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Flashcards in Exam 2 Deck (39)
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1
Q

Seizures

A

manifestation of an abnormal and excessive excitation and synchronization of cortical neurons

2
Q

Epilepsy

A

chronic dx characterized by spontaneous recurrent seizures

3
Q

Convulsions

A

involuntary, paroxysmal skeletal muscle contractions

4
Q

Partial Seizures

A
  1. Simple= limited motor or sensory signs, consciousness intact
  2. Complex= consciousness impaired
  3. Secondary Generalized= symptoms increase until it resembles a generalized seizure
5
Q

Generalized Seizures

A
  1. Absence (petit mal)= sudden, brief loss of consciousness
  2. Myoclonic sz= sudden brief “shocklike” contractions of muscles
  3. Clonic sz= rhythmic, synchronized contractions throughout the body, loss of consciousness
  4. Tonic sz= generalized, sustained ms contraction throughout the body, loss of consciousness
  5. Tonic-Clonic sz(grand mal)= major convulsions of entire body, loss of consciousness
  6. Atonic sz= sudden loss of ms tone in the head and neck; consciousness may be maintained or lost briefly
6
Q

Status Epilepticus

A
  • more than 30 minutes of continuous seizure activity
  • 2 or more sequential seizures spanning this period w/o full recovery b/t seizures (on-going sz)
  • medical emergency
  • tx w/ short-acting benzos (diazepam & lorazepam)
  • use rectal benzo gel for kids
7
Q

Rationale for Anti-Epileptic drugs

A
  • ↓ the frequency/ severity of sz in epilepsy pts
  • treats sxs of sz not the underlying epileptic condition
  • goal= maximize QOL by minimizing sz and ADLs
  • effective in 60% of pts w/ epilepsy (sz free) 20% experience big sz reduction
8
Q

PK & PD of Anti-Epileptic drugs test

A
  • good oral absorption & bioavailability
  • most metabolized in liver, but excretion is UNCHANGED in kidneys
  • classic AEDs generally have more severe CNS sedation than newer drugs
  • because of overlapping mechanisms of action; best drug can be chosen based on minimizing side effects in addition to efficiency
9
Q

Classical Anti-Epileptic Drugs

A
  • phenytoin
  • phenobarbital
  • carbamazepime
  • primidone
  • ethosuximide
  • valoproate (valproic acid)
10
Q

Newer Anti-Epileptic Drugs

A
  • lamotrigine
  • felbamate
  • topiramate
  • gabapentin/pregabalin
  • tiagabine
  • vigabatrin
  • oxycarbazepine
  • levetiracetam
  • fosphenytoin
11
Q

Side Effects of Anti-Epileptic Drugs

A
  • sedation: especially w/ barbiturates
  • cosmetic: phenytoin (hairy tongue, severe dermatologic effect)
  • weight gain- valproic acid & gabapentin
  • weight loss- topiramate
  • reproductive fxn- valproic acid
  • cognitive- topiramate
  • behavioral- felbamate, leviteracetam
  • allergic- many
12
Q

Causes of Hyperexcitability in Epilepsy

A
  • excitatory post synaptic potentials (EPSPs)
  • inhibitory post synaptic potentials (IPSP)
  • changes in voltage gated ions channels
  • alteration of local ion concentrations
13
Q

Major NTs in the brain (Epilepsy)

A
  • glutamate
  • GABA
  • ACh
  • DA
  • serotonin
  • histamine
14
Q

Cellular Mechanism of Sz Generation

A
  • Excitation (too much):
    - ionic: inward Na⁺ & Ca⁺⁺ currents
    - NT= glutamate, aspartate
  • Inhibition (too little)
    - ionic: inward Cl⁻, outward K⁺ currents
    - NT= GABA
15
Q

Target for Anti-Epileptic Drugs

A
  • ↑ inhibitory nt system such as GABA
  • ↓ excitatory nt system- glutamate
  • block voltage-gated inward (+) currents- Na⁺ & Ca⁺⁺
  • ↑ outward (+) current- K⁺
  • many AEDs have multiple MOAs
16
Q

Dicarbamates- Felbamate (felbatol)

A

Indicated for tx of:

  • partial sz in adults and children
  • generalized absence szs (Lennox-Gastaut syndrome) in children

Potent AED, lacks sedative effect (unlike other AED)

MOA:

  • antagonizes the glycine site on the NMDA receptor & blocks Na⁺ channels
  • possibly blocks the excitatory effects of glutamate

Adverse Effects:

  • GI issues
  • rare but fatal aplastic anemia → restricted for use only in extreme refractory epilepsy
17
Q

Topiramate (Topamax)

A

-used for partial sz, as an adjunct to tonic-clonic sz (add-on to phenytoin)

MOA: acts on AMPA receptors, blocks glutamate binding site, also blocks kainate receptors and Na⁺ channels and enhances GABA currents

Adverse Effects:

  • paresthesia (pins & needles)
  • fatigue
  • taste change
  • weight loss
  • difficulty concentrating
18
Q

Benzodiazepines

A
  1. Clonazepam (Klonopin)
    - used for absence sz (sometimes myoclonic)
    - most specific ADE among benzos- selective for GABA
    - sedating, may lose effectiveness to development of tolerance
  2. Diazepam (Valium) and Lorazepam (Ativan)
    - used as first-line treatment for status epilepticus (delivered IV-fast acting)
    - sedating
    - causes ataxia
    - behavioral changes
  3. Phenobarbital, Primidone (Myosoline)
    - used for partial sz, especially in neonates
    - look at page
19
Q

Tigabine (Gabitril)

A
  • interferes w/ GABA re-uptake
  • used to treat partial sz
  • uncommonly used

ADEs:

  • ↓ concentration
  • dizziness, somnolence, nervousness
  • chest pain, hypertension, edema, syncope, vasodilation
  • alopecia
  • speech disorder
20
Q

Vigabatrin

A
  • uncommonly used
  • treats partial sz & tonic-clonic sz as an alternative agent
  • irreversible inhibitor of GABA amino-transferase
  • enzyme responsible for the degradation of GABA
  • GABA released at synaptic site
  • enhances inhibitory effects

ADEs:

  • sedation
  • dizziness
  • wt gain
21
Q

Na⁺ Channels as AED Targets

A
  • neurons fire at high frequencies during seizures
  • action potentials generation is dependent on Na⁺ channels
  • use-dependent/ time-dependent Na⁺ channel blockers reduce high frequency firing w/o affecting physiological firing
22
Q

AEDs that act primarily on Na⁺ channels

A

Phenytoin, Carbamazepine
- block voltage-dependent Na⁺ channels at high firing frequencies (use dependent)

Oxcarbazepine

  • blocks voltage-dependent Na⁺ channels at high firing frequencies
  • also effects K⁺ channels
23
Q

Hydantoins:
Phenyoin (Dilantin)
Fosphenytoin (Cerebyx)

A
  • first line for partial seizures
  • some use for tonic-clonic seizures
  • Fosphenytoin- prodrug for phenytoin (used as IM)

MOA:

  • blocks voltage-dependent Na⁺ channel at high firing frequencies
  • highly protein bound (have to monitor blood closely)
  • induces P450 enzyme system

Adverse Effects

  • GI irritation
  • sedation
  • gingival hyperplasia
  • hirsutism
  • nystagmus
  • ataxia
  • dysarthria
24
Q

Iminostilbenes: Carbamazapine (Tegretol)

A

-tricyclic antidepressant used for partial sz & tonic-clonic sz

MOA:
-similar to phenytoin
induces P450 enzyme system → induces its own metabolism

Adverse Effects:

  • Sedating
  • agranulocytosis and aplastic anemia
  • leukopenia
  • hyponatremia
  • cardiac arrhythmias
  • CHF
25
Q

Iminostilbenes: Oxcarbazapine (Trileptal)

A
  • newer agent- related to carbamazapine
  • approved for monotherapy in partial sz

MOA:

  • same as carbamazapine
  • may also agument K⁺ channels
  • some CYP450 induction

Adverse Effects:
-sedating, but less toxic than carbamazapine

26
Q

Zonisamide (Zonergan)

A

-used as add-on for partial and generalized sz

MOA:
-blocks voltage-dependent Na⁺ channels and T-type Ca⁺⁺ channels

Adverse Effects:

  • Serious skin rash
  • suicidal ideation
  • metabolic acidosis
  • anemia, leukopenia
27
Q

Lamotrigine (Lamictal)

A

-add-on therapy or monotherapy for refractory partial sz

MOA:

  • inhibits glutamate release and (perhaps) Ca⁺⁺ channels
  • metabolism affected by valproate, carbamazapine, phenobarbital, phenytoin

Adverse Effects:

  • less sedating than other AEDs
  • severe dermatitis in children
28
Q

Ca⁺⁺ Channels as Targets

A
  • general Ca⁺⁺ channel blockers have not proven to be effective AEDs
  • absence sz are caused by oscillations b/t thalamus & cx that are generated in thalamus by T-type (transient) Ca⁺⁺ currents
29
Q

Succinimides:

Ethosuximide (Zarontin)

A

MOA:

  • acts specifically on T-type channels in thalamus
  • very effective against absence sz

Adverse Effects:

  • GI disturbances
  • less sedating
  • mov’t disorders
  • skin rashes
30
Q

Gabapentin (neurotin)

Pregabalin (lyrica)

A

-used in add-on therapy for partial and tonic-clonic sz

MOA:
-acts specifically on Ca⁺⁺ channel subunits called

31
Q

K⁺ channels as Targets

A
  • K⁺ channels have important inhibitory control over neuronal firing firing in CNS- repolarizes membrane to end action potentials
  • K⁺ channel agonists would ↓ hyperexcitability in the brain
  • only AED with known actions on K⁺ channels is valproate
32
Q

Carboxylic Acids:

Valproate (Valproic Acid)

A

-first-line for generalized sz, also used for partial sz

MOA:

  • acts of K⁺ channels to ↓ hyperexcitability in the brain
  • also blocks Na⁺ channels and enhances GABAergic transmission
  • highly protein bound
  • inhibits CYP450

Adverse Effects:

  • CNS depressant
  • GI disturbances
  • hair loss
  • weight gain
  • teratogenic (ADE on fetus)
  • heptotoxic
33
Q

Regulation of NT release on Anti-Epileptics

A
  • several AEDs have actions that result in the regulation of nt release from the pre-synaptic terminal
  • ie. lamotrigine in addition to their noted action on ion channels
  • levetiracetam appears to have as its primary action the regulation of nt release by binding to the synaptic vesicle protein SV2A
34
Q

Levetiracetam (Keppra)

A

-add-on therapy for partial sz

MOA
-regulation of nt release by binding to the synaptic vesicle protein SV2A

Adverse Effects
-CNS depression

35
Q

Lacosamide (Vimpat)

A

-used for partial onset sz as adjunctive therapy

MOA

  • enhances the number of Na⁺ channels entering into the slow inactivated state
  • regulates and reduces the long-term availability of Na⁺ channels

Adverse Effects

  • N/V/D
  • diplopia
  • dose adjust in pts with mild/mod hepatic impairment or severe renal impairment
36
Q

Anti-Epileptic Drug Interactions

A
  • many AED are notable inducers of cytochrome P450 enzymes and a few are inhibitors
  • *of the classics, phenytoin, carbamazipine, phenobarbital, and primidone are all strong inducers of cytochrome P450 enzymes**
  • valproate inhibits cytochrome P450 enzymes
37
Q

Treatment Considerations for Anti-Epileptic Drugs

A
  • most AEDs undergo complete or nearly complete absorption when given orally
  • fosphenytoin (prodrug) can be administered IM if IV can’t be established in cases of frequent repetitive sz
  • diazepam (also as rectal gel) been shown to terminate repetitive sz and can be administered by family members at home
  • phenytoin, fosphenytoin, phenobarbital, diazepam, lorazepam and valproate are available as IV prep for emergency use
  • AEDs metabolized in liver and excreted by kidneys
  • add-on therapy is often necessary to eliminate “break-through” or refractory sz
38
Q

Status Epilepticus

A
  • more than 30 minutes of continuous sz activity
  • 2 or more sequential szs spanning this period w/o full recovery b/t szs
  • medical emergency

Treatment

  • diazepam, lorazapam IV (fast, short acting)
  • followed by phenytoin, fosphenytoin, or phenobarbital (longer acting) when control is established
39
Q

Considerations in Rehab for Anti-epileptics

A
  • thorough medical hx!
  • monitor pt progress-keeping dosages w/in therapeutic window
  • schedule sessions around time of day when side effects (H/A, dizziness, sedation, GI disturbances) are mild
  • ataxia might impair pt’s ability to participate in various fxnal activities (start coordination exercises)
  • interventions that might exacerbate skin conditions should be avoided
  • depending on the seizure triggers some pts might do better in a quieter environment at the time of day when chance of seizure is minimal