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Human disease and therapeutics 2020 > Dr. Smith Epilepsy and Anti seizure drugs > Flashcards

Dr. Smith Epilepsy and Anti seizure drugs Flashcards

1
Q

What is a finite clinical manifestation of abnormal and excessive excitation of a population of cortical neurons known as?

A

-Seizure

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2
Q

What is a syndrome characterized by 2 or more recurrent seizures that are unprovoked by a systemic or neurologic insults known as?

A

-Epilepsy

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3
Q

What is a sequence of events that convert normal neuronal networks into a hyperexcitable networks known as?

A

-Epileptogenesis

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4
Q

What is a continuous seizure lasting more than 30 min or 2 or more seizures without full recovery of consciousness between them known as?

A

-Status Epilepticus

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5
Q

How many people will be diagnosed with epilepsy throughout a lifetime?

A

1 in 26

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6
Q

What characterizes epilepsy?

A

-2 or more (recurrent) seizures that are unprovoked

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7
Q

Any seizure lasting more than 5 minutes is treated clinically as what?

A

-Status Epilepticus

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8
Q

What is the most common causes of epilepsy in pediatric patients?

A
  • Genetic susceptibility
  • Perinatal and neonatal insults
  • CNS infection/fever
  • Trauma
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9
Q

What are the most common causes of epilepsy in adults?

A
  • Trauma
  • Neonatal DEFS
  • CNS infection/fever
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10
Q

What are the most common causes of epilepsy in the elderly?

A
  • Neoplasms
  • Stroke
  • Neurodegenerative disorders
  • Trauma
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11
Q

What are common seizure precipitants?

A
  • Metabolic and or electrolyte imbalance
  • Stimulant intoxication
  • Depressant withdrawal
  • Sleep deprivation
  • Reduction or inadequate ASD treatment
  • Hormonal variations
  • Stress
  • Hypoxia
  • High fever or CNS infection
  • Concussion and or closed head injury
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12
Q

What are the two subsets of etiologies of epilepsy?

A
  • Inherited

- Acquired

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13
Q

What are the three types of partial seizures?

A
  • Simple partial
  • Complex partial
  • Secondarily generalized
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14
Q

What type of partial seizure is a single focus and the pt is fully aware and responsive?

A

-Simple partial

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15
Q

What type of partial seizure has a focal onset with local spread and the pt is initially aware and responsive but may develop some memory impairment if limbic system is involved?

A

-Complex

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16
Q

What are some common stimulant seizure precipitants?

A
  • Cocaine
  • Ephedrine
  • Caffeine
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17
Q

What type of partial seizure is when the pt is initially aware and responsive but them loss of responsiveness and any memory as seizure then fully generalizes to involve the entire cortex, midbrain and thalamus?

A

-Secondarily generalized

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18
Q

What is the loss of awareness and lack of responsiveness, generalization from onset known as?

A

-Generalized Seizures

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19
Q

What are different types of generalized Seizures?

A
  • Tonic-clonic (can be tonic or clonic as well)
  • Absence
  • Atonic
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20
Q

What does tonic mean?

A

-Stiffening

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21
Q

What does clonic mean?

A

-Jerking spasms

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22
Q

What is the phenotype of a simple partial seizure?

A

-Depends on areas of focal cortical involvement

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23
Q

How are the Foci of simple partial seizures confirmed?

A

-EEG

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24
Q

If the motor cortex is involved in a simple partial seizure what does it look like?

A
  • Facial grimace

- Chewing

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25
Q

If the somatosensory cortex is involved in a simple partial seizure what does it look like?

A
  • Numbness

- Tingling

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26
Q

If the occipital cortex is involved in a simple partial seizure what does that produce?

A
  • Visual disturbances
  • Blurred vision
  • Hallucinations
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27
Q

How long do simple partial seizures typically last?

A

-Less than 90 seconds

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28
Q

What is a pt like during a simple partial seizure?

A

-Normal awareness, memory and consciousness throughout the seizure

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29
Q

How does a complex partial seizure spread?

A

-Locally or Bilaterally

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30
Q

What might become impaired during a complex partial seizure?

A
  • Awareness
  • Memory
  • Consciousness
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31
Q

What is the duration of a complex partial seizure?

A

-Less than 120 seconds

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32
Q

If a complex partial seizure fully generalizes what is it known as?

A

-Secondarily generalized seizure

33
Q

How can secondarily generalized seizures begin?

A

-Simple or complex partial seizures

34
Q

How long does a secondarily generalized seizure last?

A

-Less than 240 seconds

35
Q

What is the Postictal phase?

A

-Confusion, Somnolence, with or without transient focal deficit can last for minutes up to hours

36
Q

Absence seizures probably represent abnormal interactions between what?

A

-Cortical and thalamic transmissions

37
Q

What does a typical absence seizure look like?

A

-Impaired awareness and responsiveness for about 2 - 15 seconds

38
Q

What are the three mechanisms of action for most commonly used ASDs?

A
  • Enhancement of GABA mediated inhibition
  • Reduction of excitatory transmission (glutamate)
  • Modification of ionic conductance (Na, Ca 2+, K)
39
Q

What is the purpose of the modification of ionic conductance

A

-Targeted at slowing neurotransmission in hopes of slowing or preventing seizure spread

40
Q

How is the therapeutic index calculated?

A

-Median toxic dose/ median effective dose at any given time

41
Q

What does the modulation of voltage dependent Na + or Ca 2+ channels lead to?

A

-Secondary inhibition of neurotransmitter release (particularly glutamate)

42
Q

If you take a CYP450 inhibitor what can happen with the therapeutic index?

A

-You can start heading towards the toxic dose

43
Q

When would you use Carbameaepine (tegretol)?

A
  • Partial simple or complex seizures

- Generalized tonic-clonic seizures

44
Q

Carbamazepine is a great drug for partial epilepsy but potential for what is high?

A

-Drug drug interaction

45
Q

What is the Mechanism of action of Carbamazepine (Tegretol)?

A

-Blocks voltage-gated Na+ channels to inhibit repetitive firing in neurons

46
Q

What is a rare side effect from carbamazepine?

A

-Stevens Johnson syndrome?

47
Q

-What drug should you avoid in absence seizures?

A

-Carbamazepine

48
Q

If you give Carbamazepine to someone with absence seizures what might happen?

A

-May aggravate spike wave seizures

49
Q

What are the symptoms of Stevens johnson syndrome?

A
  • Fever
  • Sore throat
  • Fatigue
  • Painful lesions in the mucous membranes in the mouth and lips
  • Spreads rapidly to face, trunk, arms, legs and feet
50
Q

What pts are most at risk for getting stevens johnson syndrome?

A

-Pts on sodium channel blocker ASDs

51
Q

What can raise Carbamazepine levels in plasma?

A

-Grapefruit juice by inhibiting its breakdown by CYP3A4

52
Q

What does Carbamazepine do to CYP3A4 enzyme?

A

-Inhibits it leading to a decrease in Carbamazepine metabolism leading to increases in plasma levels of the drug

53
Q

When do you use Ethosuximide (Zarontin)?

A

-Uncomplicated absence only

54
Q

What drug do you use for uncomplicated absence only ?

A

-Ethosuximide (Zarontin)

55
Q

What side effects does Ethosuximide have?

A
  • May worsen partial and tonic clonic seizures

- Minor weight loss

56
Q

T/F Ethosuximide has a short half life

A
  • False

- Long half life

57
Q

What is the mode of action of ethosuximide?

A

-Reduces T-type Ca2+ channel currents in thalamic pacemaker neurons

58
Q

What is Phenytoin (Dilantin) used for?

A
  • Partial simple and complex

- Generalized tonic clonic

59
Q

What is a dentally related side effect of Phenytoin (Dilantin)?

A

-Gingival hyperplasia

60
Q

What type of kinetics does Phenytoin have at high doses?

A

-Zero-order

61
Q

What is Phenytoin contraindicated for?

A

-Absence seizures

62
Q

What is the mode of action of phenytoin?

A

-Blockade of Na+ channel during repetitive firing

63
Q

What must you do if a drug has zero order kinetics?

A

-Monitor plasma levels often and titrate dose as needed

64
Q

What do you use Topiramate (Topamax) used for?

A
  • Partial simple complex
  • Generalized tonic-clonic
  • Lenox-Gastaut syndrome
65
Q

What are side effects of topiramate (topamax)?

A
  • Word recall problems
  • weight loss
  • open angle glaucoma (not very common though)
  • Renal calculi
66
Q

What can topiramate (topamax) do to estrogen?

A

-Increase metabolism making oral contraceptives less effective (must use secondary means of birth control to avoid pregnancy)

67
Q

Topiramate has multiple Modes of action and is broad spectrum, what are the MOA?

A
  • blocks repetitive firing of voltage gated Na+
  • Inhibits Ca2+ currents
  • Inhibits AMPA/kainate receptors
  • Potentiates GABA currents
68
Q

What is Valproic Acid (Depakote) used for?

A 
-Generalized absence
Generalized atypical absence
-Myoclonic
-Tonic clonic
-Partial simple and complex
69
Q

What are common side effects of valproic acid (Depakote)?

A
  • Weight gain

- Reye-like syndrome: hepatic failure

70
Q

What is Valproic acid contraindicated in?

A

-pts with hepatic disease or significant hepatic dysfunction

71
Q

What are increased risks of Valproic Acid?

A
  • Teratogenicity

- Spinal bifida

72
Q

What is the pregnancy risk for Valproic acid?

A

-Category D risk

73
Q

What are three ASD drugs used for partial seizures?

A
  • Carbamazepine
  • Phenytoin
  • Topiramate (if secondarily generalized)
74
Q

What ASD drugs are used for generalized onset tonic clonic seizures?

A
  • Valproate

- Topiramate

75
Q

What ASD drugs are used for absence seizures?

A
  • Ethosuximide (uncomplicated)

- Valproate (complicated)

76
Q

What ASD drugs are used for Status epilepticus?

A
  • Diazepam

- Phenytoin

77
Q

What are the principles of ASD treatment?

A
  • Match proper drug to seizure type
  • Try monotherapy first
  • monitor plasma levels of drugs
  • Tailor therapy to individual patient
78
Q

What are characteristics of ASDs?

A
  • Good absorption
  • Hepatic metabolism
  • Side effects are common
  • Drug interaction are common

Human disease and therapeutics 2020 (60 decks)

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