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Anticonvulsants Flashcards

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1
Q

Epilepsy

A

spontaneous episodes associated w/ loss or disturbances of consciousness, usually but not always accompanied by characteristic body movements and always excessive EEG discharge

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2
Q

Seizure

A

transient alteration of behavior due to disordered, synchronous and rhythmic firing of a population of brain neurons

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3
Q

Focal or partial seizure

A

60% of epilepsies, originates in one hemisphere of brain, usually due to lesion: head trauma, tumor, stroke, hypoxia at birth, metabolic disorders, malformations, can progress to generalized seizures

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4
Q

Generalized seizures

A

originates from both hemispheres simultaneously, loss of consciousness

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5
Q

Status epilepticus

A

failure of seizure termination>5 mins

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6
Q

Tonic-clonic

A

loss of consciousness w/ tonic stiffening followed by clonic muscle activity

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7
Q

isolated tonic

A

mostly in children, increased tone in extensors

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8
Q

isolated clonic

A

mostly in small children and babies

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9
Q

Atonic

A

abrupt loss of all muscle tone; patients fall

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10
Q

Absence

A

hardest to treat, commonly seen in children, brief loss of awareness and behavioral arrest, inhibition of GABA receptors, activation of T-type Ca current leading to hypperpolerization

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11
Q

Myoclonic

A

sudden or split second, contraction of a muscle or group of muscles

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12
Q

Lennox Gastaut syndrome

A

difficult to control seizure disorder where pt usually has myoclonic, atonic, absence and tonic seizures

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13
Q

Pathophysiology of seizures

A

not well understood, imbalance between excitatory and inhibitory neurons

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14
Q

Non-pharm treatment

A

surgery, ketogenic diet, vagal nerve stimulator

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15
Q

Goals of AEDs

A

decrease seizures, minimize adverse effects of seizures

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16
Q

AEDs MOA

A

inhibit Na channels, inhibit Ca channels, potentiate K channels, increase GABA, decrease glutamate

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17
Q

Barbiturates

A

Phenobarbital, primidone (Mysoline), Prntobarbital (Nembutol), Methohexital (Brevitol)

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18
Q

Barbiturates MOA

A

binds to allosteric modulation site that is present at a/B subunits of GABA, coupled to Cl channels they open in presence of GABA permitting influx of Cl and hyperpolerizes cell, barbiturates cause cl channel to stay open

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19
Q

Phenobarbitol

A

effective in tonic-clonic, and focal seizures, DOC for neonatal seizures, IV/PO, cheap, can be monitored

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20
Q

ADRs of phenobarbitol

A

sedation, depression of mood, cognitive impairment, hepatoxicity, lots of DIs

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21
Q

Primidone (Mysoline)

A

major metabolite of phenobarbitol, DOC for essential tremor, second line for focal and tonic clonic, very sedating, sometimes status epilepticus, primary use for pentobarbital coma

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22
Q

Phenytoin (Dilantin) MOA

A

Na channel blocker that binds the inactive channel and inc the time it takes to recover to the active state, prolonged recovery time limits high-freq firing, some use in antiarrythmias

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23
Q

Phenytoin (Dilantin) indications

A

focal w/and w/out 2nd generalization, sometimes primary generalized tonic clonic, eizure prevention following neurosurgery, not effective for atonic, absence or myoclonic seizures

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24
Q

Phenytoin (Dilantin)

A

IV/PO must drug monitor, narrow therapeutic index, nonlinear kinetics, status: load w/ 15-20 mg/kg IV/PO, maintenance 100 mg PO TID to start, normal levels 10-10 mcg/ml, adjust for protein, many DI

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25
Phenytoin ADRs
sedation, nausea, nystagmus, dizziness, cog impair, ataxia, SJS, hepatic toxicity aplastic anemia, gingival hyperplasia, hirsutism, folate defiency and osteopenia
26
Fosphenytoin (Cerebyx)
IV prodrug of phenytoin, less ADRs, infused faster 150 mg/min, loading does 100 mg IV, IV/IM
27
Benzodiazepines
Diazepam (Valium), Lorazepam (Ativan), Midazolam (Versed), Clonazepam (Klonipin), Clobazam (Onfi)
28
Benzo MOA
bind to allosteric modulation site of GABA receptor, GABA linked to Cl channel, when GABA and Benzos are bound to receptors they follow more frequent opening of channels, and thus more hyperpolarization
29
Clonazepam (Klonopin)
only PO, for myoclonic, atypical absence seizures of lennox Gastaut syndrome, severe ADRs limit use, CIV controlled
30
Clonazepam (Klonopin) dose
.5-2 mg PO BID
31
Clobazam (Onfi)
only PO, for adjunct Lennox-Gastaut, epilepsy, CIV controlled, ADRs- somnolence, pyrexia, lethargy, upper respiratory infxn
32
Clobazam (Onfi) dose
based on wt, end dose 10-20 mg PO BID
33
Diazepam (Valium)
PO, IV and rectal (acute at home), CIV controlled, many active metabolites, long T1/2
34
Diazepam (valium) dose
10-20 mg, rectal .2 mg/kg
35
Lorazepam (Ativan)
IV/PO, IV DOC for status, also acute seizures, PO rare for chronic, better options
36
Lorazepam (Ativan) dose
2 mg IV until controlled, maintenence dose .5 mg PO BID
37
Midazolam (Versed)
IV, refractory status last line, short T1/2 requires continuous infusion to maintain therapeutic levels, usually used for sedation
38
Succinimides
Ethosuximide (Zarontin), Methsuximide (Celontin)
39
Ethosuximide (Zarontin)
first absence seizure med, unknown MOA (block voltage dependent T-type Ca channels in thalamus), only effective for treatment of absence (DOC)
40
ADRs of Ethosuximide (Zarontin)
GI intolerance, sedation, dizziness, irritability, aggression, and extrapyramindal symptoms
41
The "Zepine" MOA
prolongs refractory period of voltage gated Na channels, inhibits voltage gated Ca channels, limits sustained high frequency neuronal firing of action potentials in a manner similar to PHT
42
Carbamazepine (Tegretol)
for partial seizures, generalized tonic/clonic, trigeminal neuralgia, acute mania, migraines, not for absence, myoclonic or atonic seizures, lots of DI, induces its own metabolism
43
Carbamazepine (Tegretol) dose and ADRs
200 mg BID, hyponatremia, dizziness, somnolence, ataxia, nystagmus, nausea, diplopia, SJS, leukopenia, agranulocytosis, aplastic anemia, hepatic toxicity
44
Oxycarbazepine (Trileptal)
developed to limit ADRs, metabolized to monohydroxy derivative which exerts the anticonvulsant effect, for monotherapy of add-on for focal seizures, few DI
45
Oxycarbazepine (Trileptal) ADRs and dose
150 mg PO BID-600 PO BID (2400mg/day max), dizziness, somnolence, ataxia, nystagmus, nausea, diplopia, rash, hyponatremia
46
Eslicarbazepine (Apriom)
brand new, 400-800 mg PO daily, for partial onset seizures as adjunct, same ADR and DIs
47
Valproate
Valproic Acid (Depakene), Divalproex (Depakote), IV/PO, broad spectrum, tonic/clonic, absense, myoclonic, focal, status, mania, migraine prevention/tx, many DI w/ other AEDs
48
Valproate MOA
inc GABA at synaptic sites, inc synthesis and dec degradation, reduced sustained rapid firing consistent w/ effect on Na channels, reduces excitation mediation by NMDA type glutamate receptors, blocks voltage dependent T-type Ca in peripheral ganglion
49
Valproate Dose
initial 10-15 mg/kg/day, load 1000 mg IV, max 50-60 mg/kg/day, normal maintenance 500mg PO BID, normal therapeutic 50-100 mcg/ml
50
Valproate ADRs
GI upset, sedation, cog impairment, ataxia, dizziness, weight gain, hair loss, hepatotoxic, pancreatitis, thrombocytopenia, encephalopathy, teratogenicity, PCOS
51
Felbamate (Felbatol)
Na channel blocker, non-NMDA glutamate receptor antagonist, use for focal seizures, Lennox-Gastaut syndrome, atonic seizures, use limited by ADRs
52
Gabapentin (Neurontin)/Pregabalin (Lyrica)
increases GABA synthesis, not very effective as anticonvulsant, for neuropathic pain, renally eliminated, 300 mg PO BID up to 1200 mg PO TID, gaba very sedating, pregabalin not as much (but dea controlled?)
53
Lamotrigine (Lamictal) MOA
blocks voltage dependent Na channels leading to decrease in glutamate release, blocks influx through voltage dependent Ca channel, enhancing hyperpolarizing K current
54
Lamotrigine (Lamictal) uses and ADRs
monotherapy or add on for all seizure, DOC bipolar, DOC during pregnancy, mood-elevating, dizziness, migraines, tremors, SJS (but not if titrate slowly)
55
Topiramate (Topamax) MOA
exact MOA unknown, likely effects Na channels, glutamate receptors and GABA
56
Topiramate (Topamax) Uses/Dose
25 mg PO BID up to 400 mg/day, monotherapy/add on for focal/ tonic/clonic, add on for lennox gastaut, ineffective for ansence, migraine prevention, wt loss
57
Topiramate (Topamax) ADRs
Cog impairment, sedation, behavior symptoms, peripheral paresthesis, nephrolithiasis, angle-closure glaucoma
58
Zonisamide (Zonegran)
reduces current through voltage-dependent Na channels, impairs high-freq firing of action potentials, blocks T-type Ca channels, used for mono/add on for generalized seizures
59
Levetiracetam (Keppra)
Unknown MOA, but unique, 500 mg PO BID up to 3000mg/day, IV/PO, focal, myoclonic, add on for status, seizure prevention in brain tumors, renally eliminated, no known DI, frequent in peds
60
Levetiracetam (Keppra)
generally well tolerate, does not need to be titrated, fatigue, irritability, psychosis, depression
61
Vigabatrin (Sabril)
inhibits GABA transaminase, inc GABA, for focal/ infantile spasms (DOC), BBW for vision loss
62
Ezogabine (Potiga)
unique MOA, neuronal K channel opener, stabilizes channels in open formation resulting in suppression of epileptic activity, for partial seizures, new safety alert for vision loss
63
Lacosamide (Vimpat)
slow inactivation of voltage-gate Na channels, indicated for partial onset seizures, IV/PO, neuropathic pain, dizziness, HA, nausea, diplopia, dose dependent PR interval prolongation
64
Rufinamide (Banzel)
prolongs refractory period of voltage-gated Na channels, for lennox-gastaut in pts >4 yo, cause sedation, nausea, HA, valproic acid will inhibit metabolism, decrease dose if using together
65
Generalized tonic clonic DOC
valproate, Levetiracetam, Fosphenytoin, Lorazepam, also Phenobarbital, Carbamazepine, Oxcarbazepine, phenytoin, topiramate
66
General absence DOC
ethosuximide, valproate, also levetiracetam, clonazepam, lamotrigine
67
Focal or partial DOC
carbamazepine, Oxcarbazepine, levetiracetam, also phenobarbital, phenytoin, topiramate, lacosamide
68
Myotonic DOC
valproate, levetiracetam, also rufinamide, clobazam
69
Status epilepticus
Lorazepam, Diazepam, also fosphenytoin or phenobarb for prolonged
70
Lennox gastaut
valproate also clobazam, topiramate, rufinamide

Pharmacology (61 decks)

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