Lecture 5 (Quiz 1)

Question 1

What is a finite clinical manifestation of abnormal &

excessive excitation of a population of cortical neurons?

Answer 1

• Seizure

Question 2

What is a syndrome characterized by chronic, recurrent seizures unprovoked by systemic or neurologic insults?

Answer 2

• Epilepsy

Question 3

What is a sequence of events that converts a normal

neuronal network into a hyper hyperexcitable network?

Answer 3

• Epileptogenesis

Question 4

Seizures occur in ___% of the population. Epilepsy occurs in ___% of the population.

Answer 4

• Seizures: 10%

- Epilepsy: 1% (1 out of 26)

Question 5

What is the Etiology of epilepsy? What two things are the cause of this? What are some Precipitants of Seizures?

Answer 5

• Is caused by mutations in Ion Channels which creates an unbalance in the excitation and inhibition of the body.
• They can be Acquired (from infection, trauma, and other pathologies). Or they can be Inherited (due to rare genes).
• • Metabolic and/or Electrolyte Imbalance • Stimulant intoxication • Sedative or ethanol (i.e., depressant) withdrawal • Sleep deprivation • Reduction or inadequate ASD treatment • Hormonal variations • Stress • Hypoxia • Fever or systemic infection • Concussion and/or closed head injury.

Question 6

There are two categories of seizure classification, what are they? What are they types of seizures found within each category (both have 3)?

Answer 6

• Partial Seizures and Generalized Seizures.
• Partial Seizures:
  Simple Partial
  Complex Partial
  Secondarily generalized
• Generalized Seizures:
  Tonic-clonic (“grand mal”)
  Absence (“petit mal”)
  Atonic (“drop”)

Question 7

What type of seizure has a localized focus, normal awareness, memory, and consciousness
throughout seizure, and has the shortest duration (60-90 seconds)? This has two types of sublclassification depending on cortical involvement, what are they?

Answer 7

• Simple Partial Seizures
  Subclassifications:
  
  • Motor symptoms (i.e., facial grimace, chewing, etc).
  • Somatosensory symptoms (i.e., numbness, tingling).

Question 8

What type of seizure has localized onset. Spreads, often bilaterally, usually limbic involvement. Awareness, memory, and/or consciousness may be impaired as seizure progresses. Clinical manifestations vary with site of origin and degree of spread. Does not fully generalize. And has a duration of 15 sec. – 120 sec.?

Answer 8

• Complex Partial Seizures

Question 9

What type of seizure begins as simple and/or complex partial seizures. They fully generalize with variable symmetry, intensity, and duration of tonic (stiffening) and clonic (jerking) phases. Usual duration of 30-240 sec. And have a Postictal Phase that contains confusion, somnolence, with or without transient focal deficit can lasts minutes-hours?

Answer 9

• Secondarily Generalized Seizures

Question 10

What type of seizures involve the loss of awareness, a lack of responsiveness, and are generalized from onset? What is another term for stiffening? What is another word for “jerking” spasms?

Answer 10

• Tonic-clonic (“grand mal”), Absence (“petit mal”) and Atonic (“drop”). (AKA: Generalized seizures).
• Stiffening: Tonic
• “Jerking” Spasms: Clonic

Question 11

What are some things that make up the properties of an Ideal Antiseizure Drug (ASD)? 4 things

Answer 11

• Wide Therapeutic Index
• Long half-life (t1/2)
• Water soluble (easily absorbed)
• NO: organ toxicity, teratogenicity, drug-drug interactions, protein binding, active metabolites.

Question 12

Approximately ___ of all Antiseizure Drugs are Refractory (ineffective) to all epilepsy patients.

Answer 12

• 1/3 (~33%)

Question 13

What are the 3 main mechanisms for Antiseizure drugs?

Answer 13

• Enhancement of GABA-mediated inhibition (Increase GABA)
• Reduction of excitatory transmission (i.e., glutamate)
• Modification of ionic conductance (i.e., Na+, Ca2+, K+ by slowing neurotransmission, in hopes of slowing or
  preventing seizure spread.)

Question 14

What drug’s mechanism of action is done by blocking use-dependent voltage-gated Na+ channels to inhibit repetitive firing in neurons? What types of seizures is this good for? What are the negatives of using this drug (4)?

Answer 14

• Carbamazepine
• Partial Simple/Complex, and Generalized Tonic-Clonic
• High drug to drug interaction, should avoid in cases of ABSENCE seizures (aggravation of spike-wave seizures), it may cause Stevens-Johnson syndrome (painful lesions in the mucous membranes in the mouth
  and lips, spreads rapidly to face, trunk, arms, legs, & feet), and Grapefruit Juice should be avoided due to its ability to increase plasma levels of Carbamazepine.

Question 15

What drug’s mechanism of action is done by reducing T-type Ca2+ channel currents? What types of seizures is this good for? What are the negatives of this drug (2)?

Answer 15

• Ethosuximide
• Uncomplicated Absence Seizures only **(Has a very long half-life (t1/2: 40 Hours) making it easy to use).
• Minor weight loss and has a very narrow clinical spectrum.

Question 16

What drug’s mechanism of action is done by use of a dependent blockade of Na+ channel during repetitive firing? What types of seizures is this good for? What are the negatives of this drug (4)?

Answer 16

• Phenytoin
• Partial Simple/Complex, and Generalized Tonic-Clonic
• Causes gingival hyperplasia, has Zero-order kinetics at high doses (check plasma levels often, titrate dose as needed check plasma), birth defects, and should avoid in cases of ABSENCE seizures (aggravation of spike-wave seizures).

Question 17

What drug’s mechanism of action is Broad and done by blocking repetitive firing of voltage gated Na+ channels, inhibits Ca2+ currents, inhibits AMPA/kainate receptors, & potentiates GABA currents? What types of seizures is this good for? What are the negatives of this drug (3)?

Answer 17

• Topiramate
• Partial Simple/Complex, and Generalized Tonic-Clonic and Lennox-Gastaut Syndrome.
• Word recall problems, weight loss, increased metabolism of estrogen (must use secondary means of birth control to avoid pregnancy).

Question 18

What drug’s mechanism of action is Broad and done by blocking VGSCs (main mechanism), reduces NMDA currents, increases GABA-mediated Cl- currents? What types of seizures is this good for? What are the negatives of this drug (5)?

Answer 18

• Valproic Acid (Valproate)
• Partial Simple/Complex, and Generalized Absence, Atypical absence, Myoclonic epilepsy and Tonic-clonic seizures.
• Weight gain, can cause Reye-like syndrome, can cause Hepatic failure, and has an increased risk of teratogenicity & neural tube defects (like Spina Bifida and other birth defects, avoid if pregnant).

Question 19

In summary which drugs should be used for Partial Seizures? Generalized Onset Tonic-Clonic Seizures:

Answer 19

• Partial Seizures:
  • Carbamazepine, • Phenytoin, • Topiramate (If secondarily
  generalized).
• Generalized Onset-Tonic Clonic Seizures:
  • Valproate, • Topiramate
• Absence Seizures:
  • Ethosuximide (uncomplicated) • Valproate (complicated)