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Antiepileptics: Nursing Pharmacology

Notes

Notes

ANTIEPILEPTICS, PART 1
DRUG NAME
phenytoin (Dilantin), fosphenytoin (Cerebyx), carbamazepine (Tegretol), valproic acid (Depacon), sodium valproate (Depakote), lamotrigine (Lamictal)
ethosuximide (Zarontin), levetiracetam (Keppra)
CLASS
Sodium channel blockers
Calcium channel blockers
MECHANISM OF ACTION
Block voltage-gated Na+ channels; inhibition of action potentials in excitatory neurons; ↓ seizure activity
Block voltage-gated Ca2+ channels; inhibition of action potentials in excitatory neurons; ↓ seizure activity
INDICATIONS
  • Epilepsy, generalized seizures, partial seizures
  • Mood disorders
ROUTE(S) OF ADMINISTRATION
  • Phenytoin: PO, IV
  • Fosphenytoin: IV, IM
  • Carbamazepine: PO, IV
  • Valproate: PO, IV
  • Lamotrigine: PO
  • Ethosuximide: PO
  • Levetiracetam: PO, IV
SIDE EFFECTS
Phenytoin, fosphenytoin
  • Headaches, dizziness, visual disturbances, hypersensitivity reactions (SJS, TEN, DRESS), hepatotoxicity, impaired metabolism of vitamin D, decreased absorption of folic acid and vitamin B12, blood dyscrasias, suicidal thoughts
  • Boxed warning: rapid IV administration can result in hypotension and cardiac arrhythmias

Carbamazepine
  • Pancreatitis, hepatotoxicity, renal dysfunction, hypertension, AV block
  • Boxed warning: SJS, TEN, DRESS, bone marrow depression

Valproate
  • Gastrointestinal problems, thrombocytopenia, leukopenia, DRESS, suicidal thoughts, CNS depression, coma
  • Boxed warning: pancreatitis, hepatotoxicity, fetal toxicity

Lamotrigine
  • Headache, dizziness, dysmenorrhea; seizures, suicidal thoughts, disseminated intravascular coagulation, leukopenia, thrombocytopenia
  • Boxed warning: SJS, TEN
Ethosuximide
  • Gastrointestinal problems, fatigue, headache, pruritus, blood dyscrasias, DRESS

Levetiracetam
  • Suicidal thoughts, SJS, TEN, hepatitis
CONTRAINDICATIONS AND CAUTIONS
Phenytoin
  • Pregnancy, sinus bradycardia, heart block, Adams-Stokes syndrome

Carbamazepine
  • Pregnancy, breastfeeding, alcoholism, cardiac, hepatic, or renal disease, children < 6 years
  • Not be administered within 14 days of MAOIs, or concomitantly with non-nucleoside reverse transcriptase inhibitors

Valproate
  • Pregnancy, urea cycle disorders, mitochondrial disease, hepatic disease

Lamotrigine
  • Pregnancy; breastfeeding; severe depression; clients < 16  years, elderly; cardiac, hepatic, or renal disease
Ethosuximide
  • Pregnancy, breastfeeding, hepatic or renal disease

Levetiracetam
  • Pregnancy; breastfeeding; pediatric or elderly clients; cardiac, hepatic, or renal disease
ANTIEPILEPTICS, PART 2
DRUG NAME
vigabatrin (Sabril)
gabapentin (Neurontin, Gralise)
CLASS
GABA inhibitors
GABA analogues
MECHANISM OF ACTION
Prevent GABA reuptake into presynaptic neurons; ↑ GABA concentration in synapse; ↓ seizure activity
Structurally similar to GABA
INDICATIONS
  • Epilepsy, generalized seizures, partial seizures
  • Mood disorders
ROUTE(S) OF ADMINISTRATION
vigabatrin: PO
PO
SIDE EFFECTS
Vigabatrin
  • Dizziness, gastrointestinal problems, weight gain, edema, decreased hemoglobin and hematocrit, peripheral neuropathy, malignant hyperthermia, suicidal thoughts, respiratory depression, pulmonary embolism
  • Boxed warning: visual impairment
  • Depression
  • Amnesia
  • Somnolence
  • Ataxia
  • Blurred vision, nystagmus, diplopia
  • Dry mouth
  • Gastrointestinal problems
  • Pruritus
  • DRESS
  • Leukopenia
CONTRAINDICATIONS AND CAUTIONS
Vigabatrin
  • Pregnancy, breastfeeding, children < 2 years old, elderly clients, hepatic or renal disease, history of psychosis or depression
  • Pregnancy and breastfeeding
  • Children < 3 years old
  • Elderly clients
  • Suicidal thoughts
  • Depression
  • Renal disease
  • Hemodialysis
NURSING CONSIDERATIONS: ANTIEPILEPTICS
ASSESSMENT AND MONITORING
All antiepileptics

Assessment
  • Type, frequency, and duration of seizures
  • Screenings
    • Depression, suicidal thoughts
    • Pregnancy
  • Laboratory test results
    • CBC
    • Liver and renal function tests
  • Diagnostic tests
    • ECG (phenytoin, carbamazepine, or lamotrigine)
    • Baseline vision test (vigabatrin)

Monitoring
  • Mental status, mood, behavior
  • CBC, liver, and renal function
  • Evaluate therapeutic effect: decrease in seizure frequency, severity, and duration
CLIENT EDUCATION
All antiepileptics

  • Purpose of medication
  • Take exactly as prescribed; do not stop abruptly
  • Use reliable contraception while taking an antiepileptic medication
  • Wear medical identification
  • Side effects
    • CNS depression
      • Avoid other CNS depressant medications; alcohol
      • Avoid activities that require alertness
    • Immediately report
      • Increased risk of suicidal behavior; e.g., anxiety, agitation, depression, other changes in their mood or behavior
      • Liver dysfunction; e.g., anorexia nausea, vomiting, and fatigue
      • Blood dyscrasias; e.g., fever, sore throat, pallor, weakness, petechiae, easy bruising
      • Skin changes; development of unusual rash
Sodium channel blockers
GABA inhibitors
Phenytoin
  • Recognize signs of gingival hyperplasia; e.g., sore, swollen gums
  • Maintain dental hygiene, folic acid supplement, regular dentist visits
  • Decrease risk of bone loss: increase dietary calcium and vitamin D; weight-bearing exercises as tolerated
  • Report visual disturbances; e.g., blurred vision, nystagmus, diplopia

Carbamazepine
  • Avoid grapefruit / grapefruit juice
  • Report symptoms of pancreatitis; e.g., upper abdominal pain, nausea, vomiting, anorexia
  • Report symptoms of water retention and hyponatremia; e.g., swelling, weight gain, headache, muscle weakness or cramps

Valproate
  • Report symptoms of pancreatitis; e.g., upper abdominal pain, nausea, vomiting, anorexia
Vigabatrin
  • Vision checks every three months during therapy
  • Report vision changes; e.g., blurred vision, difficulty controlling eye movements, vision loss
  • Report symptoms of peripheral neuropathy; e.g., burning or numbness in toes or feet
Transcript

Antiepileptics, also known as anticonvulsants, are medications primarily used to treat epilepsy, as well as generalized or partial seizures. On rare occasions, these medications can be used to treat mood disorders.

Now, the most commonly used antiepileptics can be subdivided, based on their mechanism of action, into four main groups: sodium channel blockers, calcium channel blockers, GABA inhibitors, and GABA analogues.

In addition, other medications can be used as antiepileptics, including barbiturates like phenobarbital and benzodiazepines like diazepam, which are primarily used as anxiolytics and sedative-hypnotics.

Now, let’s focus on sodium channel blockers first. These medications work by blocking voltage-gated sodium channels, eventually inhibiting excitatory neurons from firing action potentials.

Decreased activity of excitatory neurons results in the reduction and alleviation of seizures. Sodium channel blockers include hydantoins, iminostilbene derivatives, valproate derivatives, and lamotrigine.

First, let’s focus on hydantoins. These medications include phenytoin, which can be administered orally or intravenously; and its prodrug, fosphenytoin, which can be administered intravenously or intramuscularly.

Common side effects of these medications include headaches, dizziness, visual disturbances, such as blurred vision, nystagmus, and diplopia, as well as gingival hyperplasia.

Some clients might experience hypersensitivity reactions like Stevens-Johnson syndrome and toxic epidermal necrolysis, as well as drug reactions with eosinophilia and systemic symptoms or DRESS for short.

In addition, these medications can cause hepatotoxicity, as well as impaired metabolism of vitamin D, which can result in osteomalacia.

Moreover, these medications can impair the absorption of folic acid and vitamin B12; this can lead to hematologic side effects, often referred to as blood dyscrasias, such as agranulocytosis, leukopenia, thrombocytopenia, and anemia.

As a boxed warning, rapid IV administration can result in hypotension and cardiac arrhythmias. Finally, a very important side effect is suicidal thoughts.

As far as contraindications go, phenytoin should be avoided during pregnancy, as well as in clients with sinus bradycardia, heart block, and Adams-Stokes syndrome, which refers to a condition characterized by syncopal episodes caused by cardiac arrhythmias.

The next group of sodium channel blockers covers iminostilbene derivatives, such as carbamazepine, which can be administered orally or intravenously.

Important side effects include pancreatitis, hepatotoxicity, and renal dysfunction which could result in fluid retention and hyponatremia, as well as cardiovascular side effects, such as hypertension and AV block.

In addition, carbamazepine has boxed warnings for severe side effects, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS, as well as bone marrow depression, which can result in blood dyscrasias.

Now, carbamazepine should not be administered within 14 days of monoamine oxidase inhibitors, or concomitantly with non-nucleoside reverse transcriptase inhibitors that are CYP3A4 substrates, such as nefazodone.

Finally carbamazepine is contraindicated during pregnancy, and should be used with caution in clients who are breastfeeding, as well as in those with alcoholism, cardiac, hepatic, or renal disease, and in children younger than 6 years of age.

The next group includes valproate derivative forms, called valproic acid and sodium valproate, which can be administered orally and intravenously.

Now, in addition to working as sodium channel blockers, these medications can increase the concentration of gamma-aminobutyric acid, or GABA for short, which is one of the main inhibitory neurotransmitters in the brain.

Ultimately, this results in decreased seizure activity. The most common side effects are gastrointestinal problems, such as dyspepsia, nausea, vomiting, diarrhea, and constipation.

Some clients might also experience hematologic side effects, like thrombocytopenia and leukopenia; while others can develop DRESS.

In addition, valproate can cause suicidal thoughts, as well as central nervous system depression or even coma. Finally, it’s important to note that valproate has boxed warnings for pancreatitis and hepatotoxicity, as well as regarding fetal toxicity, since valproate may result in congenital malformations, especially neural tube defects.

For that reason, valproate is contraindicated during pregnancy. In addition, it should be avoided in clients with urea cycle disorders, mitochondrial disease, or hepatic disease.

The last sodium channel blocker is lamotrigine, which is taken orally. The most common side effects include headache, dizziness, and dysmenorrhea.

On rare occasions, lamotrigine can also cause more severe side effects, such as suicidal thoughts, and hematologic side effects, including disseminated intravascular coagulation, leukopenia, and thrombocytopenia.

Also, lamotrigine has a boxed warning for causing serious and potentially life-threatening skin rash, as well as Stevens-Johnson syndrome and toxic epidermal necrolysis.

Now, lamotrigine must not be stopped abruptly, since clients may present with uncontrolled seizures. In addition, this medication should be used with caution during pregnancy and breastfeeding, as well as in clients with severe depression, and in clients younger than 16 or elderly.

Finally, precaution should be taken in clients with cardiac disease, such as heart failure or conduction disorders like second or third degree heart block, as well as in clients with hepatic or renal disease.

The next group of antiepileptics is calcium channel blockers. These medications work by blocking voltage-gated calcium channels, subsequently inhibiting excitatory neurons from firing action potentials, and ultimately decreasing seizure activity.

First, let’s start with succinimides, more specifically ethosuximide, which is taken orally. The most common side effects include gastrointestinal problems, such as nausea, vomiting, and diarrhea.

Some clients might also complain of headaches, fatigue, and pruritus; while others might even develop blood dyscrasias or hypersensitivity skin reactions like DRESS.

Finally, these medications should be used with caution during pregnancy and breastfeeding, as well as in clients with hepatic or renal disease.

Another important medication is levetiracetam, which can be administered orally or intravenously. The exact mechanism of action of levetiracetam is not fully understood, but it’s thought to act as a calcium channel blocker.

Important side effects associated with levetiracetam include suicidal thoughts, Stevens-Johnson syndrome, as well as toxic epidermal necrolysis. Some clients can also develop hepatitis.

Finally, this medication is contraindicated in clients who are breastfeeding, and should be used with caution during pregnancy, as well as in pediatric or elderly clients, and those with cardiac, hepatic, or renal disease.

Sources
  1. "Mosby's 2021 Nursing Drug Reference (34e)" Mosby (2021)
  2. "Pharmacology: A Patient-Centered Nursing Process Approach (8e)" Elsevier Health Sciences (2014)
  3. "Focus on Nursing Pharmacology" LWW (2019)
  4. "Saunders Comprehensive Review for the NCLEX-RN Examination (8e)" Saunders (2020)
  5. "Lehne's Pharmacology for Nursing Care" Elsevier Health Sciences (2014)