Pharmacological treatment of seizures part 2

Question 1

Lacosamide

1. MOA:
2. Use:
3. Waldo:
4. Indication:
5. AE:

Answer 1

Lacosamide

1. MOA: enhanced slow inactivation of the Na+ channel, blocks the actions of neurotrophic factors on axonal and dendritic growth
2. Use: approved for adjunctive therapy in pt. 16+ yo
3. Waldo: has no effect on CYP450s so drug interactions are rare
4. Indication: partial seizures
5. AE: dizziness, headache, nausea, diplopia

Question 2

Levetircetam:

1. MOA:
2. Indications:
3. AE:

Answer 2

Levetircetam:

1. MOA: binds selectively to synaptic vesicle protein SV2A
   
   1. ​protein my modify the synaptic release of glutamate and GABA
2. Indications: partial, primary generalized tonic-clonic, myoclonic seizures in juvenile myoclonic epilepsy
3. AE: somnolence, asthenia, dizziness, and CNS depression

Question 3

Topiramate

1. MOA:
2. AE:

Answer 3

Topiramate

1. MOA: Blocks repetitive neuronal firing through blockade of Na+ channels, potentiates GABA’s effects, weak carbonic anhydrase inhibitor
2. AE: usually occur when establishing the dose
   
   1. somnolence, fatigue, dizziness, cognitive slowing, paresthesias, nervousness and confusion
   2. myopia nad glaucoma
   3. metabolic acidosis
   4. urolithiasis

Question 4

Zonisamide

1. MOA:
2. Uses:
3. AE:

Answer 4

Zonisamide

1. MOA: inhibition of Ca+ and Na+ channels
2. Uses: partial, generalized tonic-clonic, infantile spasms
3. AE: drowsiness, cognitive impairment and serious skin rashes, metabolic acidosis

Question 5

Ezogabine

1. MOA:
2. Indications
3. AE

Answer 5

Ezogabine

1. MOA: opens KCNQ2/3 voltage gated POTASSIUM channels, activating the M-current, which regulates neuronal excitability and suppresses epileptic activity
2. Indications: adjunct in partial seizures
3. AE: dizziness, somnolence, urinary retention

Question 6

Ethosuximide

1. MOA:
2. Indications:
3. AE:

Answer 6

Ethosuximide

1. MOA: Inhibits the Ca++ currents of T-Type currents
   
   1. T-type Ca++ channels provide pacemaker currents in thalamus neurons, they generate the rhymic cortical discharge of an absense attack
2. Indications: Absence
3. AE:
   
   1. GI: pain/N/V
   2. transient lethargy or fatigue
   3. blood dyscrasias,
   4. SLE

Question 7

Valproic Acid and Sodium Valproate:

1. MOA:

Answer 7

Valproic Acid and Sodium Valproate:

1. MOA:
   
   1. blocks high frequency neuronal firing
      
      1. blockade of Na+ currents
      2. blockade of NMDA receptor mediated excitation
      3. GABA levels are increased (enhanced synthesis or inhibited clearance)

Question 8

Valproic Acid and Sodium Valproate

1. Clinical Uses:

Answer 8

Valproic Acid and Sodium Valproate

1. Clinical Uses:
   
   1. absence seizures in the presence of generalized tonic-clonic attacks
   2. myoclonic seizures
   3. simple partial
   4. complex partial
   5. partial with secondarily generalized tonic-clonic
   6. tonic-clonic
   7. bipolar disorder
   8. migraine prophylaxix

Question 9

Valproic Acid and Sodium Valproate

1. Drug interactions:
2. Toxicity:
   
   1. Adverse effects
   2. Black Box

Answer 9

Valproic Acid and Sodium Valproate

1. Drug interactions: displaces phenytoin from plasma proteins (higher levels of phenytoin in blood), inhibits metabolism of phenobarbital, phenytoin, carbamazepine, decreases clearance of lamotrigine
2. Toxicity:
   
   1. Adverse effects: N/V, fine tremor at high [drug], thrombocytopenia
   2. Black Box: hepatotoxicity in young patients (<2) or pts taking multiple drugs, treat with L-carnitine, pancreatitis, increased risk of spina bifida if taken during pregnancy

Question 10

Additional Therapies for Seizures

1. what are they (3)

Answer 10

There are three additional therapies that can be used in a seizure

1. diazepam
2. Lorazepam
3. Acetazolamide

Question 11

Benzodiazepines (-pams and -lams)

1. MOA
2. Use:

Answer 11

Benzodiazepines (-pams and -lams)

1. MOA: increase GABA inhibition but do not work as GABA
   
   1. they bind to allosteric site on GABA_A receptor
2. Use:
   
   1. Diazepam: can be given IV or rectally or orally for long term treatment. stops continuous seizure activity
   2. Lorazepam: treats continuous seizure activity

Question 12

Acetazolamide

1. MOA:
2. Indication:

Answer 12

Acetazolamide

1. MOA: Inhibits carvonic anhydrase
2. Indication: all seizure types but tolerance develops quickly

Question 13

What are special considerations in a patient with

Status Epilepticus?

Answer 13

Status Epilepticus is defined as recurrent episodes of tonic-clonic seizures.

The patient is unconscious and without normal muscle movement between episodes leading to a lack of oxygen that can cause brain damage

immediate cardiovascular, respiratory, and metabolic management

Question 14

Status Epilepticus

1. First Line:
2. 2nd Line:
   
   1. if no response:

Answer 14

Status Epilepticus

1. First Line: IV Diazepam or lorazepam (30-45 min. seizure free)
2. 2nd Line: Phenytoin
   
   1. monitor cardiac rhythm and BP in elderly
   2. IV Fosphenytoin (safer and more potent than phenytoin)
      
      1. if no response: phenobarbital if no response to phenytoin, but watch out for respiratory depression

Question 15

Women of child-bearing age who suffer from seizures:

1. when do seizures happen most frequently?
2. What drugs require non-hormonal methods of birth control?

Answer 15

seizures occur with an increased frequency at the time of menses.

non-hormonal methods of birth control should be used with

phenytoin, phenobarbital, carbamazepine, topiramate, oxcarbazepine, felbamate

PPCTOF

Question 16

teratogenicity

1. Phenytoin
2. phenobarbital and carbamazipine
3. valproate:
4. topiramate:

Answer 16

teratogenicity

1. Phenytoin: fetal hydantoin syndrome
2. phenobarbital and carbamazipine: cleft lip and palate, microcephaly, brain malformations
3. valproate: spina bifida
4. topiramate: hypospadias

Question 17

when can we take a patient off of seizure medication?

Answer 17

the patient must be seizure- free for several years but the withdrawl may cause an increase in frequency and severity of seizures.

Benzos and Barbiturates are difficulte to discontinue