Anti epileptic drugs

1. Anti epileptic
drugs
Evaluator: Mr L Anand Presenter: Shruti Shirke
[Asso professor, CON AIIMS BBSR] M.Sc Neuroscience Nursing

2. Definition
• Seizure: the clinical manifestation of an abnormal synchronization and
excessive excitation of a population of cortical neurons
• A transient alteration of behavior due to the disordered and synchronous
firing of populations of brain neurons
• May be Non Epileptic Seizure
• Epilepsy: Disease of lightening
• Epilepsy is a syndrome of two or more unprovoked or recurrent seizures on
more than one occasion
• Manifest as brief episodes (seizure) of loss or disturbance of consciousness,
sensory or psychiatric phenomena with or without characteristic body
movements (convulsions).

3. Antiepileptic Drugs (AEDs)
• A drug which decreases the frequency and/or severity of seizures in
people with epilepsy
• Treats the symptom of seizures, not the underlying epileptic condition
• Goal—maximize quality of life by minimizing seizures and adverse
drug effects
• 75% patients can achieve satisfactory seizure control with medical
therapy.

4. Cellular Mechanisms of Seizure
Generation
• Excitation (too much)
– Ionic‐inward Na+, Ca++ currents
– Neurotransmitter: Glutamate, Aspartate
• Inhibition (too little)
– Ionic‐inward CI‐, outward K+ currents
– Neurotransmitter: GABA

5. Neurotransmitters
• Glutamate:
• Brain’s major excitatory
neurotransmitter
• Two groups of glutamate receptors
– Ionotropic ‐ fast synaptic
transmission
• NMDA, AMPA, kainate
• Gated Ca++ and Na+ channels
– Metabotropic ‐ slow synaptic
transmission
• GABA:
• Major inhibitory neurotransmitter in
the CNS
• Two types of receptors
– GABA-A
• Post‐synaptic
• Linked to CI‐ channel
– GABA-B
• Pre‐synaptic reduction in
calcium influx
• Mediated by K+ currents

6. Basic Mechanisms of AEDs
• Most common ones:
• Modification of ion conductance
• Prolongation of Na+ channel inactivation
• Inhibition of `T` type Ca++ current
• Increase inhibitory (GABAergic) transmission – Cl- Channel.
• Glutamate receptor antagonism (NMDA, AMPA, or kainic acid)

7. Classification of Antiepileptic Drugs

8. Classification of Antiepileptic Drugs

9. Pharmacokinetic principles
• Absorption:
- Essentially complete for all AEDs (except gabapentin)
– Generally slowed by food in stomach (CBZ may be exception)
• Elimination: by metabolism and excretion
– Metabolism/biotransformation — generally hepatic; usually rate‐limiting step
– Excretion — mostly renal
– Changes in metabolism over time
• AED serum concentration:
• Assessing compliance
• To monitor pharmacodynamic and pharmacokinetic interactions
• Most often individual patients define their own “ therapeutic range” for AEDs

10. Adverse Effects (dose‐related)
• Acute dose‐related— usually reversible
• Chronic—reversibility and seriousness vary
• Dizziness , Fatigue , Ataxia, Diplopia, Sedation : all AEDs
• Irritability : Levetiracetam
• Weight loss/anorexia : Topiramate, Zonisamide, Felbamate
• Weight gain : Carbamazepine, Gabapentin, Pregabalin, Valproate

11. Adverse Effects of AEDs: Serious
• Renal stones: Topiramate, Zonisamide
• Anhydrosis, heat stroke: Topiramate
• Acute closed‐angle glaucoma: Topiramate
• Hyponatremia: Carbamazepine, Oxcarbazepine – Used in DI
• PCOD : Valproate
• Aplastic anemia: Valproate, Carbamazepine, Felbamate, Zonisamide,
• Hepatic Failure: Valproate, Felbamate, Lamotrigine, Phenobarbital
• Peripheral vision loss: Vigabatrin
• Rash (SJS, TEN): Phenytoin, Lamotrigine, Zonisamide, Carbamazepine

12. Drug reaction with Eosinophilia and
systemic symptoms (DRESS)
• Life threatening condition typically presents with:
• Fever
• Rash
• Lymphadenopathy
• Facial swelling
• Acute hepatotoxicity
• Hematopoietic complications
• Symptoms start after 24 days, drug should be immediately stop after 1st
sign of rash.

13. Generalised Seizure – Drug Therapy
• Tonic-clonic, myoclonic, and absence seizures:
• 1st line drug is usually Valproate
• Generalized seizures:
• Phenytoin and Carbamazepine are effective on tonic-clonic seizures but not other types of seizures
• Absence seizures:
• Valproate and Ethosuximide are equally effective in children, but only valproate protects against the
tonic-clonic seizures that sometimes develop
• Risk of hepatoxicity with valproate—should not be used in children under 2 yrs of age

14. Partial Seizure – Drug Therapy
• Without generalization
• Carbamazepine and Phenytoin are slightly more effective
• With secondary generalization
• First-line drugs are Carbamazepine and Phenytoin (equally effective)
• Valproate, phenobarbital, and primidone are also usually effective
• Adjunctive therapy for Phenytoin and carbamazepine failure: Newer drugs - Lamotrigine,
oxcarbazepine, felbamate approved for monotherapy
• Refractory partial seizures: Topiramate can be effective

15. Antiepileptic Drug: Monotherapy
• Simplifies treatment
• Reduces adverse effects
• Eighty percent of seizures can be controlled with monotherapy
• Monotherapy with different drug should be tried before 2 drugs
together
• Withdraw antiepileptic drugs slowly over several months
• Eliminate sedative drugs first (barbiturate/benzodiazepine)

16. Discontinuing AEDs
• Seizure freedom for ≥2 years
implies overall >60% chance of success
• Favorable factors
• Control achieved easily on one drug at low dose
• No previous unsuccessful attempts at withdrawal
• Normal neurologic exam and EEG
• Primary generalized seizures except JME (juvenile myoclonic epilepsy)
• Consider relative risks/benefits (e.g., driving, pregnancy)

17. Pregnancy and AEDs
• Phenytoin : Fetal hydantoin syndrome, low IQ
• Valproate : Neural tube defects
• Carbamazepine: NTD, minor malformations
• BZD: Floopy Infant Syndrome
• Other congenital malformations : Cardiac defects, Genitourinary defects, Oral clefts
• Risk with AED monotherapy 4.5%
• Risk with Polytherapy 8.6%
• Consensus : Monotherapy with lowest dose CBZ, Folate supplementation in all
• 2nd drug : Monotherapy with Valproate
(Holmes et al. N Engl J Med. 2001;344:1132–1138. [PubMed])

18. Lactation and AEDs
• Breastfeeding should be encouraged unless clear risk posed
• Probably safe:
• Carbamazepine
• Phenytoin
• Valproate
• Lamotrigine
• “Use with caution” in lactating women:
• Primidone
• Phenobarbital
• Ethosuximide
(Pennell et al. Epilepsy and Behavior. 2007. 11: 263‐9)

19. Commonly Used AEDs

20. Status Epilepticus
• Status epilepticus (SE) : a single seizure lasting more than five minutes or two or more
seizures within a five-minute period without the person returning to normal between them
• Its an medical emergency condition
• Goal of therapy:
• Rapid termination of seizure activity – more difficult to control – may lead to
permanent brain damage
• Prompt treatment with effective drugs
• Attention to hypoventilation and hypotension
• Treatment is IV only

21. Algorithm
to manage
Status
Epilepticus

22. Nursing considerations while
administering AED’s
• Phenytoin:
• Cannot be given to pregnant women.
• Black box warning: if given IV rate should not exceed 50mg per minute in
adult and 3mg/kg/min for pediatric patients. It may cause cardiac
arrhythmias and hypotension.
• Cardiac monitoring or periodic cardiac assessment
• Delirium, psychosis and confusion is the first sign of acute toxicity, serum
phenytoin level should be immediately checked.

23. Side effects:
• Purple glove syndrome
• Cardiac complications are common: hypotension & sinus bradycardia
• Pregnancy risk category D
• Dilute only with 0.9%NS not with 5D
• Contraindicated in patient with heart block
• Skin complications are rare but severe: Steven johnson syndrome
• Hepato toxic
• Bone marrow supperssion
• Gingival hyperplasia

27. Nursing considerations while
administering AED’s
• Levetiracetam:
• Taper the dose slowly.
• It may cause behavioural changes, psychosis, irritability, depression.
• Hematopoietic abnormalities
• It can also be used for pregnant women
• Review before giving it to patients with renal impaiment.

28. Nursing considerations while
administering AED’s
• Gabapentin
• Can be given to pediatric patients
• Also causes CNS depression
• Drug of choice in many neuropathic pain
• Donot give gabapentin along with antacids or within 2hours of
duration.
• Phenobarbital sodium

29. General nursing considerations:
Drug compliance
Do not stop the
drug abruptly
Set medium rate
of infusion if
needed to
administer IV
Observe and
notify early sign
of drug toxicity
and allergy
Advice to avoid
driving
Look for
refractory epilepsy
Serum phenytoin
level should be
checked
Follow up

30. •Thankyou