Anticonvulsants

Front 1

Anti-epileptic drugs- major mechanisms

Back 1

1. inhibition of Na+ channels in neuronal membrane
2. inhibition of Ca++ channels
3. enhanced GABA neurotransmission or decrease degradation of GABA
4. glutamate receptor antagonist

Front 2

almost all antiepileptic drugs are associated with...

Back 2

-CNS depressing effects
-some tolerance to these effects develops over 7-10 days

Front 3

Carbamazepine (Tegretol)

Back 3

-MOA: Na channel blocker
-oral
-metabolized by YP 3A4; autoinduction (over a couple of wks will accelerate or induce its own metabolism)
-Cat D
-used for: partial seizures esp complex, tonic clonic seizures, mood stabilizer

Front 4

Carbamazepine AE

Back 4

1. black box warning - frequent CBC monitoring secondary to few causes of aplastic anemia and leukopenia
2. rash -->SJS (more common in asians- check HLAB 1502)
3. blurry vision
4. nystagmus
5. ataxia
6. dizziness
7. GI

Front 5

Carbamazepine DI

Back 5

1. erythromycin
2. clarithromycin
-serum drug levels

Front 6

Oxycarbazepine (Trileptal)

Back 6

-similar structure and MOA as carbamazepine
-more $ but better tolerated
-not autoinduction
-first line for partial and general tonic clonic, mood stabilizer

Front 7

Phenytoin (Dilantin)

Back 7

-MOA:alters Ca++ uptake, alters N+/K+ pump slows rate of Na+ channels recovery
-liver metabolism
-for generalized tonic clonic seizures
-status epilepticus, prophlaxis and tx of seizures in neurosurgery
-write for the name

Front 8

Dilantin AE

Back 8

1. lethargy, fatigue, incoordination
2. drowsiness, ataxia
3. nystagmus
4. hypotension (IV)
5. gingival hyperplasia
6. endocrine and metabolic: hirsuitism, coarsening of facial features,osteoporosis - chronic effects
-interactions with other AEDs
-preg cat D

Front 9

Valproic acid (Depakene)

Back 9

-MOA: affects Na+ channels and may affect GABA metabolism
-Depakote- enteric coated- better on stomach
-Depakene
-used for generalized absence seizures and myoclonic seizures, partial and generalized tonic clonic

Front 10

Valproic acid AE

Back 10

1. dizzy, tremor, HA, insomnia, blurred vision-MOST COMMON
2. hepatotoxicity early in course!
3. GI
4. wt gain
5. alopecia
6. thrombocytopenia
7. pancreatitis
DI: other AEDs
-Cat D

Front 11

Phenobarbital and Primidone

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-MOA: barbiturate bind to receptors which enhance inhibitory effects of GABA on postsynaptic neurons
-IV>IM>PO
-P450 inducer
-uses: neonatal seizures, generalized tonic clonic and partial seizures

Front 12

Phenobarbital

Back 12

-CNA depressant effects: drowsy, somnolence
-impairs cognitive function and may paradoxically stimulate kids
-rashes
-enzyme inducer and may increase elimination of drugs metabolized by hepatic enzymes
-cat D

Front 13

Topiramate (Topamax)

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-MOA: multiple actions- blocks Na, channels, enhances GABA and decreases glutamate transmission
-role for partial seizures and generalized tonic clonic
-cat C

Front 14

Topiramate AE

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1. ataxia
2. memory impairement
3. parethesias
4. memory difficulties, word finding difficulties
5. wt loss!
6. nephrolithiasis (drink lots of H2O)
-fewer DIs

Front 15

Ethosuximide (Zarontin)

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-MOA: reduces Ca++ currents in thalamic neurons
-first line for absence seizures
-rapid GI absorption, liver metabolism, mostly renal excretion

Front 16

Ethosuximide AE

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1. N/V
2. anorexia
3. drowsiness, fatigue, lethargy
4. rarely rash, hypersensitivity rxns

Front 17

Lamotrigine (Lamictal)

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-MOA: unknown
-oral
-used for adjunctive and monotherapy for partial epilepsy
-cat C

Front 18

Lamictal AE

Back 18

1. diplopia
2. HA
3. ataxia
4. BB warning = rash!
5. DI: valproic acid use increases risk of rash

Front 19

Gabapentin (Neurotin)

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-enhances GABA neurotransmission and may modulate Ca++ channels
-po dosing
-Cat C
Uses:
-monotherapy and adjunctive therapy of partial seizures
-neuropathic pain
-bipolar

Front 20

Gapapentin AE

Back 20

1. fatigue, dizzines and ataxia
2. tremor and nystagmus
3. wt gain and edema
4. better tolerated overall
5. no major DI

Front 21

Levetiracetam

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-new for partial seizures in adults
-also used for primary generalized tonic-clonic (PGTC) seizures in adults and children 6 years of age and older with idiopathic generalized epilepsy
AE: asthenia, somnolence, dizziness
-well tolerated

Front 22

Tiagabine

Back 22

-adjunctive for partial seizures with other drugs
-inhibits GABA reuptake
-AE: dizziness, tremor, somnolence, may increase absence seizures

Front 23

Zonisamide (Zonegran)

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-used as adjunct for partial seizures
-MOA: Ca+ and Na+ channel blocking
-AE: ataxia, anorexia, somnolence, nervousness

Front 24

Pregabalin, Lyrica

Back 24

-uses:
1. partial seizures
2. fibromyalgia
3. neuropathic pain
-AE: dose-dependent
1. dizziness
2. somnolence
3. dry mouth
4. blurred vision
5. wt gain

Front 25

Rufinamide (Banzel)

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-modulation of the activity of Na+ channels and in, particular prolongation of the inactive state of the channel
-adjunctive tx of seizures assoc with Lennox-Gastaut syndrome in kids 4 yrs and older and adults
-AE: QT shortens, ataxia, dizziness, nausea

Front 26

Lacosamide (Vimpat)

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-tx of partial seizures
-AE: PR prolongation ,dizzy, ataxia, N/V, vertigo, blurry vision
-cat C

Front 27

New onset epilepsy

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-standard AED vs. new AED --> can use standard or new drugs, gabapentin, oxycarbazepine, lamotrigine or topiramate
-better tolerated but more $$

Front 28

Refractory seizures

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-partial: Oxycarbazapine and topiramate are useful monotherapy
-generalized: Topiramate may be used for refractory tonic clonic seizures

Front 29

women/pregnancy and AEDs

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-Many AEDs induce hepatic enzymes: Use higher dose oral contraceptives and/or other methods of contraception
-preg cat D: phenytoin, carbamazepine, valproic acid
-Cat C: new AEDs

Front 30

When to treat?

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-2+ seizure or high risk for recurrent seizures
-recurrent seizures require tx
-try a single drug
-Substitute (preferably) or add another drug if patient cannot tolerate or seizures are not controlled
-stop: when pt is seizure free for 2-4yrs

Front 31

Generalized tonic clonic

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Phenytoin
Carbamazepine
Phenobarbital
Valproate

Front 32

Generalized non-convulsive

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Valproate
Ethosuximide
Carbamazepine
Clonazepam (Klonopin) – a benzodiazepine

Front 33

Partial seizures

Back 33

Carbamazepine, phenytoin, valproate (OLD AEDs)
New AEDs as discussed in previous slides

Front 34

Status epilepticus

Back 34

-seizure activity for >30 min
-give thiamine and glucose
-Lorazepam or diazepam followed by phenytoin loading dosage
-If no control add phenobarbital