

Good oral absorption

Both Renally and hepatically eliminated

63
Q

ADRs of Zonisamide (Zonegran)

A

Dose related: sedation, dizziness, cognitive impairment, nausea
Non-dose related: rash, oligohydrosis, kidney stones (so adivise pt to maintain adequate volume)

64
Q

Indications of Pregabalin (Lyrica)

A

Adjunctive treatment for partial onset Sz
Peripheral neuropathy (also Gabapentin)
Postherpetic neuralgia
Fibromyalgia syndrome

65
Q

ADRs of Pregabalin (Lyrica)

A

dizziness, somnolence, dry mouth, peripheral edema, blurred vision, weight gain

66
Q

When is it ok to discontinue AED medication regime?

A

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
Q

First choice drugs for Status Epilepticus

A

Benzodiazepines
DOA Lorazepam > Diazepam
Respiratory depression

68
Q

2nd line drugs for Status Epilepticus

A

Hydantoins: Fosphenytoin or phenytoin

69
Q

3rd choice for Status Epilepticus

A

Barbituates: Phenobarbital

70
Q

How do Benzodiazepines work

A

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
Q

ADRs for Benzos

A

Infusion rate related arrhythmias and hypotension
Respiratory depression
Impairment of consciousness

72
Q

Lorazepam (Ativan)

A

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
Q

Lorazepam (Ativan) vs Diazepam (Valium)

A

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
Q

Midazolam (Versed)

A

A type of Benzo. Unique bc it can be administered Buccal, intranasal, IM routes.
Give by continuous infusion for refractory SE

75
Q

Hydantoins

A

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
Q

Administration of Phenytoin in the tx of status epilepticus

A

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
Q

Fosphenytoin (Cerebyx)

A

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
Q

Phenobarbital use in status epilepticus

A

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
Q

ADRs of Phenobarbital

A

More CNS and respiratory depression than hydantoins

Contains propylene glycol

Pharm II (1 decks)

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