Chapter 27 Drugs for Seizure Disorders

Oxcarbazepine [Oxtellar XR, Trileptal] (Cont.)

-Adverse effects: Dizziness, drowsiness, double vision, nystagmus, headache, nausea, vomiting, and ataxia -Clinically significant hyponatremia (sodium concentration below 125 mmol/L) -Stevens-Johnson syndrome +Toxic epidermal necrolysis

!!!Epilepsy: Drug Therapy Considerations

-Drug evaluation 1. Antiseizure drug (AED) trial period 2. Dosage adjustment 3. Seizure frequency chart 4. Therapeutic levels 5. Monitoring plasma drug levels 6. Promoting patient adherence 7. Withdrawing antiseizure drugs 8. Suicide risk: Antiseizure drugs

Drug Exemplar: Phenytoin [Dilantin, Phenytek]

-Focal-onset and tonic-clonic seizures -Mechanism of action: Selective inhibition of sodium channels -Varied oral absorption -Half-life: 8 to 60 hours -Therapeutic levels: 10 to 20 mcg/mL -DO NOT STOP ABRUPTLY

Definition of Seizure Disorders

-Group of disorders characterized byexcessive excitability of neurons in the central nervous system -Can produce a variety of symptoms that range from brief periods of unconsciousness to violent convulsions -May also cause problems with learning, memory, and mood

Drug Exemplar: Oxcarbazepine [Oxtellar XR, Trileptal]

-New class of antiseizure medication -Indicated for monotherapy and adjunctive therapy of focal-onset seizures in adults and children -Antiseizure effects: Voltage-sensitive sodium channels in neuronal membranes blocked, hyperexcitable neurons stabilized, and seizures suppressed

Mixed Seizures: Lennox-Gastaut Syndrome

-Severe form of epilepsy that usually develops during the preschool years -Involves developmental delay and a mixture of focal-onset and generalized-onset seizures

Drug Exemplar: Gabapentin [Neurontin, Gralise]

-Therapeutic use: Adjunctive therapy of focal-onset seizures -Off-label use: Neuropathic pain, prophylaxis of migraine, treatment of fibromyalgia, and relief of postmenopausal hot flashes -Adverse reactions +Very well tolerated +Most common side effects: Somnolence, dizziness, ataxia, fatigue, nystagmus, and peripheral edema

Drug Exemplar: Levetiracetam [Keppra]

-Unique agent that is chemically and pharmacologically different from all other antiseizure drugs -IV & PO -Mechanism of action: Unknown -Adverse effects: Mild to moderate -Drug interaction: Does not interact with other antiseizure drugs

Management of Generalized Convulsive Status Epilepticus

1. Continuous series of tonic-clonic seizures that lasts 20 to 30 minutes 2. Goals of treatment -Maintain ventilation -Correct hypoglycemia -Terminate seizures •Benzodiazepine lorazepam is recommended for first-line management •Diazepam, which is also a benzodiazepine, may be used if lorazepam is not readily available -Initiate or continue long-term suppression drugs such as phenytoin [Dilantin] or fosphenytoin [Cerebyx]

Phenytoin Drug interactions

1. Decreases the effects of oral contraceptives, warfarin, and glucocorticoids 2. Increases levels of diazepam, isoniazid, cimetidine, alcohol, and valproic acid 3. Dosing: Highly individualized 4. Administration: With food

Antiseizure Drugs

1. Effects -Suppress discharge of neurons within a seizure focus -Suppress propagation of seizure activity from the focus to other areas of the brain 2. Mechanisms of action -Suppression of sodium influx -Suppression of calcium influx -Antagonism of glutamate -Potentiation of gamma-aminobutyric acid (GABA)

Types of Seizures

1. Focal-onset seizures -Focal aware -Focal impaired awareness -Focal to bilateral tonic-clonic seizures 2. Generalized-onset seizures -Tonic-clonic -Absence -Atonic (slouchy) -Myoclonic (jerky movements) -Status epilepticus -Febrile

Adverse effects Valproate

1. Gastrointestinal effects 2. Hepatotoxicity: Liver failure 3. Pancreatitis 4. Teratogenic effects 5. Hyperammonemia 6. Others

Carbamazepine [Tegretol] Drug-drug and drug-food interactions

1. Hepatic drug-metabolizing enzymes 2. Warfarin 3. Oral contraceptives 4. Phenytoin 5. Phenobarbital 6. Grapefruit juice

Carbamazepine [Tegretol] Adverse effects

1. Neurologic effects: Nystagmus and ataxia 2. Hematologic effects: Leukopenia, anemia, and thrombocytopenia 3. Birth defects 4. Hypo-osmolarity 5. Dermatologic effects: Rash and photosensitivity reactions

Adverse effects Phenobarbital

1. Neuropsychologic effects 2. Dependency 3. Exacerbation of intermittent porphyria 4. Rickets and osteomalacia 5.Nystagmus 6. Ataxia 7. Excessive sleepiness

Phenytoin Adverse effects

1. Nystagmus-lazy eyes 2. Sedation 3. Ataxia: unbalanced muscles movement 4. Diplopia-double vision 5. Cognitive impairment 6. Gingival hyperplasia 7. Skin rash 8. Effects in pregnancy 9. Cardiovascular effects >>Gingival hyperplasia: Swelling, tenderness, and bleeding of the gums: -Gingivectomy -Folic acid (0.5 mg/day) may prevent gum overgrowth -Risk can be minimized by good oral hygiene, including dental flossing and gum massage

Phenobarbital Drug interactions

1. Oral contraceptives 2. Warfarin 3. Central nervous system depressants 4. Valproic acid -Drug withdrawal issues

Drug interactions Valproate

1. Phenobarbital 2. Phenytoin 3. Topiramate 4. Meropenem 5. Imipenem/cilastatin

!!!Goals of Seizure Treatment

1. Reduce seizures to a level that allows the patient to live as normal a life as possible 2. Balance the desire for complete seizure control with acceptable side effects

Therapeutic uses Valproate

1. Seizure disorders 2. Bipolar disorder 3. Migraine

Carbamazepine [Tegretol]

1. Uses -Epilepsy -Bipolar disorder -Trigeminal and glossopharyngeal neuralgias 2. Mechanism of action -Suppresses high-frequency neuronal discharge in and around seizure foci

Phenobarbital

Actions: -Reduces seizures without causing sedation -Anticonvulsant barbiturate -Potentiates the effects of GABA Uses: -Epilepsy (focal-onset and generalized-onset tonic-clonic seizures) Sedation -Induction of sleep

A patient is newly prescribed carbamazepine [Tegretol] for seizure control. It is most important for the nurse to teach the patient to avoid which food? A.Tomatoes B.Grapefruit juice C.Spinach D.Kiwi fruit

B.Grapefruit juice

A patient is prescribed phenytoin [Dilantin] for epileptic seizures. Which of the following is the priority for patient teaching? A.Teach the patient to adjust the dose according to the presence of symptoms. B.Tell the patient to take the medication with meals. C.Inform the patient about the prevention of gingival hyperplasia. D.Teach the patient to avoid the abrupt cessation of treatment.

D.Teach the patient to avoid the abrupt cessation of treatment.

Valproate [Depakote,Depakote ER, Depakote Sprinkles]

Mechanism of action 1. Suppresses high-frequency neuronal firing through the blockade of sodium channels 2. Suppresses calcium influx through T-type calcium channels 3. May augment the inhibitory influence of GABA

Drug Exemplar: Lamotrigine [Lamictal]

Therapeutic use: -Broad spectrum of antiseizure activity -Bipolar disorder Adverse effects: -Dizziness, diplopia, blurred vision, nausea, vomiting, and headache -Severe skin reactions -Aseptic meningitis -Risk for suicide

Classification of Antiseizure Drugs

Two major categories 1. Traditional Antiseizure Drugs •Phenytoin, fosphenytoin, carbamazepine, valproic acid, ethosuximate, phenobarbital, and primidone 2. Newer generation: Total of 15 •Less side effects/ better tolerated •Ex. Oxcarbazepine