Anticonvulsants – Hydontoins

Name of the Hydontoins Drugs

• Ethotoin
• Felbamate
• Phenytoin

1.ETHOTOIN

Mechanism of Action:

Exerts an antiepileptic effect w/o causing general CNS depression. Mechanism of action probably similar to phenytoin but less effective & less toxic than phenytoin

Indications:

• To treat tonic-clonic seizures
• simple or complex partial seizures as initial or adjunct therapy, or when other drugs are ineffective

Cautions & Contraindications:

• Hematologic disorders
• Hepatic dysfunction
• Hypersensitivity to ethotoin, phenytoin, other hydantoins, or their components

Metabolism & Half- life:

• Half-Life: 3-9 hr
• Metabolism: by liver 
• Excretion: urine, feces

Drug Interactions:

• Acetaminophen: increased risk of hepatotoxicity with long-term acetaminophen use
• Amiodarone: possibly increased blood ethotoin level and risk of toxicity
• Bupropion, clozapine, MAO inhibitors,pimozide, thioxanthenes: possibly lowered seizure threshold and decreased therapeutic effects of ethotoin; possibly intensified CNS depressant effects of these drugs.

Side- Effects:

• CNS: Clumsiness, confusion, drowsiness, excitement, peripheral neuropathy, sedation, slurred speech, stuttering, suicidal ideation, tremor
• Eye & ENT: Nystagmus
• GI: Constipation, diarrhea, nausea, vomiting
• HEME: Agranulocytosis, leukopenia, thrombocytopenia
• SKIN: Rash, Stevens-Johnson syndrome, toxic epidermal necrolysis
• Other: Lymphadenopathy, systemic lupus erythematosus

  Nursing Considerations

• Obtain CBC and differential before treatment and monthly for first few months of ethotoin therapy, as ordered.
• Ethotoin shouldn’t be stopped abruptly because of risk of status epilepticus. Plan to reduce dosage gradually or substitute another drug, as prescribed.
• Monitor patient for signs and symptoms of infection or unusual bleeding because ethotoin may cause hematologic toxicity.
• Because of ethotoin’s potential for hepatotoxicity, monitor liver function test results and expect drug to be discontinued if test results are abnormal.
• Notify prescriber immediately and expect ethotoin to be stopped and replaced with another drug if patient has decreased blood counts, enlarged lymph nodes, or rash.
• Be aware that ethotoin may be substituted for phenytoin without loss of seizure control if patient develops severe gingival hyperplasia or other adverse reactions.
• Expect ethotoin dosage to be 4 to 6 times greater than phenytoin dosage.
• Institute and maintain seizure precautions according to facility protocol.
• Monitor patient closely for evidence of suicidal thinking or behavior, especially when therapy starts or dosage changes

Patient teaching

• Instruct patient to take ethotoin exactly as prescribed and not to stop it abruptly.
• Advise patient to take drug with food to enhance absorption and reduce adverse GI effects.
• Advise patient to report easy bruising, epistaxis, fever, malaise, petechiae, or sore throat to prescriber immediately.
• Instruct patient to keep medical appointments to monitor drug effectiveness and check for adverse reactions. Explain the need for periodic laboratory tests.
• Urge patient to avoid alcohol during ethotoin therapy.
• Caution patient to avoid hazardous activities until drug’s adverse effects are known.
• Encourage patient to wear or carry medical identification indicating his diagnosis and drug therapy.
• Urge caregivers to watch patient closely for evidence of suicidal tendencies, especially when therapy starts or dosage changes, and to report any concerns immediately to prescriber.

2.FELBAMATE

Mechanism of Action

May exert anticonvulsant effects by antagonizing the amino acid glycine. When glycine binds to N-methyl-D-aspartate

(NMDA) receptors in the CNS, the frequency at which receptor-gated calcium ion channels open is increased—an

important factor in initiating seizures. Felbamate may raise the seizure threshold by blocking NMDA receptors so glycine can’t bind to them.

Indications:

• Adults: Monotherapy or adjunctive therapy in the treatment of partial seizures, with and without generalization.
• Children: Adjunctive therapy in the treatment of partial and generalized seizures associated with Lennox-Gastaut syndrome.

Cautions & Contraindications:

• Hepatic dysfunction
• history of blood dyscrasias
• hypersensitivity to felbamate other carbamates, or their components

Cautions

• Increased risk of suicidal behavior reported with anticonvulsant use; monitor patients for changes in behavior that might indicate suicidal behavior
• Associated with increased incidence of aplastic anemia and acute hepatic failure, use only when alternative therapy is unsuitable, and benefits outweigh risks
• Use caution in renal impairment
• Not for use as first-line therapy in epilepsy; for use when benefits outweigh risks

Metabolism and Half- Life:

• Half-Life: 20-23 hr
• Peak Plasma: 17-49 mcg/mL (dose-dependent)
• Metabolism: Liver
• Excretion: Urine (80-90%)

Drug Interactions:

• Carbamazepine: decreased blood carbamazepine level and increased felbamate clearance, resulting in decreased blood felbamate level
• Fosphenytoin, phenytoin: increased blood phenytoin level and increased felbamate clearance, resulting in decreased blood felbamate level
• Oral contraceptives: possibly decreased effectiveness of oral contraceptives
• Phenobarbital: decreased blood felbamate level, increased blood phenobarbital level and risk of adverse effects
• Valproic acid: increased blood valproic acid level and increased risk of adverse effects

Side- Effects:

• Heartburn​
• Vomiting​
• Constipation​
• Diarrhea​
• Weight loss​
• Difficulty falling asleep or staying asleep​
• Nervousness​
• Drowsiness​
• Swelling of the face​
• Runny nose​
• Differences in menstrual bleeding​

  Nursing Considerations

• Check liver function test results before starting felbamate, and expect to check results every 1 to 2 weeks during treatment. Notify prescriber immediately and expect to stop drug if results are abnormal.
• Plan to taper dosage by one-third every 4 to 5 days as prescribed. If patient receives adequate amounts of other anticonvulsant drugs, felbamate may be stopped without tapering, if needed.
• Assess for signs of aplastic anemia and bone marrow depression. Signs may not appear until several months after therapy begins. Expect to stop felbamate if bone marrow depression develops.
• If patient receives adjunctive therapy, expect adverse reactions to resolve as other anticonvulsant dosages decrease.
• Monitor patient closely for evidence of suicidal thinking or behavior, especially when therapy starts or dosage changes.

Patient teaching

• Direct patient to shake suspension before using and to use a calibrated spoon or container to measure each dose.
• Instruct patient to store oral suspension and tablets at room temperature.
• Because drug may cause photosensitivity, urge patient to protect skin from sun and to avoid sunlamps and tanning booths.
• Explain that dizziness and drowsiness may occur. Advise her to avoid hazardous activities until drug’s CNS effects are known.
• Warn patient not to stop drug abruptly.
• Advise patient to return for ordered liver function tests and to report yellow skin or eyes and dark urine to prescriber.
• Instruct patient to tell prescriber if she experiences bleeding, infection, or fatigue.
• Advise patient to carry medical identification that indicates condition and therapy.
• Because felbamate decreases oral contraceptive effectiveness, discuss alternate contraceptive methods.
• Urge caregivers to watch patient closely for evidence of suicidal tendencies, especially when therapy starts or dosage changes, and to report any concerns immediately.

3.PHENYTOIN

Mechanism of Action:

Stabilizes neuronal membranes in motor cortex. Decreases influx of sodium during generation of nerve impulses. Therapeutic Effect: Decreases seizure activity

Indications:

• Status epilepticus
• Generalized tonic-clonic (grandmal) and complex partial (psychomotor, temporal lobe) seizures
• To prevent seizures during neurosurgery
• Off-label uses
• Arrhythmias
• Severe preeclampsia
• Trigeminal neuralgia
• Recessive dystrophic epidermolysis bullosa, junctional epidermolysis bullosa

Cautions& Contraindications:

• Hypersensitivity to phenytoin, other hydantoins.
• Concurrent use of delavirdine.
• History of acute phenytoin therapy–induced hepatotoxicity.
• IV (additional): Second- and thirddegree AV block, sinoatrial block, sinus bradycardia, Adams-Stokes syndrome.

Cautions: Porphyria, diabetes, renal/ hepatic impairment, pts at increased risk of suicidal behavior/thoughts, elderly/ debilitated pts, low serum albumin, cardiac disease, hypothyroidism, pts of Asian descent.

Metabolism and Half- Life:

Slowly, variably absorbed after PO administration. Protein binding: 90%–95%. Widely distributed. Metabolized in liver. Primarily excreted in urine. Not removed by hemodialysis. Half-life: 7–42 hrs.

Drug Interactions:

• Alcohol, other CNS depressants may increase CNS depression.
• Amiodarone, cimetidine, isoniazid, sulfonamides may increase concentration/effects, risk of toxicity.
• May decrease effects of glucocorticoids, oral contraceptives.
• Lidocaine, propranolol may increase cardiac depressant effects.

Side – Effects:

• Drowsiness
• Lethargy
• Confusion
• Slurred speech
• Irritability
• Gingival hyperplasia
• Hypersensitivity reaction (fever, rash, lymphadenopathy)
• Constipation
• Dizziness
• Nausea
• Occasional: headache, hirsutism, coarsening of facial features, insomnia, muscle twitching.

Nursing Considerations

Baseline assessment

• Anticonvulsant: Review history of seizure disorder (intensity, frequency, duration, LOC). Initiate seizure precautions.
• LFT, CBC should be performed before beginning therapy and periodically during therapy.
• Repeat CBC 2 wks following initiation of therapy and 2 weeks following administration of maintenance dose.

 Intervention/evaluation

• Observe frequently for recurrence of seizure activity.
• Monitor ECG for cardiac arrhythmia.
• Assess for clinical improvement (decrease in intensity/frequency of seizures).
• Monitor for signs/symptoms of depression, suicidal tendencies, unusual behavior.
• Monitor CBC with differential, renal function, LFT, B/P (with IV use).
• Assist with ambulation if drowsiness, lethargy occurs.
• Monitor for suicidal ideation or behaviors.
• Monitor for therapeutic serum level (10–20 mcg/mL). Therapeutic serum level: 10–20 mcg/ mL; toxic serum level: greater than 20 mcg/mL. Free unbound levels: Therapeutic: 1–2 mcg/mL; toxic: more than 2 mcg/mL.

Patient/family teaching

• Pain may occur with IV injection.
• To prevent gingival hyperplasia (bleeding, tenderness, swelling of gums), maintain good oral hygiene, gum massage, regular dental visits.
• Serum levels should be performed every month for 1 yr after maintenance dose is established and every 3 months thereafter.
• Report sore throat, fever, glandular swelling, skin reaction (hematologic toxicity).
• Drowsiness usually diminishes with continued therapy.
• Avoid tasks that require alertness, motor skills until response to drug is established.
• Do not abruptly withdraw medication after long-term use (may precipitate seizures).
• Strict maintenance of drug therapy is essential for seizure control, arrhythmias.
• Avoid alcohol.
• Report changes in behavior, thoughts of suicide.

REFERENCES

1. Robert Kizior, Keith Hodgson, Saunders Nursing Drug handbook,1st edition 2024, Elsevier Publications. ISBN-9780443116070
2. McGraw Hill- Drug Handbook, Seventh Edition, 2013, McGraw Hill Education Publications,9780071799430.
3. April Hazard, Cynthia Sanoski, Davi’s Drug Guide for Nurses -Sixteenth Edition 2019, FA Davis Company Publications,9780803669451.
4. Jones and Bartlet, Pharmacology for Nurses, Second Edition, 2020, Jones and Bartlet Learning Publications, ISBN 9781284141986.
5. Nursebro.com, Search – Nursebro

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