Pharmacology for Canadian Pharmacy

Technicians
First Canadian Edition

Chapter 12
Drugs for Seizures

Copyright © 2017 Pearson Canada Inc. 12 - 1

Learning Outcomes (1 of 2)
LO1: Compare and contrast the terms epilepsy, seizures, and
convulsions.
LO2: Recognize the possible causes of seizures.
LO3: Relate the signs and symptoms of specific types of
seizures.
LO4: Describe the pharmacological management of acute
seizures and epilepsy.
Learning Outcomes (2 of 2)
LO5: Explain the importance of patient drug compliance in
the pharmacotherapy of epilepsy and seizures.
LO6: For each of the drug classes, know representative drug
examples and explain their mechanisms of drug action,
primary actions, and important adverse effects.
LO7: Categorize the drugs used in the treatment of seizures
on the basis of their classifications and mechanisms of
action.
 Core Concept 12.1
All convulsions are seizures, but not all seizures are convulsions.
Seizure
• A disturbance of electrical activity in the brain
• Caused by abnormal neuronal discharges
Seizure and Convulsion
• Not synonymous
• Convulsions
• Involuntary, violent spasms of the large skeletal muscles of the face, neck,
arms, and legs
• Some seizures involve convulsions, others do not
 Core Concept 12.2
Many causes of seizure activity are known; a few are not.
Causes of Seizure Activity (1 of 2)
A symptom of an underlying disorder
• Infectious diseases
• meningitis, encephalitis
• Trauma
• physical or chemical trauma
• Metabolic disorders
• hypoglycemia, hyponatremia, water intoxication
Causes of Seizure Activity (2 of 2)
• Vascular diseases
• Respiratory hypoxia
• Carbon monoxide poisoning
• Cerebral vascular accidents
• Shock, Cardiac dysrhythmias
• Pediatric disorders
• Febrile seizure
• Neoplastic disease
 Core Concept 12.3
Epileptic seizures are typically identified as partial, generalized, or
special epileptic syndromes.
 Types of Seizures (1 of 3)

Partial (focal) seizures

• Limited portion of the brain
• Simple partial seizures
• Small, limited focus
• Complex partial seizures
• Involve sensory, motor, or autonomic symptoms
• Some degree of altered or impaired consciousness
• Can be proceeded by an aura
Types of Seizures (2 of 3)
Generalized seizures
• Entire brain on both sides
• Absence seizures
• Last for few seconds only, staring common sign
• Atonic seizures
• episodes are very short
• stumbling and falling for no apparent reason.
Types of Seizures (3 of 3)
Tonic-clonic seizures (grand mal seizures)
• Most common type of seizure
• Intense muscle contractions indicate the tonic phase
and apnea
• The clonic phase is characterized by alternating
contraction and relaxation of muscles
• The seizure usually lasts 1 to 2 minutes, after which
the patient becomes drowsy, disoriented, and sleeps
deeply
Special Epileptic Syndromes (1 of 3)
Febrile seizures
• Tonic-clonic motor activity lasting for 1 to 2 minutes
• Rapid return of consciousness
• Caused by rapid rise in body temperature
• 3-month to 5-year age group
Special Epileptic Syndromes (2 of 3)
Status epilepticus
• Medical emergency
• Repeated occurrence of a seizure
• Hypoxia may develop
• Hypoglycemia, acidosis, and hypothermia
• Can cause brain damage and ultimately death
Special Epileptic Syndromes (3 of 3)
Management of status epilepticus
• Treatment involves the IV administration of antiseizure medications
• During seizure activity, steps must be taken to make sure to maintain
airway
 Core Concept 12.4
Effective seizure management involves strict adherence to drug therapy.
Antiseizure Pharmacology
• Dependent on patient presentation, medical history, and associated
pathologies
• Effective therapy usually obtained with one drug
• Seizures can occur due to drug cessation, discontinuation should
occur over many weeks
Table 12.1 Suggested Drugs for the Management of Specific
Types of Seizures

Blank Blank Generalized Seizures Blank Special

Partial
Blank Seizures Absence Tonic–clonic Myoclonic
Drugs That Potentiate GABA Blank Blank Blank Blank

clobazam (Frisium) ✓ ✓ ✓ ✓

gabapentin (Neurontin) ✓ Blank Blank Blank

phenobarbital (Luminal) ✓ Blank Blank Blank

primidone (Mysoline) ✓ Blank ✓ Blank

topiramate (Topamax) ✓ ✓ ✓ ✓

Copyright © 2017 Pearson Canada Inc. 12 - 19

[Table 12.1 Continued]

Blank Blank Generalized Seizures Blank Special

Partial
Blank Seizures Absence Tonic–clonic Myoclonic
Hydantoin and Related Drugs Blank Blank Blank Blank

carbamazepine (Tegretol) ✓ Blank ✓ Blank

lamotrigine (Lamictal) ✓ ✓ ✓ ✓

levetiracetam (Keppra) ✓ ✓ ✓ ✓

oxcarbazepine (Trileptal) ✓ Blank Blank Blank

phenytoin (Dilantin) ✓ Blank ✓ Blank

valproic acid (Depakene) ✓ ✓ ✓ ✓

Succinimides Blank Blank Blank Blank

ethosuximide (Zarontin) Blank ✓ Blank Blank

Adapted from Gray, J. (2014). Therapeutic Choices. Ottawa, ON: Canadian Pharmacists Association. Copyright Canadian
Pharmacists Association, www.etherapeutics.ca.

Copyright © 2017 Pearson Canada Inc. 12 - 20

 Core Concept 12.5
Antiseizure pharmacotherapy is directed at controlling the movement of
electrolytes across neuronal membranes or affecting neurotransmitter
balance.
Goal and Action
• Suppress neuronal activity just enough to prevent abnormal or
repetitive firing
• Three general mechanisms by which antiseizure drugs work:
• Stimulating an influx of chloride ions, neurotransmitter gamma-aminobutyric
acid (GABA)
• Delaying an influx of sodium ions
• Delaying an influx of calcium ions
 Core Concept 12.6
By increasing the effects of gamma-aminobutyric acid (GABA) in the
brain, drugs reduce a wide range of seizure types.
GABA (1 of 2)
• Primary inhibitory neurotransmitter
• Suppress the firing of neurons
• Barbiturates, benzodiazepens, and some others reduce seizure
activity by augmenting the action of GABA
• GABA related drugs usually used in conjunction with other medication
GABA (2 of 2)
 Core Concept 12.7
Hydantoin and related drugs are effective in treating partial seizures and
tonic–clonic seizures.
Hydantoins
• Dampen CNS activity
• Delay the influx of sodium ions across neuronal
membranes
• Sodium channels are not blocked, just made to be less
sensitive to decrease the likelihood for an action
potential
• Drugs in this group may also affect the threshold of
neuronal firing:
• They may interfere with transduction of the excitatory
neurotransmitter glutamate.
First-Line Drugs (1 of 2)
• Dilantin (phenytoin)
• The oldest and most commonly prescribed antiseizure
medication
• First-line drugs in the treatment of status epilepticus
• Phenytoin-related drugs have a mechanism similar to
that of the hydantoins
First-Line Drugs (2 of 2)
• Examples:
• Carbamazepine (Tegretol), oxcarbazepine (Trileptal), and
valproic acid (Depakene, Depakote), and Lamotrigine
Core Concept 12.8
Succinimides are used to treat absence seizures.
Succinimides
• Affect calcium influx at neurotransmitters, hormones,
and membranes
• Calcium is fundamental in neuronal transmission
• Delay influx thereby increasing the electrical
threshold and reducing the probability of an action
potential
• Example: Zarontin (ethosuximide)
Table 12.2 Key Drugs to Treat Seizures

Classification Generic Name Original Brand Name

Barbiturate phenobarbital Phenobarb

Blank primidone Myosoline

Benzodiazepine clobazam Frisium

Gamma-aminobutyric acid (GABA) gabapentin Neurontin
derivative
Hydantoin-like carbamazepine Tegretol, Tegretol CR

Blank divalproex Epival

Blank oxcarbazepine Trileptal

Blank valproic acid Depakene

Hydantoin phenytoin Dilantin

Miscellaneous type lamotrigine Lamictal

Blank levetiracetam Keppra

Blank topiramate Topamax

Succinimide ethosuximide Zarontin

Copyright © 2017 Pearson Canada Inc. 12 - 32

Summary
• Seizures are uncontrolled neuronal brain discharges,
whose reasons are not all known
• Seizures categorized as partial, generalized, or special
epileptic syndromes
• Seizure management involves pharmacotherapy to
control the movement of electrolytes thereby
increasing the electrical threshold
• Mechanisms involve, chloride ions (GABA),
desensitization to sodium channels, and blocking of
calcium channels