Prescribing Antiepileptic Drugs and Termination of Status Epilepticus

Flashcards covering the key aspects of prescribing antiepileptic drugs and the management of status epilepticus, based on the lecture notes.

What is epilepsy?

Epilepsy is defined as a brain disorder characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition.

What are the management options for epilepsy?

Management of epilepsy includes Pharmacotherapy, Non-pharmacologic therapy (ketogenic diet and vagal nerve stimulation), and Surgical options.

What is the goal of pharmacotherapy for epileptic seizures?

The goal of treatment in patients with epileptic seizures is to achieve a seizure-free status without adverse drug effects.

Why is monotherapy desirable in treating epilepsy?

Monotherapy is desirable because it decreases the likelihood of adverse effects and avoids drug interactions. It may also be less expensive.

When is polytherapy considered in treating epilepsy?

Polytherapy is considered when another drug known to have a beneficial effect on the type of epilepsy is added to the drug that does not achieve full seizure control. It is used in refractory forms of epilepsy.

Briefly describe Antiepileptic therapy.

The introduction of the drug into the therapy is carried out gradually, by graduating the dose to the maintenance dose, which is individual for each patient. AEL therapy is usually chronic (over many years) and Withdrawal of the drug must also be gradual, over several months

What is the relapse rate for seizures in adults after discontinuing AEDs?

The relapse rate for seizures in adults is about 40-50%; for children, it is about 25%.

How should AEDs be discontinued, according to some authors?

Some authors recommend that all AEDs, except primidone, phenobarbital, and benzodiazepines, be gradually discontinued over 6-10 weeks if they were used for a long period, while primidone, phenobarbital, and benzodiazepines should be discontinued over 10-16 weeks.

What factors should be considered when choosing an AEL drug?

The choice of drug is primarily based on the type of epileptic seizure or epileptic syndrome, efficiency and adverse effects of the drug, patient characteristics (age, BW, gender, comorbidities, liver and kidney function).

Name some types of generalized epileptic seizures.

tonic-clonic seizures, clonic seizures, tonic seizures, myoclonic seizures Absence (petit mal)

What are the two main types of absence seizures?

Typical absence and Atypical absence

What is the first-line therapy for typical absence seizures?

First-line therapy for typical absence is monotherapy with Ethosuximide or Valproate, or a combination of the two.

What drugs should not be used as AEL for typical absence?

Do not use carbamazepine, pregabalin or tiagabine, because these drugs may exacerbate absence seizures

What is important to know when prescribing ethosuximide?

It is effective only against absence seizures, therapeutic range: 40-100 mg/L, the major side effects are nausea, vomiting and anorexia. Blood levels should be measured 1-3 weeks after starting ethosuximide. Drug-induced immune thrombocytopenia (DITP) is reported

What is important to know when prescribing valproate?

Valproate is effective against all known seizure types, therapeutic range: 50-100 mg/L. Side effects include gastrointestinal complaints, pancreatitis, weight gain, thrombocytopenia, etc. It has a high potential for interactions with other AEDs.

What medicines are commonly used to treat atypical absence seizures?

Medicines commonly used to treat atypical absence are Clonazepam, Valproate, or Felbamate.

What should be monitored frequently during the administration of valproic acid?

Liver function (transaminase level in the serum) must be monitored frequently during the administration of valproic acid (once a month during the first six months of therapy).

What is important to know when prescribing clonazepam?

Clonazepam is a long-acting and high-potency benzodiazepine, therapeutic range: 0.02-0.08 mg/L. Common side effects include lethargy, fatigue, sedation, drowsiness, and motor impairment.

What is important to know when prescribing felbamate?

Felbamate is used as a monotherapy or as adjunctive therapy, therapeutic range: 30-60 mg/L. Common side effects include drowsiness, insomnia, anorexia, nausea, dizziness, headache, somnolence. Use is limited by severe, life-threatening reactions.

What is the first-choice drug for tonic-clonic and myoclonic seizures?

The drug of first choice is valproate, due to the multiple mechanisms through which it acts and the best results in clinical studies.

What is important to know when prescribing lamotrigine?

Lamotrigine is an antiepileptic drug with a very broad spectrum of activity, therapeutic range: 3-14mg/L. It must be introduced gradually into the therapy to avoid Stevens-Johnson syndrome. It has a high potential for PK interaction with other AEDs.

What is important to know when prescribing levetiracetam?

Levetiracetam is used as monotherapy or as adjunctive therapy, has a rapid onset of action and is well tolerated. A dose reduction in patients with compromised renal function must be individualised according to creatinine clearance.

What is important to know when prescribing topiramate?

Topiramate is used as monotherapy or as adjunctive therapy, therapeutic range: 5-20mg/L. Contraindications include within 6 hours of alcohol intake and patients with metabolic acidosis taking metformin concomitantly. It reduces sweating, so in the summer it can lead to hyperthermia.

What can be used for generalized tonic-clonic seizures?

Phenytoin and phenobarbital can also be used for generalized tonic-clonic seizures, but they have many side effects. Newer antiepileptic drugs (lamotrigine, topiramate and levetiracetam) have the same effectiveness but less side effects

What can be used for tonic and atonic seizures?

Tonic and atonic seizures can be most effectively prevented by valproate (alone or in combination with a benzodiazepine)

What is important to know when prescribing rufinamide?

The drug is available as tablets and oral suspension, has a low potential for drug-drug interactions. Most common side effects: fatigue, nausea, vomiting, decreased appetite… Contraindications: Familial short QT syndrome.

What are the two types of seizures based on consciousness?

simple partial (consciousness is not lost) and complex partial (there is a disturbance of consciousness)

What class of drugs is succinimide?

antiepileptics

What factors should guide the choice of antiepileptic drugs for simple partial epilepsies?

The choice should be made based on the profile of the side effects of individual antiepileptics and the characteristics of the patient himself.

Which drugs are used as monotherapy for partial seizures with secondary generalization?

Carbamazepine, Oxcarbazepine, Phenytoin, Topiramate, Lamotrigine, or Levetiracetam.

What is important to know when prescribing carbamazepine?

Carbamazepine is available as tablets, capsule, oral suspension, IV solution, therapeutic range: 4-12mg/L. It is a strong inducer of the CYP3A4 isoenzyme. Aplastic anemia and agranulocytosis are reported. Stevens- Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) in patients of Asian origins (genetic testing recommended)

What is important to know when prescribing zonisamide?

Zonisamide is used as additional therapy for partial onset epilepsies, therapeutic range: 10-38mg/L. It can cause confusion, higher frequency of renal calculus, and oligohidrosis in children and metabolic acidosis. It is primarily metabolized through CYP 3A4.

What is important to know when prescribing lacosamide?

Lacosamide is used as monotherapy or adjunctive therapy for partial onset seizures. Patients with renal or hepatic impairment who are taking strong CYP3A4 and CYP2C9 inhibitors may have a significant increase in exposure to lacosamide. It may cause drug reaction with eosinophilia and systemic symptoms (DRESS).

What is important to know when prescribing pregabalin?

Pregabalin is indicated as adjunctive therapy. Dose reduction in patients with compromised renal function must be individualised according to creatinine clearance. Creatine kinase elevations have been associated with treatment (monitor for symptoms).

What is important to know when prescribing cenobamate?

Cenobamate is indicated both as monotherapy or adjunctive therapy. Common side effects: somnolence, dizziness, fatigue, double vision, serum potassium increased. Cenobamate has the most interactions with other drugs.

What antiepileptic drug should not be used for the treatment of complex focal onset seizure?

ethosuximide

How do the doses of AEDs differ in neonates/children versus elderly patients?

Neonates and children require similar loading doses per kilogram of body weight, but they tend to metabolize the drugs faster than adults. Elderly patients need lower initial and maintenance doses due to slowed hepatic metabolism, decreased renal clearance, and decreased volumes of distribution.

Which AEDs can decrease the efficacy of oral contraceptive pills?

AEDs that induce hepatic enzymes, such as carbamazepine, phenytoin, phenobarbital or primidone, and also lamotrigine, topiramate, oxcarbazepine, and cenobamate, decrease the efficacy of oral contraceptive pills.

What is recommended for women of childbearing age taking AEDs?

They should take folic acid, at least 0.4 mg per day, to decrease the rate of neural-tube malformations in the fetus. Switching medications during pregnancy is not recommended.

Which antiepileptic drug is the least teratogenic?

lamotrigine

What is important to know when prescribing gabapentin?

Gabapentin is used as adjunctive therapy in the treatment of partial seizures. Important benefits: no interaction with valproate, lithium, and carbamazepine. Dose reduction in patients with compromised renal function must be individualised according to creatinine clearance.

What is teratogenicity?

the ability to cause defects in a developing fetus

Why should prophylactic vitamin K be given to pregnant and newborn mothers taking phentotoin, carbamazepine, or phenobarbital

When the mother takes phenytoin, carbamazepine or phenobarbital, there is an increased risk of bleeding in the newborn

Which AEDs are useful in patients with hepatic failure?

Gabapentin, pregabalin, levetiracetam, and lacosamide are excreted mostly by means of renal clearance, and their doses can be adjusted for renal insufficiency. Lamotrigine, which is metabolized by means of glucuronidation, is also used in some patients with hepatic insufficiency.

Which AEDs have been associated with acute hepatic injury?

valproic acid and felbamate

What is status epilepticus?

Status epilepticus is a condition in which we have two or more consecutive epileptic seizures without full recovery of consciousness in between, or one seizure that lasts longer than 30 minutes.

Why is status epilepticus considered a neurologic emergency?

It is considered a neurologic emergency due to its significant morbidity and mortality, and aggressive therapy is necessary for any attack that lasts longer than 5 minutes.

What is refractory status epilepticus?

A seizure that meets the criteria for status epilepticus and does not respond to the therapy of choice (second-line therapy) is called a refractory status epilepticus.

What is super-refractory status epilepticus?

If refractory status continues even after 24 hours from the introduction of the patient into anesthesia, such a condition is called super-refractory status epilepticus.

What is the prognosis factors of Status Epilepticus?

Morbidity and mortality: is proportional to the duration of the attack response to therapy also decreases with duration depends on the cause of status epilepticus it depends on the age of the patient

What is Nonconvulsive and Generalized convulsive?

Nonconvulsive status epilepticus is a permanent state of impaired consciousness, or motor or sensory attacks without impaired consciousness. Generalized convulsive status epilepticus is characterized by generalized motor convulsions with the involvement of the entire brain

What are the consequences of Status Epilepticus?

Status epilepticus leads to serious disruption of the homeostasis of the body, which is manifested by lactic acidosis, hypoglycemia, hypoxia, elevated temperature, rhabdomyolysis, and myoglobinuria.

What are the treatment steps for Status Epilepticus?

Assessment of CAB, Placement of venous line and urinary catheter, Application of medicines

What are the first-line medicines for Status Epilepticus?

Benzodiazepines, such as intravenous lorazepam, diazepam, or midazolam.

What are some second-line medicines for Status Epilepticus?

Intravenous fos/phenytoin or valproic acid

What should be treated with additional medication?

Be aware of the possible underlying causes of status epilepticus, including hypoglycaemia, eclampsia and alcohol withdrawal

Why is Lorazepam preferred over diazepam?

Lorazepam is less liposoluble than diazepam, so the distribution of the drug is less pronounced, and its effect lasts longer (6-12 hours)

Why is Fosphenytoin preferred?

Fosphenytoin is preferable, as it provides the advantage of a potentially rapid rate of administration with less risk of venous irritation ( to avoid the risk of purple-glove syndrome with phenytoin)

What agent is generally used after phenytoin or fosphenytoin fails?

Phenobarbital

How can Antiepileptics be divided into large groups?

Blockers of repetitive activation of the sodium channel, T-calcium channel blockers: and N- and L-calcium channel blockers