NERVOUS SYSTEM 6

Drugs for Seizures • Due to hyperactivity of electrical conduction in the brain • Variety of causes (epilepsy, tumors, inflammation, trauma, others) • International Classification of Epileptic Seizure Nomenclature: • Partial (focal): simple and complex • Generalized: absence, atonic, tonic-clonic • MOA for drugs: • Potentiate GABA • Suppress Na influx across membranes

Anti-seizure Drugs – GABA
Potentiaters
Barbiturates
• Amobarbital (Amytal)
• Pentobarbital (Nembutal)
• Phenobarbital (Luminal)
• Primidone (Mysoline)
• Secobarbital (Seconal)
Benzodiazepines
• Chlorazepate (Tranxene)
• Clonazepam (Klonopin)
• Diazepam (Valium)
• Lorazepam (Ativan)
• *Status epilepticus
Miscellaneous
• Ezogabine (Potiga)
• Gabapentin (Neurontin)
• Pregabalin (Lyrica)
• Tiagabine (Gabitril)
• Topiramate (Topamax)
• Vigabatr

Anti-seizure Drugs – Na Influx Suppressants • Diminish CNS activity by delaying an influx of Na across neuronal membranes • Na channels are desensitized (not completely blocked) • Hydantoins and Phenytoin-like Drugs

Anti-seizure Drugs – continued Hydantoins: • Fosphenytoin (Cerebyx) • Phenytoin (Dilantin) • Requires loading dose • May cause toxicity r/t saturating enzymes responsible for its metabolism • Toxicity: • Sedation • Nystagmus • Ataxia • Hyperplasia • Stevens-Johnson syndrome/rashes • Peripheral neuropathy • Others Phenytoin-like Agents: • Carbamezapine (Tegretol) • Felbamate (Felbatol)* • Lamotrigine (Lamictal) • Levetiracetam (Keppra) • Rufinamide (Banzel) • Valproic acid (Depakote) • Zonisamide (Zonegran) Other: • Lacosamide (Vimpat)

Anti-seizure Drugs – Calcium Influx Suppressants • Succinimides delay entry of Ca into neurons by blocking Ca channels, increasing the electrical threshold and reducing the likelihood that an action potential will be generated • By raising the seizure threshold, succinimides keep neurons from firing too quickly, thus suppressing abnormal foci • Generally, only effective against absence seizures • Succinimides: • Ethosuximide (Zarontin) • Methsuximide (Celontin)

Anti-seizure Drug Therapy
1. Start with one drug
2. Increase dose until clinical effect or toxicity
3. Add a second drug, as needed
• Combination therapy
4. If able to discontinue, always taper

Neuromuscular Disorders • Damage to the motor area of the cerebral cortex that controls movement  Stroke, spinal injury/trauma, neurodegenerative diseases, dystonia • Muscle Spasms: involuntary contraction of the muscle or muscle groups • Spasticity: continuous state of contraction of certain muscle groups • Pharmacologic therapy:  Skeletal muscle relaxants, antispasmodics  Neuromuscular blocking agents

Skeletal Muscle Relaxants Indications: Muscle spasm, spasticity Agents: Baclofen (Lioresal), carisoprodol (Soma), methocarbamol (Robaxin), tizanidine (Zanaflex) MOA: Not fully understood; inhibits motor neurons within the CNS/spinal cord Adverse Effects: Drowsiness, dizziness, dry mouth, sedation, ataxia, lightheadedness, urinary retention, hypotension, bradycardia Comments: Use lower initial dose in geriatrics Reduce dose for liver or renal impairment

Direct-acting Antispasmodics
Indications: Muscle spasm, spasticity
Agents: OnabotulinumtoxinA (Botox, Dysport)
dantrolene (Dantrium)
MOA: OnabotulinumtoxinA: blocks the release of acetylcholine from
cholinergic nerve terminals
dantrolene: interferes with the release of calcium in skeletal
muscle
Adverse
Effects:
OnabotulinumtoxinA: anaphylaxis, headache, dysphagia,
ptosis, local muscle weakness, pain, muscle tenderness
dantrolene: muscle weakness, dizziness, hepatic necrosis
Comments: OnabotulinumtoxinA max dose: do not exceed 360 units in a
3-month interval;
Botulinum toxin products are not interchangeable
Dantrolene max dose: 100 mg 4 times a day; monitor LFT’s