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Med > PHARMACOLOGY ANTISEIZURE > Flashcards

PHARMACOLOGY ANTISEIZURE Flashcards

1
Q

a severe form of epilepsy, usually beginning @ childhood and is characterized by cognitive impairment; can suffer from multiple types of seizures

A

Lennox-Gastaut Syndrome

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2
Q

characterized by an
abnormal interictal high-amplitude slow waves, and EEG
will yield multifocal asynchronous spikes

A

Infantile Spasms s/ hypsarrhythmia:

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3
Q

continuous seizures; goal is to rapidly
terminate the behavioral and electrical seizure activity
because the longer episode untreated → more difficult to
control → higher risk for permanent brain damage (vessels constricted during seizures → brain hypoxia)

A

Status Epilepticus

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4
Q

(effective for newly diagnosed absence epilepsy, but not yet approved for said indication

A

Lamotrigine

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5
Q

CONVENTIONAL ANTISEIZURE

Focal Aware

A

Carbamazepine
Phenytoin

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6
Q

CONVENTIONAL ANTISEIZURE

Focal Aware w/ Impaired Awareness

A

Valproate

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7
Q

CONVENTIONAL ANTISEIZURE

Focal to Bilateral Tonic-Clonic

A

Carbamazepine
Phenytoin
Valproate
Phenobarbital
Primidone

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8
Q

RECENTLY DEVELOPED ANTISEIZURES

Focal Aware

Focal w/ Impaired
Awareness

Focal to Bilateral Tonic-Clonic

A

Brivaracetam
Eslicarbazepine
Ezogabine
Gapantin
Lacosamide
Lamotrigine
Levetiracetam
Perampanel
Rufinamide
Tiagabine
Topiramate
Zonisamide

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9
Q

CONVENTIONAL ANTISEIZURE

Generalized
Absence

A

Ethosuximide
Valproate
Clonazepam

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10
Q

CONVENTIONAL ANTISEIZURE

Generalized
Myoclonic

A

Valproate
Clonazepam

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11
Q

CONVENTIONAL ANTISEIZURE

Generalized
Tonic-Clonic

A

Carbamazepine
Phenobarbital
Phenytoin
Primidone (not first line drug)
Valproate

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12
Q

RECENTLY DEVELOPED ANTISEIZURES

Generalized
Absence

A

Lamotrigine

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13
Q

RECENTLY DEVELOPED ANTISEIZURES

Generalized
Myoclonic

A

Levetiracetam

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14
Q

RECENTLY DEVELOPED ANTISEIZURES

Generalized
Tonic-Clonic

A

Lamotrigine
Levetiracetam
Topiramate

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15
Q

CONVENTIONAL ANTISEIZURE

Infantile spasms w/
hypsarrhythmia

A

Vigabatrin

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16
Q

CONVENTIONAL ANTISEIZURE

Lennox-Gastaut
Syndrome

A

ASDs + Lamotrigine

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17
Q

CONVENTIONAL ANTISEIZURE

Status Epilepticus
and Other
Convulsive
Emergencies

A

IV Diazepam (rapidly
absorbed) followed by
Phenytoin
Lorazepam
Phenobarbital; and
Phenytoin

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18
Q

RECENTLY DEVELOPED ANTISEIZURES

Lennox-Gastaut
Syndrome

A

Felbamate
Adjunct: Topiramate
Clobazam

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19
Q

RECENTLY DEVELOPED ANTISEIZURES

Status Epilepticus
and Other
Convulsive
Emergencies

A

IM Midazolam

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20
Q

considered equally effective for generalized absence

A

Ethosuximide & Valproate:

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21
Q

D.O.C. for generalized tonic-clonic and for
myoclonic seizures, particularly in the syndrome of
Juvenile Myoclonic Epilepsy

A

Valproate

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22
Q

also demonstrated to be efficacious AS
AN ADJUNCT (additional only) for refractory (not
responsive to initial treatment) Generalized Myoclonic

A

Levetiracetam

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23
Q

Enhancement of GABA neurotransmission through actions on

A

GABAA receptors

Modulation of GABA metabolism

Inhibition of GABA reuptake into the synaptic
terminal

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24
Q

actions on the synaptic vesicle protein SV2A or Ca 2+ channels containing the α2δ subunit

A

Modulation of synaptic release

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25
Q

This period is also thought to be the refractory period, where neuronal cell may be rendered
unresponsive to any form of stimulation for a short time

A

Depolarization

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26
Q

Molecular Target
& Activity

Enhance fast inactivation (shortens recovery period from
inactivation)

A

Phenytoin (PHT)
Carbamazepine
(CBZ)
Lamotrigine (LTG)
Felbamate (FBM)
Topiramate (TPM)
Oxcarbazepine
(OxCBZ)
Valproate (VPA)
Eslicarbazepine
(ESL)
Rufinamide (RUF)

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27
Q

Molecular Target
& ActivityMolecular Target & Activity

Enhance slow
inactivation (prolongs
inactivated state)

A

Lacosamide (LCM)

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28
Q

Consequence of Action

Lacosamide (LCM)

A

↑ Spike frequency adaptation (not really important_

↓ AP bursts, focal firing,
and seizure spread

Stabilize neuronal
membrane

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29
Q

Molecular Target &
Activity

GABAA receptor
allosteric modulators

A

Benzodiazepines
(BZDs)
Phenobarbital (PB)
Felbamate (FBM)
Primidone (PRM)
Carbamazepine
(PRM))
Oxcarbazepine
(PRM)
Topiramate (TPM)
Clobazam (CLB)
Stiripentol (STP)

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30
Q

Consequences of Action

Benzodiazepines
(BZDs)
Phenobarbital (PB)
Felbamate (FBM)
Primidone (PRM)
Carbamazepine
(PRM))
Oxcarbazepine
(PRM)
Topiramate (TPM)
Clobazam (CLB)
Stiripentol (STP)

A

↑ Membrane
hyperpolarization and seizure threshold (anything that increases GABA activity also increases membrane
hyperpolarization)

↓ Focal firing
(BZDs—attenuate
spike-wave discharges;
PB, CBZ, OxCBZ—aggravate spike-wave
discharges)

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31
Q

Molecular Target &
Activity

GABA uptake inhibitor/
GABA transaminase inhibitor

A

Tiagabine (TGB)
Vigabatrin (VGB)

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32
Q

Consequences of Action

Tiagabine (TGB)
Vigabatrin (VGB)

A

↑ Extrasynaptic GABA levels & membrane hyperpolarization

↓ Focal firing

Aggravate spike-wave
discharges

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33
Q

Inhibition of α2δ subunit on Ca 2+ channel → promote GABA release

A

Gabapentin
Pregabalin

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34
Q

Inhibition of SV2A → inhibits Glutamate release

A

Levetiracetam

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35
Q

Molecular Target & Activity

α2δ Ligands

A

Gabapentin (GBP)
Pregabalin (PGB)

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36
Q

Consequences of Action

Gabapentin (GBP)
Pregabalin (PGB)

A

Modulate neurotransmitter release discharges

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37
Q

Molecular Target
& Activity

SV2A protein ligand

A

Levetiracetam (LEV)
Brivaracetam (BRV)

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38
Q

Consequences of Action

Levetiracetam (LEV)
Brivaracetam (BRV)

A
  • Unknown; may decrease NTA release
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39
Q

predominantly expressed in neurons & are important determinants of cellular activity

A

KCNQ 2-5 channels

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40
Q

increases number of KCNQ channels that are open at rest and also prime the cell to respond with a larger, more rapid, and more prolonged response to membrane depolarization

A

Ezogabine (a.k.a. Retigabine)

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41
Q

KCNQ 2-5 channels

Seem to act like a brake to prevent the high levels of neuronal AP burst firing

A

epileptiform activity

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42
Q

levels increase with epileptic
condition

A

Carbonic Anhydrase

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43
Q

highly (>90%) bound to plasma proteins

can be displaced → temporary increased free fraction → transient toxicity but easily corrected

A

Phenytoin
Tiagabine
Valproate
Diazepam
Perampane

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44
Q

do not affect microsomal enzymes

A

Levetiracetam
Gabapentin
Pregabalin

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45
Q

Absorption

○ Almost complete (100%), slower with food (do not give it with food)

○ Peak levels: 6-8 hours

A

CARBAMAZEPINE

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46
Q

Distribution

○ slow, Vd = 1L/kg

○ 70% protein bound (no displacement observed)

A

CARBAMAZEPINE

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47
Q

Elimination

○ low systemic clearance = 1L/kg/day

○ microsomal enzyme inducer (biphasic elimination)

○ T ½ = 36 hours, 8-12
hours

A

CARBAMAZEPINE

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48
Q

Preparation

○ Oral form; extended release formulations

A

CARBAMAZEPINE

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49
Q

Dose

○ Higher dosage is achieved if given at multiple divided doses daily

○ If you give the extended release form, this may permit twice daily dosing

○ Pediatric: 15-25 mg/kg/day

○ Adults: maintenance dose is 800-1200 mg/d

○ maximum recommended dose is 1600 mg/d (Giving maximum dose is avoided because it
increases risk of adverse effects)

A

CARBAMAZEPINE

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50
Q

Therapeutic plasma level:

4-8 mcg/ml

A

CARBAMAZEPINE

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51
Q

○Focal seizure

○ Focal-to-bilateral tonic-clonic seizure

○ Trigeminal and glossopharyngeal neuralgia

○ Mania in Bipolar Disorder

○ There’s anecdotal evidence that it may be
effective in treatment of generalized tonic clonic
(idiopathic generalized epilepsies)

○ Use it with caution because it can exacerbate absence and myoclonic seizures

A

CARBAMAZEPINE

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52
Q

CARBAMAZEPINE

increase the rate of the metabolism (Inducer -
decrease the plasma concentration)

A

Primidone, Phenytoin, Ethosuximide,
Valproic acid, Clonazepam, Warfarin, Oral contraceptives, Doxycycline, Haloperidol

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53
Q

CARBAMAZEPINE

inhibit carbamazepine clearance (Inhibitor -
increase the plasma concentration)

A

Propoxyphene, Troleandomycin, Valproic
Acid, lithium

■ e.g. Valproic Acid (inhibitor) +
Carbamazepine = increase plasma
concentration of Carbamazepine

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54
Q

increase carbamazepine

A

Cimetidine, Erythromycin, Isoniazid

■ e.g. Cimetidine (potent microsomal enzyme
inhibitor) + Carbamazepine = incr

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55
Q

decrease carbamazepine steady-state

A

Phenytoin, Phenobarbital

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56
Q

common, dose-related (the higher the dose, the greater the toxic effects)

■ ataxia, diplopia (if drug is above 7mcg/mL)

A

CARBAMAZEPINE

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57
Q

mild GI upsets, unsteadiness, drowsiness

■ hyponatremia, water intoxication

A

CARBAMAZEPINE

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58
Q

idiosyncratic (particular individuals)

■ erythematous skin rash

■ aplastic anemia, agranulocytosis

■ hepatic dysfunction

A

CARBAMAZEPINE

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59
Q

Remedy for Carbamazepine a/e

A

initiate at a lower dose then slowly increase
until you reach the therapeutic dose

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60
Q

10-keto analog of Carbamazepine

same moa as Carbamazepine

A

OXCARBAZEPINE

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61
Q

half life of OXCARBAZEPINE

A

1-2 hours

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62
Q

antiseizure activity resides almost exclusively in the active 10-hydroxy metabolites, S (+), and R (-) licarbazepine (also referred to as monohydroxy derivatives or MHDs)

A

OXCARBAZEPINE

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63
Q

● less potent than Carbamazepine (clinical dose may need to be 50% higher from that of carbamazepine to
obtain equivalent seizure control)

A

OXCARBAZEPINE

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64
Q

prodrug of S(+) - licarbazepine

A

ESLICARBAZEPINE ACETATE

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65
Q

effective half-life of S(+)-licarbazepine (oral
administration): 20-24 hours (long)

A

ESLICARBAZEPINE ACETATE

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66
Q

dosage: 400-1600 mg/d; titration typically required
for higher doses

A

ESLICARBAZEPINE ACETATE

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67
Q

eliminated primarily by renal excretion (Adjust dose if patient has renal impairment)

A

ESLICARBAZEPINE ACETATE

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68
Q

MOA: binds selectively to the fast inactivated state of sodium channels but the binding is much slower

A

LACOSAMIDE

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69
Q

Dose: administered BID with 50mg doses and
increasing by 100-mg increments weekly:
○ effective at 200 mg/d
○ greater and roughly similar overall efficacy at 400 and 600 mg/d

A

LACOSAMIDE

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70
Q

Clinical use: focal-to-bilateral tonic-clonic
(secondarily generalized seizures)

A

LACOSAMIDE

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71
Q

Adverse effects:
○ dizziness, headache, nausea, diplopia

A

LACOSAMIDE

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72
Q

Contraindication: phenylketonuria (PKU) - Avoid in patients because aspartame is source of
phenylalanine which is harmful for patients with PKU

A

LACOSAMIDE

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73
Q

Pharmacokinetics
○ rapidly and completely absorbed, with no food
effect

○ bioavailability nearly 100%

○ plasma concentrations are proportional to oral
dosage up to 800 mg

○ peak concentrations = 1 to 4 hours after oral
dosing

○ elimination half-life = 13 hours

A

LACOSAMIDE

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74
Q

Absorption:
● oral: salt form almost complete
● IM: unpredictable, precipitation occurs (unlike fosphenytoin)

A

PHENYTOIN

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75
Q

Distribution:
● peak plasma concentration: 3 to 12 hours
● steady state reached 5-7 d (low levels), 4-6 w (high
levels)

A

PHENYTOIN

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76
Q

highly protein bound
○ with uremia or hypoalbuminemia - total plasma
level

○ hyperbilirubinemia (bilirubin is also protein
bound)

○ liver disease or nephrotic syndrome (proteins
are excreted)

A

PHENYTOIN

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77
Q

CSF is proportionate to free plasma concentration

● volume of distribution: 0.6-0.7 L/kg in adults
(low Vd because highly protein bound)

● accumulates in the brain, liver, muscle, fat

A

PHENYTOIN

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78
Q

Elimination
● metabolized by CYP2C9 and CYP2C19 to inactive
metabolites
● dose-dependent

● Low blood levels - first order kinetics

● blood levels rise within the therapeutic range, the maximum capacity of the liver to metabolize the drug
is approached (saturation kinetics)
○ give at high doses, high blood levels, tendency
for phenytoin to accumulate

● T ½ (low to mid therapeutic range) = 24 hrs (12-36
hrs)
○ as half life increases markedly or prolonged,
steady state is not achieved because plasma
levels continue to rise

A

PHENYTOIN

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79
Q

therapeutic plasma level = 10/20 mcg/ml

when oral therapy is started, it is common to begin
adults at 300 mg/d, regardless of body weight

in adults, dosage should be increased in increments
of no more than 25-30 mg/d

A

PHENYTOIN

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80
Q

in children, dosage of 5 mg/kg should be followed by
readjustment after steady-state plasma levels are
obtained

predominant form is the sodium salt in an
extended-release pill (OD or BID)

free acid available in immediate-release suspension
and chewable tablets

Fosphenytoin sodium available for IV or IM use and
usually replaces IV phenytoin sodium

A

PHENYTOIN

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81
Q

Phenytoin displaced from protein binding (increase free form → increase transiently the toxicity)

A

Phenylbutazone, Sulfonamides, Valproate,
Warfarin

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82
Q

Phenytoin microsomal enzyme inducer

A

reduce its steady state: Carbamazepine,
Chloramphenicol, Corticosteroids, Haloperidol,
Quinidine, Theophylline, Oral Contraceptives,
Warfarin

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83
Q

reduce plasma levels of Valproic Acid, Tiagabine,
Ethosuximide, Lamotrigine, Topiramate,
Oxcarbazepine and MHDs, Zonisamide,
Felbamate, many Benzodiazepines, Perampane

A

Phenytoin

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84
Q

inhibit Phenytoin metabolism

A

INH, Cimetidine, Disulfiram, Doxycycline,
Phenylbutazone, Sulfas, Warfarin,
Chloramphenicol, Valproate

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85
Q

Adverse effects- dose-related
● Short-term
○ diplopia, ataxia, nystagmus, sedation, gingival
hyperplasia, hirsutism

A

PHENYTOIN

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86
Q

Adverse effects- dose-related

Long-term
○ coarsening of facial features, mild peripheral
neuropathy, osteomalacia (problem in Vit D
metabolism), megaloblastic anemia (folate
levels may be decreased)

A

PHENYTOIN

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87
Q

Adverse effects- dose-related

Others - Idiosyncratic reactions
○ lymphadenopathy, agranulocytosis, relatively
rare hypersensitivity (rash), fever, exfoliative
skin lesion

A

PHENYTOIN

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88
Q

MOA: inhibitor of GABA uptake (GAT-1 GABA
transporter

A

TIAGABINE

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89
Q

Structure: active moiety - nipecotic acid and a
lipophilic anchor (can pass through BBB)

A

TIAGABINE

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90
Q

Pharmacokinetics
○ bioavailability - 90 to 100%
○ linear kinetics
○ highly protein-bound
○ metabolism - hepatic oxidation by CYP3A
○ T ½ = 5 to 8 hrs
○ elimination: feces (60-65%), urine (25%)

A

TIAGABINE

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91
Q

○ second line treatment for focal seizures

A

TIAGABINE

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92
Q

initial dose - 4 mg/d with
○ weekly increments = 4-8 mg/d - to total doses =
16-56 mg/d (4 divided doses)

A

TIAGABINE

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93
Q

Adverse effects (dose-related)
○ Nervousness, dizziness, tremor, difficulty in
concentrating, depression
○ Requires discontinuation: excessive confusion,
somnolence, ataxia
○ rare: psychosis
○ uncommon: rash (idiosyncratic)

A

TIAGABINE

94
Q

Precaution: hepatic impairment
● Contraindication: generalized onset epilepsies

A

TIAGABINE

95
Q

MOA: an allosteric opener of KCNQ2-5
(Kv7.2-Kv7.5) voltage-gated potassium channels in
axons and nerve terminals → inhibits release of
various neurotransmitters (e.g. glutamate)

A

RETIGABINE (EZOGABINE)

96
Q

Clinical Use: focal seizures (3rd line)

A

RETIGABINE (EZOGABINE)

97
Q

Pharmacokinetics
○ Absorption
■ linear kinetics
■ not affected by food
○ major metabolic pathways: N-glucuronidation
and N-acetylation

A

RETIGABINE (EZOGABINE)

98
Q

Adverse effects - does not inhibit or induce CYP450
enzymes

○ dose-related: dizziness, somnolence, blurred vision, confusion, and dysarthria

○ urinary symptoms: retention, hesitation, and dysuria (KCNQ channels found in detrusor muscles promoting detrusor smooth muscle elaxation)

○ blue pigmentation (skin, lips, palate, sclera, and conjunctiva

○ ophthalmologic (3rd line because of this)

■ retinal pigment abnormalities

■ macular abnormalities (vitelliform lesions) -
macular degeneration type

■ decreased visual acuity

A

RETIGABINE (EZOGABINE)

99
Q

MOA: Na-channel blockade

A

LAMOTRIGINE

100
Q

Pharmacokinetics
○ No active metabolite
○ Nearly complete absorption (90%)
○ Vd = 1-1.4L/kg
○ Protein binding = 55%
○ Metabolism
■ Linear kinetics
■ Glucuronidation
■ t1/2 = 24hrs; 13-14hrs (w/ enzyme
inducers)

A

LAMOTRIGINE

101
Q

Dose = 100-300mg/d
○ Initial dose = 25 mg/d → increasing to 50 mg/d after 2 wks → titration by 50 mg every 1-2 wks → usual maintenance dose of 225-375 mg/d (in
2 divided doses)

A

LAMOTRIGINE

102
Q

Enzyme inducers?
- plasma conc of lamotrigine is
decreased (metab is enhanced)

A

Carbamazepine,
Oxcarbazepine, Phenytoin, Phenobarbital,
Primidone

103
Q

(inhibitor of Lamotrigine metabolism) → 2 fold inc. t1/2 (prolonged) → plasma conc of
lamotrigine is increased

Start at a lower dose: Reduce dose to
12.5-25 mg every other day, with increases
of 25-50 mg/d every 2 weeks as needed to a
usual maintenance dose of 100-200 mg/d
(lower)

A

Valproate

104
Q

Adverse Effects
○ Dizziness, headache, diplopia
○ Nausea
○ Insomnia
○ Somnolence
○ Skin rash, hypersensitivity
■ Can be life-threatening bc it might progress
to hypersensitivity among pedia pt (1-2%)
■ Serious rash can occur in 0.3-0.8% of
children bet 2-17 y/o
■ In adults: 0.08-0.3%

A

LAMOTRIGINE

105
Q

MOA: Binds selectively to a synaptic vesicular
protein SV2A → reduces the release of excitatory
NTA glutamate

SV2A: an integral part of vesicle membrane protein w/c
promotesthe release of NTAs via exocytosis

A

LEVETIRACETAM

106
Q

Dose = 500-1000 mg/d BID
○ Increased every 2-4 wks by 1000 mg to a max
dose of 3000 mg/d
○ From Doc: Usually 2000 mg/d

A

LEVETIRACETAM

107
Q

Pharmacokinetics

○ Absorption
■ Nearly complete, rapid, unaffected by food

Peak plasma concentration = 1.3 hrs

Distribution: <10% protein binding

Elimination
■ Linear
■ t1/2 = 6-8 hrs
■ 2/3 excreted unchanged in urine
■ Metabolized in the bld

A

LEVETIRACETAM

108
Q

Available Preparations
○ Oral formulations extended-release tablets
○ IV prep

A

LEVETIRACETAM

109
Q

Drug Interactions: Minimal
○ Neither does it inhibit or induce microsomal
enzymes

A

LEVETIRACETAM

110
Q

Adverse effects:
○ Somnolence
○ Asthenia
○ Ataxia
○ Infection (colds)
○ Dizziness
○ Idiosyncratic reactions
○ Less common more serious: Behavioral and
mood changes - irritability, aggression, agitation,
anger, anxiety, apathy, depression, and
emotional lability

A

LEVETIRACETAM

111
Q

4-n-propyl analog of Leviracetam w/ high-affinity to SVA2A ligand

A

BRIVARACETAM

112
Q

Approved clinical use: Focal (partial) onset seizures

A

BRIVARACETAM

113
Q

Pharmacokinetics
○ Rapidly and completely absorbed after oral
administration
○ Low plasma protein-binding (<20%)
○ Linear over a wide dose range (10-600 mg, single
oral dose); twice daily dosing
○ Elimination half-life = 7-8hrs

A

BRIVARACETAM

114
Q

Drug Interactions
○ With Carbamazepine → carbamazepine epoxide
(active metab of carba) → INC a/e of carba
○ With Phenytoin → INC phenytoin lvl

A

BRIVARACETAM

115
Q

MOA: Potent non-competitive antagonist of the AMPA receptor

Binds to an allosteric site of the extracellular
side of the channel, acting as a wedge to prevent
channel opening

■ AMPA receptor → critical to generation of
local seizure activity in an epileptic foci

■ Responsible for synchronization of
impulses

● From Doc: If you give Perampanel w/ CYP3A4 inducing agents,
you may have to give it at a higher dose

A

PERAMPANEL

116
Q

Clinical Use
○ Focal and focal-to-bilateral tonic-clonic seizures

○ Generalized tonic-clonic seizures

○ Maintenance dose (12 y/o and older) = 4, 6, or 8 mg/d

A

PERAMPANEL

117
Q

Adverse Effects (dose-dependent)

○ Dizziness, somnolence, and headache

○ Behavioral (aggression, hostility, irritability. and
anger)

■ From Doc: Pag AMPA – pagka Glutamate receptor inhibition, usually s/e is behavioral

■ Common din in YOUNG ppl and those w/ learning
disabilities or dementia

A

PERAMPANEL

118
Q

Pharmacokinetics
○ From Doc: Food SLOWS down its absorption

○ Absorption is rapid and drug is fully bioavailable

○ Half-life = 70-110 hrs (prolonged in moderate
hepatic failure)

○ Steady state is not achieved for 2-3 wks

○ Kinetics are linear in the dose range of 2-12
mg/d

○ 95% bound to plasma proteins

○ Metabolism: Oxidation by CYP3A4 and glucuronidation

A

PERAMPANEL

119
Q

Drug Interactions
○ From Doc: Behavioral effects are more common in younger
pt

○ CYP3A4-inducing anti-seizures
(Carbamazepine, Oxcarbazepine, and
Phenytoin) - INC clearance by 50-70%

○ Alcohol - exacerbate anger level

○ Levonorgestrel-containing hormonal
contraceptives - decreased effectiveness

A

PERAMPANEL

120
Q

MOA: Enhancement of inhibition at
neurotransmission synapses mediated by
GABA-acting at GABA receptors by increasing mean open duration of Cl- channel w/o altering
conductance or opening frequency

○ Depress voltage → activated calcium currents

○ Blockage of AMPA receptors

○ From Doc:
■ They are positive allosteric modulators at a LOW concentration. If the phenobarbsis at a HIGH concentration → directly activation of GABA-A receptor

■ Di na sya 1st choice cosit has a lot of a/e (kaya dun ka sa first choice ka beh)

■ This drug must be discontinued overseveral wksto
avoid recurrence ofsevere seizures/status
epilepticus(i-tapersis)

A

. PHENOBARBITAL

121
Q

Clinical Uses
○ Focal seizures

○ Generalized tonic-clonic seizures

○ Juvenile myoclonic epilepsy

● From Doc: DO NOT USE IN ABSENCE OR INFANTILE SPASMS
→ WORSENS

A

. PHENOBARBITAL

122
Q

Dose = 6-200 mg, BID or TID

○ Minimally effective dose = 60 mg/d

○ Median effective dose = 100-150 mg/d

○ Accepted serum concentration = 15-40 mcg/mL (may tolerate chronic lvl if >40 mcg/mL)

A

. PHENOBARBITAL

123
Q

Pharmacokinetics
○ Absorption: Rapid and complete
○ Distribution: Onset of action 10-60 mins
■ Crosses placenta
■ Undergo redistribution

A

. BARBITURATES

124
Q

Biotransformation
■ Major pathway: Oxidation at C5 → alcohol, ketones, phenols, & carboxylic acid

■ N-glycosylation (Phenobarbital)

■ N-deakylation (Mephobarbitalto
Phenobarbital)

■ From Doc: Its metabolic elimination is more rapid in younger people, BUT slower in elderly and infants

■ If your pt is PREGNANT and is given this drug, its t1/2 tendsto PROLONG d/t expanded V.D. for
preggo

■ Chronic liver dse → prolonged t1/2

■ Repeated administration → shortenst1/2 bec
phenobarb will induce ITS OWN metabolism
(common for long-acting agents)

A

BARBITURATES

125
Q

Excretion: Urine

A

BARBITURATES

126
Q

Adverse Effects
○ After-effects
■ Residual CNS depression
■ Subtle distortion of mood (irritability,
temper)
■ Impairment of judgment and fine motor
skills
■ Other residual effects: Vertigo, vomiting,
nausea, or diarrhea
■ Awaken slightly intoxicated, euphoric, and
energetic

A

BARBITURATES

127
Q

Adverse Effects

Paradoxical Excitement (geriatric/debilitated
individuals) – common in Phenobarbital and Methylphenobarbital (methylbarbital sabi ni doc tho)

Restless, excited, delirium, worsens pain
perception

Hypersensitivity

Respiratory depression

Tolerance and dependence

A

BARBITURATES

128
Q

Drug Interactions
○ Enhances CNS depression

■ Ethanol, antihistamines, isoniazid,
methylphenidate, monoamine oxidase

○ Absorption of calcium is inhibited

○ CCl4 (carbon tetrachloride) → HIGH risk of hepatotoxicity

○ Competitively enhances metabolism of the ff since barbs is an enzyme INDUCER:

■ Steroid hormones, cholesterol, bile salts, vit K and D, dicumarol, phenytoin, digitalis
compound, griseofulvin,
oral contraceptives

■ Effect? Low plasma conc of these drugs

A

BARBITURATES

129
Q

MOA: Acts more like the sodium-channel blocking anti-seizure drugs than phenobarbital

A

PRIMIDONE (2-DEOXY PHENOBARBITAL)

130
Q

Clinical Use
○ Focal seizures (complex partial seizure daw to w/ impaired awareness)

○ Generalized tonic-clonic seizures

● From Doc: Carbamazepine and Phenytoin are more superior to
Primidone

A

PRIMIDONE (2-DEOXY PHENOBARBITAL)

131
Q

Pharmacokinetics
○ Peak concentration = 3hrs (oral)

○ VD = 0.6L/kg

○ 70% unbound

○ Metabolized by oxidation → conjugation

■ Metabolites: Phenobarbital and PEMA (active metabolite)

■ PEMA: Minimal contribution to its efficacy

○ t1/2 = 6-8hrs; PEMA = 8-12hrs

○ Clearance = 2K/kg/day

○ From Doc: Slowly metabolized sa newborns and elderly

A

PRIMIDONE (2-DEOXY PHENOBARBITAL)

132
Q

Therapeutic Levels
○ Parent drug steady-state = 30-40 hrs
○ Active metabolites
■ Phenobarbital = 20 days
■ PEMA = 3-4 days
○ Plasma Level
■ Primidone: 8-12 mcg/ml
■ Phenobarbital: 15-30 mcg/ml
○ To increase the dose, it is done days to weeks

A

PRIMIDONE (2-DEOXY PHENOBARBITAL)

133
Q

MOA
○ use-dependent block of N-methyl-d–aspartate (NMDA) receptors, with selectivity for those
containing the GluN2B (NR2B) subunit

○ Barbiturate-like potentiation of GABA-A
receptor responses (allosteric modulator)

A

FELBAMATE

134
Q

Clinical Use:
○ Refractory seizures
■ For cases that are not responsive to conventional tx

○ Focal seizures

○ Lennox-Gastaut syndrome

A

FELBAMATE

135
Q

Pharmacokinetics
○ Preparation: oral form (well absorbed, >90%)

○ Metabolism: hydroxylation, conjugation
(CYP3A4 and CYP2E1)

○ T1/2 = 20 hrs;

■ 13-14 hrs when taken with phenytoin or
carbamazepine (inducers)

○ Excretion: 30-50% is excreted unchanged in the urine

A

FELBAMATE

136
Q

● Drug dosage: 400 mg TID (max 3600 mg/d)

A

FELBAMATE

137
Q

Therapeutic plasma level: 30-100 mcg/ml

A

FELBAMATE

138
Q

Adverse effects
○ Aplastic anemia
○ Severe hepatitis
○ Only a third line drug because of AE

A

FELBAMATE

139
Q

Drug interactions
○ Shorten T1/2
: phenytoin, carbamazepine
○ Plasma levels increased: phenytoin
○ Plasma levels decreased: carbamazepine

A

FELBAMATE

140
Q

MOA:
○ Blockade of NMDA receptor-mediated
excitation
○ Facilitate glutamic acid decarboxylase (GAD)
○ Inhibit GABA transporter GAT-1
○ Inhibit GABA transaminase (GABA-T)

A

VALPROATE & DIVALPROEX SODIUM

141
Q

Pharmacokinetics:
○ Bioavailability: 80%
○ Peak plasma blood levels achieved in 2 hrs
○ 90% plasma protein-bound
○ Highly ionized
○ Vd = 0.15 L/kg
○ T1/2 = 9-18 hrs

A

VALPROATE & DIVALPROEX SODIUM

142
Q

Therapeutic levels and dosage
○ Dose: 25-30 mg/kg/d (max 60 mg/kg/d)
○ Therapeutic levels= 50-100 mcg/ml

A

VALPROATE & DIVALPROEX SODIUM

143
Q

Clinical use
○ DOC for
■ Absence with generalized tonic-clonic
seizures
■ Myoclonic seizures (juvenile myoclonic
epilepsy)
○ Partial seizures
○ Atonic attacks (Lennox-Gastaut syndrome)
○ Bipolar disorders
○ Migraine prophylaxis (not first line)

A

VALPROATE & DIVALPROEX SODIUM

144
Q

an enzyme inhibitor

○ Decrease levels from increase metabolism with carbamazepine (enzyme inducer)

○ Increase levels with antacid (increase
absorption)

○ Displaces phenytoin from protein-binding →
phenytoin free-form will increase

○ Displaced from protein-binding sites by
salicylates

Inhibits metabolism of phenobarbital,
ethosuximide, lamotrigine

○ When used with clonazepam may precipitate
absence status

A

VALPROATE & DIVALPROEX SODIUM

145
Q

Adverse effects
○ Most common, dose-related
■ GI complaints: nausea, vomiting, abdominal
pain, heartburn
■ Start with lower dose to avoid

○ Fine tremor (high doses)

○ Uncommon reversible adverse effects
■ Weight gain, increased appetite, hair loss

○ Idiosyncratic:
■ Hepatotoxicity
■ Thrombocytopenia

○ Teratogenic:
■ Spina bifida
■ Other congenital abnormalities:
Cardiovascular, orofacial, digital
■ If given in the 1st 14 weeks
■ Decreases folic acid

A

VALPROATE & DIVALPROEX SODIUM

146
Q

MOA:
○ Blocks voltage-gated Na
+ channels
○ Potentiates effects of GABA
○ Depresses excitatory action of kainate or AMPA
receptors
○ Weak inhibitor of carbonic anhydrase
isoenzymes 2 and 4
■ This doesn’t account for antiseizure activity
■ But may cause metabolic acidosis

A

TOPIRAMATE

147
Q

Pharmacokinetics
○ Rapidly absorbed
○ Food doesn’t affect absorption
○ Bioavailability: 80%
○ Protein-binding: 15%
○ Metabolism: 20-50%
○ T1/2
: 20-30 hrs
■ If given with enzyme inducers, T1/2 will
shorten to 12-15 hrs
○ Primary route of excretion: renal

A

TOPIRAMATE

148
Q

● Dose
○ Initial dose= 100 mg/d
○ 200-600 mg/d

A

TOPIRAMATE

149
Q

Clinical Use
○ Focal seizures
○ Primary generalized tonic-clonic seizures
○ Lennox-Gastaut syndrome
○ Juvenile myoclonic epilepsy, infantile spasms
○ Dravet’s syndrome (severe myoclonic epilepsy in
infancy)
○ Childhood absence seizures
○ Migraine headaches

A

TOPIRAMATE

150
Q

Drug interactions
○ OCPs (oral contraceptives): reduced
contraceptive effect

A

TOPIRAMATE

151
Q

Adverse effects
○ Dose-related, 1st 4 weeks

○ Somnolence, fatigue, dizziness, cognitive
slowing, paresthesias, nervousness, confusion

○ Requires discontinuation if px experience:
■ Acute myopia
■ Glaucoma

○ Urolithiasis

○ Fatigue, anorexia, or nausea and vomiting
■ Carbonic anhydrase inhibition → dec serum
HCO3 → metabolic acidosis

○ Long-term therapy: weight loss peaks at 12-18 months after initiation of therapy

○ Teratogenic in animals → hypospadias
■ Oral cleft in newborns

A

TOPIRAMATE

152
Q

Sulfonamide derivative

A

ZONISAMIDE

153
Q

Pharmacokinetics:
○ Good bioavailability

○ Low protein-binding (>50-60%)

○ Linear kinetics

○ T1/2 = 1-3 days

○ Metabolism:
■ Acetylation (N-acetyl-zonisamide)
■ CYP3A4
(2 sulfamoylacetylphenol)

○ Renal excretion

A

ZONISAMIDE

154
Q

Dose
○ Maintenance doses are 200-400 mg/d in adults (max 600 mg/d)

○ 4-8 mg/kg/d in children (max 12 mg/kg/d)

A

ZONISAMIDE

155
Q

Adverse effects
○ Drowsiness
○ Cognitive impairment
○ Skin rash
○ Renal stone

A

ZONISAMIDE

156
Q

Drug interactions
○ Carbamazepine, phenytoin and phenobarbital -
increase clearance

A

ZONISAMIDE

157
Q

MOA: block voltage-gated Na
+ channels

A

ZONISAMIDE

158
Q

Clinical use: Myoclonic epilepsies and in infantile
spasms

A

ZONISAMIDE

159
Q

Drug of choice for generalized absence seizure

A

ETHOSUXIMIDE

160
Q

Main action: inhibition of low-voltage-activated
T-type calcium channels in thalamocortical
neurons

■ Thalamocortical neurons: where impulses
fire for absence seizures

■ T-type calcium channels provide pacemaker
current in these neurons and would
generate rhythmic cortical discharge of an
absence attack

■ If calcium channels are inhibition, it will
reduce synchronization and propagation of
impulses

○ Other actions:

■ Inhibit voltage-gated sodium channels

■ Inhibit inward rectifier potassium channels

A

ETHOSUXIMIDE

161
Q

Pharmacokinetics
○ Oral absorption: complete
○ Peak concentration: 3-7 hrs
○ Not protein-bound
○ Metabolism: hydroxylation (CYP3A4)
○ Clearance: 0.25 L/kg/d
○ T1/2 = 40 hrs (18-72 hgrs)

A

ETHOSUXIMIDE

162
Q

Therapeutic levels and Dosage
○ Therapeutic range: 60-100 mcg/ml
○ Dose: 750-1500 mg/d (single or 2-3 divided
doses)
■ Single dose because of long T1/2
, but can be
divided to minimize GI AE
○ Children:
■ Initial dose: 10-15 mg/kg/d
■ Maintenance dose: 15-40 mg/kg/d
○ Older children and adults:
■ Initial dose: 250-500 mg/d
■ Increasing in 250-mg increments, maximum
of 1500 mg/d
○ Therapeutic serum concentration: 40-100
mcg/mL
○ Linear relationship between dose and
steady-state concentration
○ Narrow spectrum

A

ETHOSUXIMIDE

163
Q

Drug interactions
○ Valproic acid (inhibitor) - decrease its clearance, increase plasma concentration

A

ETHOSUXIMIDE

164
Q

Adverse Effects
○ Dose-related: Gastric distress, transient
lethargy or fatigue, headache, dizziness, hiccup, euphoria

○ Non-dose related/Idiosyncratic: Skin rash, Stevcens-Johnson syndrome, SLE

A

ETHOSUXIMIDE

165
Q

Oxazolidinedione

A

TRIMETHADIONE

166
Q

Clinical use: Generalized absence seizures (old DOC)

A

TRIMETHADIONE

167
Q

Major metabolites: paramethadione & dimethadione

A

TRIMETHADIONE

168
Q

Adverse effects:
○ Dose-related and idiosyncratic: Hemeralopia
(day blindness)

A

TRIMETHADIONE

169
Q

DRUGS EFFECTIVE FOR MYOCLONIC SEIZURES
(SYNDROME OF JUVENILE MYOCLONIC EPILEPSY)

A

DOC: Valproate

170
Q

DRUGS EFFECTIVE FOR MYOCLONIC SEIZURES
(SYNDROME OF JUVENILE MYOCLONIC EPILEPSY)

A

Alternatives: Levetiracetam, Zonisamide,
Topiramate, Lamotrigine

171
Q

DRUGS EFFECTIVE FOR ATONIC SEIZURES SUCH
AS IN THE LENNOX-GASTAUT SYNDROME

A

Valproate in combination with lamotrigine and a
BZD
● Topiramate
● Felbamate
● Lamotrigine
● Use with caution: Phenobarbital and Vigabatrin

172
Q

1, 5-benzodiazepine

A

CLOBAZAM

173
Q

MOA: positive allosteric modulator of GABA-A
receptors

A

CLOBAZAM

174
Q

Clinical use: only for Lennox-Gastaut syndrome (2
years of age or older)

A

CLOBAZAM

175
Q

Pharmacokinetics
○ T1/2
: 18 hours
○ Metabolism: CYP and non-CYP transformations
(14 metabolites)
○ Major metabolite: Desmethylclobazam
(norclobazam)
■ T1/2
: 8-20 times higher

A

CLOBAZAM

176
Q

Adverse effects: dose-dependent
○ Somnolence and sedation, dysarthria, drooling,
behavioral changes (aggression)
○ Withdrawal symptoms with abrupt
discontinuation

A

CLOBAZAM

177
Q

Drug interaction
○ Moderate inhibitor of CYP2D6 → increase
plasma levels of phenytoin and carbamazepine

A

CLOBAZAM

178
Q

MOA: blocker of voltage-gated Na
+ channels

A

RUFINAMIDE

179
Q

Clinical Use:
○ Children
■ 10 mg/kg/d in two equally divided doses
(initial dose) and gradually increased to 45
mg/kg/g
■ Maximum dose: 3200 mg/d
○ Adults
■ 400-800 mg/d in two equally divided doses
(initial dose)
■ Maximum dose: 3200 mg/d
○ Given with food

A

RUFINAMIDE

180
Q

Pharmacokinetics
○ Well-absorbed
○ Peak plasma concentrations: 4-6 hrs
○ T1/2
: 6-10 hrs
○ Minimal plasma protein binding
○ Extensive non-cytochrome metabolism
○ Excreted in the urine

A

RUFINAMIDE

181
Q

Drug interactions: clearance decreased by valproate

A

RUFINAMIDE

182
Q

Adverse effects: somnolence, vomiting

A

RUFINAMIDE

183
Q

Still a new drug

A

RUFINAMIDE

184
Q

Severe myoclonic epilepsy of infancy

○ Rare genetic epileptic encephalopathy

○ Characterized by diverse generalized and focal seizure types

Child may present with myoclonic, tonic-clonic,
absence, atonic, and one-sided hemiconvulsive
and focal seizures

○ Due to mutations in SCN1A gene encoding
NAV.1 voltage-gated dependent Na
+ channels
and cause 79% of Dravet’s Syndrome

○ If there is a mutation in the SCN1A gene, Na
+ channel blocking antiseizure drugs are
contraindicated because this worsens seizures

A

Dravet’s Syndrome

185
Q

Aromatic allylic alcohol

A

STIRIPENTOL

186
Q

Used in conjunction with clobazam or valproate

A

STIRIPENTOL

187
Q

Pharmacokinetics: Nonlinear
○ Clearance decreases as dose increases

A

STIRIPENTOL

188
Q

Dosage: started at 10 mg/kg/d and is increased
gradually as tolerated

A

STIRIPENTOL

189
Q

Drug interaction
○ Potentinhibitor of CYP3A4, CYP1A2,
CYP2C19
○ Increases levels of clobazam and norclobazam

A

STIRIPENTOL

190
Q

Adverse effects
○ Sedation/drowsiness, reduced appetite, slowing
of mental function, ataxia, diplopia, nausea,
abdominal pain

A

STIRIPENTOL

191
Q

DRUGS EFFECTIVE FOR INFANTILE SPASMS
(WEST’S SYNDROME)

A

ACTH IM injection or Oral Corticosteroids
(prednisone or hydrocortisone)
○ associated with substantial morbidity
● Vigabatrin - can cause loss of vision
● Valproate
● Topiramate
● Zonisamide
● BZD (Clonazepam or Nitrazepam)

192
Q

S(+) enantiomer is active and the R(-) enantiomer
appears to be inactive

A

VIGABATRIN

193
Q

Pharmacodynamic activity of this drug is more
prolonged and not well-correlated with its half-life
because recovery from the drug requires synthesis
and replacement of GABA-T (because inhibition is
irreversible

A

VIGABATRIN

194
Q

MOA
○ Irreversibly inhibits GABA Transaminase
(GABA-T) → inhibits metabolism of GABA
○ Inhibition of synaptic GABA-A receptor
responses
○ Prolongs the activation of extrasynaptic
GABA-A receptors
○ Produces a sustained increase in the
extracellular concentration of GABA in the brain

A

VIGABATRIN

195
Q

Duration of action not correlated with half-life

A

VIGABATRIN

196
Q

Clinical Use
○ Focal seizures (but not generalized seizures)
○ Treatment of infantile spasms associated with
tuberous sclerosis

A

VIGABATRIN

197
Q

Dose
○ Infants: 50-150 mg/kg/d

Adults: initial oral dosage of 500 mg BID, total of
2-3 g/d

A

VIGABATRIN

198
Q

Pharmacokinetics
○ Complete absorption
○ Peak plasma concentration: 1hr
○ Nor protein bound
○ T1/2
: 6-8 hrs
○ Not metabolized
○ Excretion: urine (unchanged)

A

VIGABATRIN

199
Q

Adverse Effects
○ Irreversible retinal dysfunction
○ Permanent bilateral concentric visual field
constriction
■ Often asymptomatic but can be disabling
■ Onset of vision loss can occur within weeks
of starting the treatment or after months or
years
○ Somnolence, Headache, Dizziness, Weight gain
○ Less common: agitation, confusion and psychosis

A

VIGABATRIN

200
Q

Relative Contraindication: Mental illness (Psychotic
disorders)

A

VIGABATRIN

201
Q

MECHANISM OF ACTION

Bind to specific GABAA
receptor subunits at central nervous
system (CNS) neuronal synapses facilitating GABAmediated chloride ion channel opening FREQUENCY

● Positive allosteric modulators but do not activate the
GABA receptor directly

● Difference from Barbiturates

○ PROLONG the open state of the chloride
channels

○ Low concentration: positive allosteric
modulator
○ high concentration: can directly activate the
GABA receptor

Enhance membrane hyperpolarization

A

BENZODIAZEPINES

202
Q

ACTIONS: CNS (Review. Doc skipped slides cos same lang

● Sedation

● Hypnosis
○ Decreased anxiety

○ Muscle relaxation

■ Inhibit polysynaptic reflexes and
internuncial transmission

■ Inhibit transmission at skeletal neuromuscular junction

○ Anterograde amnesia

○ Anticonvulsant activity (Clonazepam,
Nitrazepam, Lorazepam, Diazepam)

○ Anesthesia (Diazepam, Midazolam)

A

BENZODIAZEPINES

203
Q

Ethanol - increase rate of absorption

● Cimetidine } inhibit N-dealkylation &
3-hydroxylation

● Oral contraceptives } - inhibits metabolism

● Erythromycin, Clarithromycin, Ritonavir,
Itraconazole, Ketoconazole, Grapefruitjuice (inhibit
CYP3A4)
○ Inhibit BZ metabolism

● Ethanol, Opioid analgesics, Anticonvulsants,
Phenothiazines, Antihistamines, TCA
○ Additive effect on CNS depression

A

BENZODIAZEPINES

204
Q

Seizure disorder
○ Status epilepticus

FIRST LINE TREATMENT

A

DIAZEPAM

205
Q

Seizure disorder
○ Status epilepticus

ALTERNATIVE

A

LORAZEPAM

206
Q

Seizure disorder
○ Status epilepticus

PREERRED IN THE OUT-OF-HOSPITAL (IM IF YOU CAN’T GIVE IV LINE)

A

MIDAZOLAM

207
Q
  • absence, atonic, and myoclonic
    seizure
A

CLONAZEPAM

208
Q
  • infantile spasms and myoclonic
    seizures
A

NITRAZEPAM

209
Q

BENZODIAZEPENE FOR FOCAL SEIZURE

A

Clorazepate dipotassium

210
Q

BENZODIAZEPENE FOR ATONIC SEIZURE

A

CLOBAZAM

211
Q

MECHANISM OF ACTION

Note: Bicarbonate efflux thru GABA receptors that can exert a
depolarizing/excitatory influence especially relevant during
intense GABA receptor activation which occurs during seizure. This happens when there is diminution of the
hyperpolarizing chloride gradient. As entry of chloride decreases (after GABA activation), bicarbonate enters.

● Inhibitors of carbonic anhydrase, particularly the cytosolic forms CA II and CA VII —> prevents
replenishment of intracellular bicarbonate —>
depresses depolarizing action of bicarbonate

○ So even if the chloride efflux is decreasing already in amount, you don’t expect intense receptor activation due to bicarbonate because it islost after inhibiting carbonic anhydrase

A

`CARBONIC ANHYDRASE INHIBITORS

212
Q

Prototype: Sulfonamide acetazolamide

A

CARBONIC ANHYDRASE INHIBITORS

213
Q

CLINICAL USE:
● Focal and generalized tonic-clonic seizures and especially generalized absence seizures

● Intermittent treatment of menstrual seizure
exacerbations

A

CARBONIC ANHYDRASE INHIBITORS

214
Q

ADVERSE EFFECT:
● Tolerance

A

CARBONIC ANHYDRASE INHIBITORS

215
Q

DOSE: 10 mg/kg/day to a maximum of 1,000 mg/day
***Topiramate and Zonisamide - sulfonamide derivatives - they have weak carbonic anhydrase activity

A

CARBONIC ANHYDRASE INHIBITORS

216
Q

When to initiate treatment in patients who had a
seizure (conditions where risk of recurrence may be high)

A

Pre-existing neurological disorder or
developmental delay

○ With family history of seizure

○ With abnormal neurologic exam

○ An abnormal EEG

○ Abnormal MRI that carries risk for recurrence
■ Tumor in cortico-thalamic area

○ Complicated febrile seizure and epilepsy for
children (i.e., the febrile seizure lasted >15 mins,
was one sided, or was followed by a second
seizure in the same day)
■ Diazepam for children at the time of fever
● Rectally - to avoid side effects of the drug when given chronically

217
Q

Goal of initiating treatment:

A

To reduce recurrence

218
Q

Choice for drug treatment (antiseizure)

Still the best - lesser adverse effects
(overlapping adverse effects - ataxia, GI
adverse effects)

A

Monotheraphy

219
Q

Dose initiated at reduced amount and adjusted at
appropriate intervals

A

Titration takes 1-2 weeks

220
Q

Duration of therapy

A

At least 2 years seizure-free
○ Tapering and discontinuation - to avoid rebound
seizures or status epilepticus

221
Q

Degree of success varies as a function of:

A

Seizure type
○ Cause - may be due to electrolyte imbalance
(correct it first)
○ Other factors

222
Q

Measurement of drug concentrations in plasma
facilitates optimizing antiseizure medication,
especially when:

A

Therapy is initiated
○ After dosage adjustments
○ In the event of therapeutic failure
○ When toxic effects appear
○ Multiple-drug therapy is instituted - especially
Valproate (can inhibit metabolism)
■ Give lower dose with the 2nd agent - to
monitor if the 2nd agent isreally reaching the
therapeutic plasma level

223
Q

(very teratogenic esp during 1st trimester -spina bifida)

A

Valproate

224
Q

Cleft lip and cleft palate

A

Topiramate

225
Q

Major congenital cardiac defect

A

Phenobarbital

226
Q

Low risk antiseizure drugs for pregnant women

A

carbamazepine, phenytoin, and levetiracetam

227
Q

What are the Effects on Vitamin K metabolism in pregnant women

A

ASDs that induce CYPs have been associated
with Vitamin K deficiency in the newborn —>
coagulopathy and intracerebral hemorrhage

228
Q

Treatment for vit k. deficiency due to antiseizure drugs

A

Treatment: Vitamin K1, 10 mg/day during the
last month of gestation for prophylaxis

229
Q

drugs that can penetrate into
breast milk in relatively high concentration

A

Primidone, Levetiracetam, Gabapentin,
Lamotrigine, and Topiramate:

230
Q

drugs that do not penetrate into breastmilk

A

Valproate, Phenobarbital, Phenytoin, and
Carbamazepine

231
Q

suicidality

A

Lamotrigine, Levetiracetam, and Topiramate

232
Q

Typically, ___% of recurrence will occur within __ months of
discontinuing the therapy for these types of seizures

A

80% and 4 months

Med (6 decks)

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