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PHRM 845 Module #1 > Lectures 48-49 - Pharmacotherapy of Seizure Disorders > Flashcards

Lectures 48-49 - Pharmacotherapy of Seizure Disorders Flashcards

1
Q

Lowering the seizure threshold: medications

A

usual doses: bupropion, clozapine, theophylline, varenicline, phenothiazine, antipsychotics, CNS stimulants (amphetamines)
high doses and impaired renal function: carbapenems, lithium, meperidine, penicillin, quinolones, tramadol

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2
Q

Quality of life monitoring

A

seizure frequency
functional status – evaluation of ability to continue employment, school, elderly living status; and role activities in everyday life
social functioning - driver’s license?
mental health status - depression is a common co-morbidity
Cognition – many antiseizure medications can have cognitive side effects
Number of doses of drug per day – streamline drug regimen cost of drug therapy - can the patient afford it?

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3
Q

Lifelong treatment?

A

not necessarily - long term studies have shown that successful antiseizure medicaiton withdrawal may occur after a seizure free period of 2-5 years

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4
Q

Risk factors for seizure recurrence

A
  • < 2 years seizure free
  • Onset of seizure after age 12 * History of atypical febrile seizures
  • 2 – 6 years before good seizure control in treatment
  • Significant number of seizures (> 30) before control achieved
  • Partial seizures (which is the most common type)
  • Abnormal EEG throughout treatment
  • Organic neurological disorder – traumatic brain injury, dementia
  • Withdrawal of phenytoin or valproate
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5
Q

Drug-resistant epilepsy

A

defined as failure of at least two trials of antiseizure meds of adequate dose and duration

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6
Q

Possible reasons for treatment failure

A

failure to reach the CNS target
alteration of drug targets in the CNS
drugs missing the real target

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7
Q

Management of drug-resistant epilepsy

A

rule out pseudo-resistance - wrong drug or diagnosis
combination therapy
electrical/surgical intervention

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8
Q

Status epilepticus

A

continuous seizure activity lasting 5 (five) minutes or more, or two or more discrete seizures with incomplete recovery between seizures
■ Intravenous drug therapy commonly used in this situation

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9
Q

Possible drug therapy for status epilepticus

A

benzodiazepines, most commonly lorazepam or midazolam (IV)
initial tx phase (5-20 min): IV lorazepam or midazolam
2nd tx phase (20-40 min): IV fosphenytoin, IV valproic acid, IV levetiracetam

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10
Q

Phenytoin/fosphenytoin requires

A

cardiac monitoring, may also cause a local reaction called “purple glove syndrome”

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11
Q

Fosphenytoin equivalent to

A

20 mg PE (phenytoin equivalents)

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12
Q

Oral phenytoin dosing considerations

A

MUST obtain both phenytoin serum concentration and serum albumin in the same blood draw

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13
Q

Oral phenytoin therapeutic serum concentration

A

10-20 mcg/mL

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14
Q

Valproate IV to PO conversion

A

1:1 mg/mg
IV loading dose: 15-30 mg/kg

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15
Q

Valproate desired serum concentration

A

80 mcg/mL (range 50-125 mcg/mL)

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16
Q

1A2 inducer

A

carbamazepine
phenobarbital
phenytoin

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17
Q

2C9 inducer

A

carbamazepine
phenobarbital
phenytoin

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18
Q

3A4 inducer

A

carbamazepine
phenobarbital
phenytoin
lamotrigine
oxcarbazepine
topiramate

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19
Q

UGT inhibitor

A

valproate

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20
Q

Lamotrigine warning

A

Boxed warning for Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis – lamotrigine is a UGT substrate, high initial serum concentrations associated with SJS/TEN – specific dosing based on concomitant drug therapy with UGT inducers or inhibitors

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21
Q

Lamotrigine with UGT inhibitor (valproate)

A

25 mg every other day x 14 days
25 mg once daily x 14 days
50 mg once daily x 7 days
100 mg once daily

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22
Q

Lamotrigine w/o concomitant UGT drug interactions

A

25 mg once daily x 14 days
50 mg once daily x 14 days
100 mg once daily x 7 days
200 mg once daily

23
Q

Lamotrigine with UGT inducers (carbamazepine, phenytoin)

A

50 mg once daily x 14 days
100 mg once daily x 14 days
200 mg once daily x 7 days
400 mg once daily

24
Q

Anticonvulsant hypersensitivity syndrome

A

Strong correlation for positive
HLA-B1502 allele and AHS
in patients of Asian descent
Positive HLA-A3101 in those of Northern European and Asian descent may confer similar risk
Black box warning - genetic screen for HLA-B*1502 allele prior to initiating carbamazepine or like derivatives (oxcarbazepine, eslicarbazepine)
Patients with positive allele should not be treated with carbamazepine or like derivatives unless benefit clearly outweighs risk

25
Q

DRESS syndrome

A

Potentially life-threatening – estimated mortality rate of 10%
Generally, occurs 2 – 6 weeks after initiation of drug therapy
Associated with carbamazepine, cenobamate, lamotrigine, phenobarbital, phenytoin, valproate, zonisamide
Increased risk in patients who are positive for the HLA-A*3101 allele (usually of Asian or Northern European descent)

26
Q

Antiseizure Drug
Withdrawal Syndrome

A

Associated with abrupt discontinuation of antiseizure medication therapy
May cause recurrence of seizures, doses of antiseizure medication should always be tapered for discontinuation

27
Q

Antiseizure drug therapy in pregnancy

A

Drug serum concentrations may be altered in pregnancy due to changes in volume of distribution
Valproate is not recommended in pregnancy; causes neural tube
defects and is associated with a decreased IQ in the offspring
Many antiseizure drugs are known teratogenic risks – carbamazepine, clonazepam, fosphenytoin, phenobarbital, phenytoin, primidone, topiramate – patient counseling for people of child-bearing age should include education about these risks and contraceptive use (keep in mind OC drug interactions)
Supplemental folic acid (5 mg daily) should be considered during pregnancy
infant should receive vitamin K 1 mg IM at birth to decrease risk of hemorrhagic disease

28
Q

Contraceptive drug interactions

A

mediated by P450 3A4 induction
■ This interaction can be minimized by using higher-dose estrogen contraceptives – warning for increased thromboembolism
■ Can use progestin-only contraceptives – depot formulation
– IUDs are also recommended
■ Estrogen can significantly decrease lamotrigine serum concentration (50%) and lamotrigine decreases estrogen concentrations

29
Q

Cardiovascular Adverse Effects

A

Arrhythmia: lamotrigine
heart block: lacosamide
arrhthmia: phenytoin/fosphenytoin
valvular heart disease: fenfluramine
PR interval changes: lacosamide, pregabalin

30
Q

Electrolyte abnormalities

A

Carbamazepine/eslicarbazepine/oxcarbazepine – hyponatremia, syndrome of inappropriate antidiuretic hormone (SIADH)

31
Q

Metabolic acidosis

A

zonisamide - metabolic acidosis, renal caniculi
Topiramate – decreased serum bicarbonate leading to metabolic acidosis; nephrolithiasis – monitor serum bicarbonate (is also a carbonic anhydrase inhibitor); also associated with decreased sweating, heat intolerance, and oligohydrosis

32
Q

Mineral metabolism (bone loss)

A

Phenytoin – Altered vitamin D metabolism and decreased calcium concentrations leading to osteoporosis with long-term use

33
Q

Psychiatric Side Effects of Antiseizure Medications: perampanel

A

Boxed warning: dose-related serious and/or life-threatening neuropsychiatric events (use with caution with pre-existing psychosis)

34
Q

Psychiatric Side Effects of Antiseizure Medications: levetiracetam

A

Psychosis, suicidal thoughts/
behaviors, unusual mood
changes, worsening depression (most often seen in children and adolescents)

35
Q

Psychiatric Side Effects of Antiseizure Medications: valproate

A

Acute mental status changes related to hyperammonemia; differentiate from sedation side effect
valproate interferes with Kreb’s cycle, causes elevated blood ammonia, carnitine supplementation needed

36
Q

Psychiatric Side Effects of Antiseizure Medications: topiramate

A

Associated with cognitive dysfunction if the dose is increased too rapidly, use a slow dose titration

37
Q

Visual Abnormalities: topiramate

A

post-marketing warning for vision loss, myopia, retinal detachment

38
Q

Visual Abnormalities: vigabatrin

A

is contraindicated in patients who have other risk factors for irreversible vision loss.

39
Q

FDA safety and warning: gabapentin and pregabalin respiratory depression

A

Take-away: Evaluate the appropriateness of gabapentin or pregabalin use and risk for respiratory depression in a patient who is taking other CNS depressants, has pulmonary disease, or is elderly
can increase risk of overdose with other CNS depressant

40
Q

Clinical pearls -mazepines

A

Carbamazepine: strong
P450 (1A2, 2C9, 2C19,
3A4) and p-glycoprotein inducer (induces own metabolism)
Oxcarbazepine induces 3A4
Carbamazepine, Oxcarbazepine, Eslicarbazepine: hyponatremia

41
Q

Clinical pearls: valproate

A

Valproate can cause thrombocytopenia – monitor CBC/platelets; can cause PCOS, weight gain, sedation

42
Q

Clinical pearls: topiramate and zonisamide

A

Topiramate and Zonisamide:
weight loss, oligohydrosis, nephrolithiasis
Zonisamide is contraindicated if there is a sulfa allergy

43
Q

Clinical pearls: phenytoin

A

Phenytoin can cause
gingival hyperplasia and
hirsutism
Phenytoin absorption is decreased when given with enteral feedings, hold feedings 1 – 2 hours before and after administration

44
Q

Clinical pearls: gabapentin and pregabalin

A

Gabapentin and pregabalin are renally eliminated, decrease dose in with renal impairment

45
Q

Clinical pearls: lamotrigine

A

Lamotrigine has been
associated with
arrhythmia in people with
underlying cardiac
conditions

46
Q

Medical marijuana cannabidiol

A

can help to control seizures, especially those refractory to current AED meds
lennox-gastaut syndrome
dravet syndrome

47
Q

Lennox-gastaut syndrome

A

multiple seizure types that develop in childhood, usually accompanied by intellectual disability, sometimes responsive to combination of some AEDs

48
Q

Dravet syndrome

A

rare genetic epileptic encephalopathy with normal childhood development until seizures begin in 1st year of life leading to multiple seizure types and developmental disability

49
Q

Epidiolex® - cannabidiol oral solution

A

Indicated for Dravet Syndrome and Lennox
Gastaut Syndrome

50
Q

Everolimus only indicated for

A

tuberous sclerosis complex (TSC)-associated partial-onset seizures

51
Q

The ketogenic diet

A

3:1 or 4:1 fats:carbs/proteins
Side Effects: hyperlipidemia (reversible upon d/c of diet), weight loss, constipation, kidney stones, decreased bone mass/growth
Adults seem to respond only while on the diet, the effects in children may continue after the diet is discontinued.

52
Q

Depression in epilepsy

A

All antiseizure drugs carry a warning for increased risk of suicidal thinking and/or behaviors during treatment
Antidepressants also carry a warning for increased risk of suicidal thinking and behaviors during treatment in patients < 24 years of age
Use of bupropion should be avoided in patients with uncontrolled seizure disorders, as it can increase the risk of seizures and seizure frequency

53
Q

Depression is a common

A

co-morbidity

PHRM 845 Module #1 (50 decks)

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