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Pharmacology > Epilepsy > Flashcards

Flashcards in Epilepsy Deck (46)
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1
Q

What is epilepsy?

A

a chronic disease characterized for recurrent seizures

2
Q

What is a seizure?

A

A short term episode of abnormal firing of the cerebral neurons
- seizures are classified as partial or generalized

3
Q

What are some common causes of seizures?

A

fever, head injury, heredity, alcohol withdrawal, metabolic disorder

4
Q

What is a partial (focal) seizure?

A

initiated by neurons in a localized area of one cerebral hemisphere

  • Simple: no loss of consciousness
  • complex: impaired consciousness often with automatisms
  • secondary generalizedL seizures spread to activate both hemispheres
5
Q

What is a generalized seizure?

A

simultaneous activation of both cerebral hemispheres

  • Tonic clonic: loss of consciousness, extension then jerking of the body
  • Absence seizure: impaired consciousness sometimes with automatisms
  • Other types can exist as well
6
Q

What is the motor homunculus?

A
  • a representation of anatomical structures in the brain
  • the larger the representation of the body part on the motor homunculus, the more the brain will stimulate that one area of the body
  • this can help to give an idea as to the brain location of the seizure focus when we see one part of the body more activated than another
7
Q

Partial Seizure

A

initiated by neurons in a localized area of one cerebral hemisphere

8
Q

What do electroencephalograph readings tell us about seizures?

A
  • show abnormal electrical activity in specific brain regions during a partial seizure-this is compared to an EEG of a normal brain
9
Q

Complex partial seizure

A

initiated in neurons in a localized area of one of the cerebral hemispheres, but spreads very easily
- seizures spread and EEG similar to simple partial seizure

10
Q

Partial Seizure with Secondary Generalization

A
  • initiated in neurons in a localized area of one cerebral hemisphere, then seizures spread to activate both hemispheres
11
Q

Generalized tonic-clonic seizure

A

simultaneous activation of both the cerebral hemispheres

- point of origin is in the thalamus - many of these seizures have a genetic origin

12
Q

What is considered status epilepticus?

A

When a seizure lasts for longer than 5-10 minutes

- this is considered a medical emergency

13
Q

What does an EEG show during a generalized tonic-clonic seizure?

A
  • abnormal electrical activity in all brain regions during a generalized tonic-clonic seizure
14
Q

What is an absence seizure?

A

no motor involvement in the upper and lower body- only a twitching of the eyes sometimes
- often goes undiagnosed and is mistaken for the child “packing out”

15
Q

What does an EEG show in an absence seizure?

A

shows abnormal slow wave electrical activity in all brain regions

16
Q

What are the different MOAs for seizure medications?

A
  1. use dependent blockade of voltage-dependent Na channels
    - reduces the rate of Na channel opening
  2. inhibit excitatory (glutamate) neurotransmission
    - decrease glutamate exposure and reduce neuronal firing
  3. increase inhibitory (GABA) neurotransmission
    - enhance chloride influx, hyperpolarize neurons and reduce neuronal firing
  4. block voltage activated calcium channels
    - neurons in thalamus are dependent on calcium channel pacemaker for depolarization
    - depolarization of thalamic neurons activates cortical neurons
17
Q

Using a dependent block of sodium channels decreases what?

A

neuronal firing rate

18
Q

Decreasing ____ and increasing ____ can lead to a decrease in seizure activity?

A
  1. glutamate

2. GABA

19
Q

Neurons in the thalamus are dependant on what for depolarization?

A
  • calcium channel pacemakers

- blocking these channels slows the pacemaker

20
Q

What drugs can be used to treat a partial (focal) seizure?

A
  • carbamazepine, phenytoin or valproate
21
Q

What drugs can be used to treat a tonic-clonic seizure?

A

carb., phenytoin pr valproate

22
Q

What drug can be used to treat a generalized absence seizure?

A

ethosuximide

23
Q

What drugs can be used to treat a generalized tonic-clonic or absence seizure?

A

valproate

24
Q

What drugs can be used to treat an atypical generalized seizure?

A

valproate

25
Q

How does carbamazepine work?

A
  • inhibits voltage gates sodium channels
  • similar to TCAs
  • induces its own metabolism
  • initial half life of 36 hours- goes down to 8-12 hours
  • can enhance metabolism of many other anti epileptics including phenytoin and valproate toxicity
26
Q

What are the adverse effects and toxicities of carbamazepine?

A

double vision, ataxia, nausea, drowsiness

- skin rash is common, leukopenia (lower than normal number of white blood cells)

27
Q

How does phenytoin work?

A
  • blocks voltage gated Na channels
  • absorption differs among formulations
  • dose dependent (saturation) metabolism- half life ranges from 12-36 hours
  • highly bound to plasma proteins (decreases bioavailability)
  • induces CYP3A4, increases metabolism of many drugs
  • induces metabolism of carbamazepine, valproate, vitamin K and contraceptives(decreases effectiveness of contraceptives)
  • metabolism is enhances by phenobarbital and carbamazepine, requires dose adjustment
28
Q

What are the adverse effects of phenytoin?

A
  • double vision and ataxia - balance problems, uncoordinated movements
  • requires a dose adjustment
  • gingival hyperplasia (gun inflammation). hirsutism (hair growth)
  • mild peripheral neuropathy
  • megaloblastic anemia - dysfunctional RBCs, can occur due to altered folate metabolism
  • osteomalacia- decreased calcification of bone. Can occur due to altered vitamin D metabolism
29
Q

How does phenobarbital work in epilepsy?

A
  • enhances the inhibitory effects of GABA
  • primidone is metabolized to phenobarbital
  • metabolism is first order, half like is around 4 days
  • drug interactions are common with vitamin K and oral contraceptives
  • induces its own metabolism
30
Q

What are the adverse effects associated with phenobarb?

A
  • drowsiness, eye movements, ataxia, respiratory depression, decreased motor skills
  • skin rash due to hypersensitivity
  • psychological and physiological dependence
31
Q

How does Gabapentin work?

A

increases release of GABA from neurons

  • appears to decrease GABA metabolism
  • does not induce of inhibit hepatic enzymes
  • minimal binding to plasma proteins
32
Q

What are the adverse effects of Gabapentin?

A

-sedation, dizziness, headache, temor and ataxia - GI effects (nausea and constipation)

33
Q

How does topiramate work?

A
  • inhibits voltage sensitive Na channels, increases GABA effects and inhibits glutamate receptors
  • approved for adjunctive therapy
  • metabolism is affected by other drugs
34
Q

What are the adverse effects and toxicity of topiramate?

A
  • fatigue, dizziness, mental slowing and nausea
35
Q

Lamotrigine

A
  • blocks voltage gated sodium channels

- used for adjective therapy

36
Q

Adverse effects of lamotrigine

A
  • dizziness, headache, skin rashes
37
Q

How does ethosuximide work?

A

blocks voltage activated calcium channels

38
Q

How does clonazepam work?

A
  • enhances the inhibitory effects of GABA
39
Q

Valproate

A
  • voltage gated Na and Ca channels - enhances inhibitory effects of GABA
  • binds plasma proteins
  • inhibits metabolism os other drugs
40
Q

What are the adverse effects associated with valproate?

A
  • tremor in higher concentrations

- risk of spina bifida

41
Q

What is given for status epileptics?

A
  • IV diazepam or IV lorazepam are used to stop seizure
  • phenytoin may then be initiated for longer term control
  • anti-epileptics are gradually increased
42
Q

Pregnancy requires tx considerations- what are they?

A
  • always a challenge since AEDs can harm the fetus but so can uncontrolled seizures
  • risk to fetus from uncontrolled seizures is greater
  • lowest effect dose should be used
  • only one drug at a time
  • increase in dose is necessary during the course of the pregnancy
43
Q

Which anti-epileptics enhance the metabolism of oral contraceptives?

A

-phenytoin and phenobarbital

44
Q

Which drugs can cause osteomalacia?

A

phenytoin, phenobarbital

45
Q

Which drugs enhance metabolism of other anti-epileptics?

A
  • phenytoin, carbamazepine, phenobarbital
46
Q

Which drug inhibits metabolism of other anti-epileptics?

A
  • valproate