Wq Pharm - Anti-Seizure Drugs

Front 1

Partial szs

Begin at:

Subtypes:

Back 1

focally in cortical site

Simple partial, comples partial, partial with tonic-clonic sxs

Front 2

What does a simple, partial sz look like (2)?

A complex partial (3)?

Back 2

jerking for ~20 secs. No LOC

LOC < 2mins, automatic mvmnts, begins in temporal lobe.

Front 3

What does a partial sz with tonic-clonic mvmnts look like (2)?

Back 3

LOC with muscle contractions/relaxations

Front 4

What exactly happens during partial szs?

What types of drugs are effective for them?

Back 4

neurons fire at high freq.

Drugs that prolong the inactivation phase (these are usually effective without compromise of normal transmission)

Front 5

In general szs, both ___ are involved.

What are the three subtypes?

Back 5

Hemispheres

tonic-clonic/grand-mal, absence/petite mal, myoclonic

Front 6

What do generalized tonic-clonic szs look like (2)?

Absence szs?

Myoclonic?

Back 6

LOC, mm contractions

<30 secs of staring & inactivity.

brief shock-like activity in one extremity or generalized

Front 7

What actually happens during absence szs?

What type of channel is responsible for these?

Back 7

discharges begin at thalamus and spike/wave at 3 Hz.

T-type voltage gated Ca channel. (causes T-current)

Front 8

What are the hypotheses of sz generation in general (2)?

What is kindling?

Back 8

Underactivity of GABA neurons or overactive glutamate transmission

Experimental hyperexcitable state after stim of amygdala and limbic stxs.

Front 9

What tx prevents kindling?

Back 9

inhibition of NMDA recs/rls.

Front 10

What anti-sz drugs prolong the inactivation period via Na channels (4)?

What two drugs tx the T-type Ca channel issues in absence szs?

Back 10

phenytoin, carbemazepine, lamotrigine, valproic acid

valproic acid, ethosuximide

Front 11

Which anti-sz drugs increase GABA activity, leading to hyperpol of neurons by opening Cl- channels (2)?

Back 11

phenobarbitol & benzos

Front 12

How often is anti-sz medicine effective?

Better to use monotx or combo?

Why must drug plasma levels be regularly monitored?

Back 12

Only in 50% of pts.

Mono. Try not to combine.

Must balance tx efficacy with side effects.

Front 13

In general, how are anti-sz drugs metabolized?

Which ones induce P450 instead (3)?

Back 13

slowly, by the liver, by P450

Phenytoin, carbemazepine, phenobarbitol

Front 14

Phenytoin

Used for:

Useless for:

Added benefit:

Back 14

Effective for partial & gen tc szs

absence szs

Non-drowsy

Front 15

Phenytoin

Mech:

Back 15

Prolongs inactivation period

Front 16

Phenytoin - PHKs

Abs:

IM inj issue:

PP bind:

Back 16

Abs varies

phenytoin is insoluble, so use soluble fosphenytoin for IM inj

PP bind 90%

Front 17

Phenytoin - PHKs

Elimination (3):

Consequence of elimination issue:

Back 17

is dose dependent. 1st order at low dose, zero order at high dose.

small dose changes = large blood concentration changes.

Front 18

Phenytoin - PHKs

Takes how long to reach steady state (2)?

t1/2:

Therapeutic range:

Back 18

5-7 days a low dose, 4-6 wks at high doses

12-36 hrs

Small: 10-20 microg/mL

Front 19

Phenytoin - toxicity

CNS (5):

Preg:

Back 19

Nystagmus, dbl vision, sedation, ataxia, periph neuropathy

Cat D teratogen

Front 20

Phenytoin - toxicity

20-30% of pts get:

Others (3):

Back 20

*Gingival hyperplasia & hirsuitism in 20-30%*

Coarse facial features, HS rashes, osteomalacia secondary to Vit D & Ca issues

Front 21

Phenytoin - CIs

Displaced by (2):

Metab inhib by:

Metab increased by:

Back 21

phenylbutazone or sulfonamides

other drugs metab by same enzymes = increased phenytoin

carbemazepine

Front 22

Phenytoin - CIs

Dec metab of:

Inc metab of:

Back 22

warfarin

BCPs

Front 23

Carbemazepine

Used in (3):

Mech:

Benefit:

Back 23

DOC for partial and gen tc szs, mood-stabilizer, tx of trigeminal neuralgia

prolongs inactivation period

non-drowsy

Front 24

Carbemazepine - PHK

Abs:

Liver enzyme:

Induces metab of (2):

Back 24

Varies. give after meal

Induces CYP3A

BCPs, itself

Front 25

Carbemazepine - PHK

Therapeutic range:

Drug similar to it:

Back 25

small: 6-12 microg/mL

oxcarbazepine

Front 26

Carbemazepine - Toxicity

CNS (3):

Blood (1):

Skin:

Preg:

Back 26

Dbl vision, ataxia, sedation at high doses

Idiosyncratic blood dyscrasias (listed in another card)

HS rash (poss SJ, esp in asians)

Cat D teratogen

Front 27

List the idiosyncratic blood dyscrasias that may be seen with carbemazepine toxicity (3)?

Back 27

aplastic anemia, agranulocytosis, leukopenia

Front 28

Carbemazepine - CIs

It inc metab of (7):

These increase it's metab (3):

Back 28

phenytoin, primidone, ethosuxamide, valproic acid, clonazepan, haloperidal, BCPs

phenobarbitol, phenytoin, & valproic acid

Front 29

Carbemazepine - CIs

These dec it's metab (4):

Back 29

cimetidine, fluoxetine, isoniazid, erythromycin

Front 30

Phenobarbitol

Uses (2):

Mech:

Metabs to:

Preg:

Back 30

Anticonvulsant, sedative

Prolongs opening of Cl- channel at GABAa rec.

primidone

Cat D

Front 31

Vigabatrin

Use:

Status:

Mech:

Back 31

partial & gen tc szs, infantile spasms

Investigational

Irrev inhib of GABA transaminase = in synaptic GABA

Front 32

Vigabatrin

Use restricted due to what risk:

Back 32

May cause perm visual damage in 30%.

Front 33

Vigabatrin

Side effects (5):

CI:

Back 33

drowsy, dizzy, weight gain, agitation, confusion

Mental illness

Front 34

Lamotrigine

Uses (3):

Mech:

Back 34

partial szs adjunct, absence szs, bipolar

Prolongs inactivation period. May also work on Ca ch. (absence szs)

Front 35

Lamotrigine - toxicity

CNS(4):

Skin:

Preg:

Back 35

Dizzy, HA, dbl vision, somnolence

HS rxn - poss fatal in peds

Cat C - not evaluated

Front 36

Gabapentin

Uses (4):

Mech:

Analogue of:

Back 36

Adjunct for partial & gen tc szs, neuropathic pain, tx bipolar, anxiolytic

Mech unknown.

GABA analogue, but not GABA rec agonist.

Front 37

Gabapentin

Acts like:

May enhance:

Back 37

valproic acid

GABA release

Front 38

Gabapentin - PHKs

Dose range:

Excretion/kinetics:

t1/2:

Back 38

Seriously huge dose range

RExc with linear kinetics

5-8 hrs

Front 39

Gabapentin - Side effects

CNS (5):

GI:

Preg:

Back 39

Dizzy, sedation, ataxia, HA, tremor

Weight gain

Cat C: teratogenic in animals

Front 40

Levetiracetem

Uses (3):

Mech (long):

Back 40

partial, gen tc, myoclonic szs

Binds to SV2A - a synaptic vesicle protein - and reduce glutamate rls while increasing GABA rls

Front 41

Levetiracetem

Side effects:

Metab is NOT:

Back 41

dizzy, somnolence, ataxia, asthenia

via P450, so less interactions

Front 42

Topiramate

Uses (5):

Back 42

all szs, West syndrome, Lennox-Gestaut syndrome, migraines, weight loss

Front 43

Topiramate

Mechs (3):

In general, it inhibits:

Back 43

Blocks Na channels, enhances GABAa currents, limits glutamate reactivation

inhibits the spread of szs currents

Front 44

Topiramate PHKs

Excretion:

t1/2:

Inc metab of:

Back 44

RExc (unchanged in urine)

20-30 hrs

BCPS

Front 45

Topiramate

Side Effects (4):

Preg:

Back 45

dizzy, sedation, nervous, confusion

Cat C: teratogenic

Front 46

Tiagabine

Use:

Mech:

Back 46

adjunct for partial szs

Inhibition of GABA uptake in neurons & glia = prolongs action

Front 47

Tiagabine - PHKs

Abs:

PP bind:

t1/2:

Interactions:

Back 47

Oral: well abs

High PP bind

short

Rare

Front 48

Tiagabine - Toxicity

CNS (4):

Behavioral:

Skin:

Preg:

Back 48

nervousness, diff concentrating, dizziness, tremor

depression

Rash

Cat C teratogenic

Front 49

Ethosuxamide

Use:

Dose freq:

Mech:

Back 49

DOC for absence szs

BID to decrease GI sxs

Reduces T-current in thalamus

Front 50

Ethosuxamide

Abs:

t1/2:

Preg:

Back 50

Oral: well abs

~ 40 hrs (median)

Cat C: not tested

Front 51

Ethosuxamide

CI:

Back 51

valproic acid decreases the clearance of ethosuxamide

Front 52

Ethosuxamide - toxicity

GI:

Other (5):

Dangerous:

Back 52

GI upset, pain

Lethargy, HA, dizzy, hiccup, euphoria

Steven's Johnson

Front 53

Valproic acid

Uses (2):

DOC for:

OK for:

Back 53

Absence & gen tc szs

times when both types of above szs occur in same pt

Partial szs

Front 54

Valproic acid

Non-sz uses (2):

Gen mech:

Preg:

Back 54

mood stabilizer, prev migraines

Blocks high freq repetitive firing (prob Na channel blocker)

Cat D teratogen

Front 55

Valproic acid

Poss mechs (3):

Back 55

Na channel blocker, inc synth of GABA, inc K conductance to hyperpol PMs

Front 56

Valproic acid - PHKs

Abs:

Often given:
t1/2:

Back 56

Oral: well abs, but delayed by food

after meals to dec toxicity

Front 57

Valproic acid - CIs

Inhibs metab of:

Displaces:

Decreases clearance of:

Back 57

itself at low doses, phenytoin, carbemazepine, phenobarbitol (coma)

phenytoin

ethosuxamide

Front 58

Valproic acid - Toxicity

GI (4):

CNS (2):

Liver:

Back 58

GI upset, GERD, weight gain, inc appetite

Sedation, tremor

Hepatotoxic, exp with many Rx.

Front 59

Diazepam

Use for szs:

Also used in this way:

Preg:

Back 59

IV for status epilepticus

Lorazepan

Cat D

Front 60

Clonazepam

Uses (4):

Common issues (2):

Preg:

Back 60

Benzo, abs szs, myclonic szs, infantile spasms

sedation and development of tolerance to anti-sz effect

Cat D fetal malformation 1st trimester

Front 61

What is Stevens-Johnson syndrome?

AKA:

Sxs (5):

Back 61

HS AI skin rash

erythema multiforme

Rash, arthritis, AGN, CNS issues, myocarditis

Front 62

What drugs may cause Stevens-Johnson syndrome (7)?

Back 62

phenytoin, carbemazepine/oxcarbazepine, phenobarb/primodine, lamotrigine, tiagabine, ethosuxamide, valpric acid

Front 63

What anti-sz drugs are Cat C (4)?

Back 63

Lamotrigine, gabapentin, topiramate, tiagabine

Front 64

What anti-sz drugs are Cat D(6)?

Back 64

phenytoin, carbemazepine/oxcarbazepine, phenobarb/primodine, ethosuxamide, valproic acid, benzos

Front 65

What is a behavioral risk for all anti-sz meds?

Back 65

Higher risk of suicidal ideation.