anticonvulsants 49/50 Flashcards Preview

Pharm > anticonvulsants 49/50 > Flashcards

Flashcards in anticonvulsants 49/50 Deck (46):
1

Phenobarbital (Luminal®)

anti epileptic drug: barbiturate, original, cheap, effective

tonic-clonic and partial seizures
potentiation of synaptic inhibition via GABAa receptor

2

Phenytoin (Dilantin®, Diphenylan®)

anti epileptic drug

monotherapy generalized tonic-clonic and partial seizures

Block of voltage gated sodium channels (promote inactive state)

zero-order kinetics

3

Carbamazepine (Tegretol®, Carbatrol®)

anti epileptic drug

Block of voltage gated Na+ channels (promote inactive state)

monotherapy generalized tonic-clonic and partial seizures (also used in manic-depressive patients)

self-induced metabolism, also, metabolism increased by pheonbarb/phenytoin

4

Ethosuximide (Zarontin®)

anti epileptic drug

mono therapy for *absence seizures* (altered Ca2+ channel function in thalamus)

Block of T-type calcium channels located on the postsynaptic membrane (thalamus)

5

Valproic acid (Depakote®, Depakene®)

anti epileptic drug

monotherapy, tx both *absence* and tonic-clonic seizures (*ALL*)

Block of voltage gated Na+ channels (promote inactive state)
AND
Block of T-type calcium channels located on the postsynaptic membrane

increases GABA synthesis

(off-label uses)

6

Fosphenytoin (Cerebyx®)

anti epileptic drug

water-soluble pro-drug of phenytoin used for treating status epileptics (given IV)

7

Gabapentin (Neurontin®)

Newer anti epileptic drug

GABA molecule bound to lipophillic hexane ring (crosses BBB)

DOES NOT actually interact with GABA receptor, but suppress neuronal activity
binds to L-type Ca channels

Adjunctive tx partial +/- genalized secondary seizures; but mostly used for neuropathic pain

**Not metabolized, excreted unchanged in urine (RFTs before tx)

SE: fatigue, ataxia

(similar drug: Pregabalin (Lyrica®))

8

Oxcarbazepine (Trileptal®)

Newer anti epileptic drug

Block of voltage gated Na+ channels (promote inactive state)

monotherapy/adjunctive treatment partial seizures

like carbamazepine, but does not auto induce, but still incr. metabolism of OCTs

9

Lamotrigine (Lamictal®)

Newer anti epileptic drug

Monotherapy and adjunctive treatment partial- and generalized tonic/clonic seizures; LGS. Considered a “broad spectrum” AED

prolong rate of recovery of voltage-gated Na+ channels from inactivation, inhibit Ca to lesser extent

10

Topiramate (Topomax®)

Newer anti epileptic drug

Monotherapy and adjunctive therapy for partial and tonic/clonic seizures, LGS. Considered a “broad spectrum” AED

Inhibit Na channels and AMPA-kainate receptors enhance GABA receptors

11

Levetiracetam (Keppra®)

Newer anti epileptic drug

Adjunctive treatment for partial- and tonic/clonic seizures in adults and myoclonic seizures in children; IV preparation for status epileptics

may prevent presynaptic glutamate release

*highest safety margin*
highest therapeutic index
3-D "printable" drug

12

simple partial seizure

single site within the cortex
preservation of consciousness, short duration 20 – 60 sec

focal motor (e.g. one side of face may twitch)
Jacksonian (“marching” seizure, e.g. muscle twitching “running” up the arm)
somatosensory (varied responses; smelling sulfur, crawling sensation on skin, narrowing of visual field)

13

complex partial seizure

single site within the cortex
gradual loss of consciousness, 30 sec – 2 min

may begin with simple seizure, hallucination, strong emotions followed by automatisms (lip smacking, hand wringing, etc)

14

EEG can determine ??



type of seizure

15

Of the ~10 electrodes placed on the head for an EEG:

if only 1-2 electrodes display synchronous activity during seizure, what type ??

all EEG electrodes will display synchronous activity during a ??

partial seizure

generalized seizure

16

if all EEG electrodes display synchronous activity during a seizure

generalized seizure

17

generalized seizure

simultaneously in both hemispheres of brain (40% of all seizures)


18

absence (generalized)

sudden loss of consciousness, less than 30 sec

staring and blinking (3/sec)
body may remain active
ADHD, impaired learning

19

tonic-clonic (grand mal, gen)

sudden loss of consciousness, 1.5 to 2.5 min

20 sec of muscle rigidity followed by 1 – 2 min of rhythmic muscle contractions (clonic)

injury when falling during tonic stage, loss of bowel control

20

Phenobarbital (Luminal®) SEs

sedation, irritability/hyperactivity (kiddos), rash

*metabolized by CYP2C9, induction of CYP3A4--> inc. metabolism of OCTs and *teratogenic*

21

anticonvulsant drug MOA

reduce neuronal activity

22

drugs that enhance inhibitory effects of GABA

Barbs (Phenobarbital and primidone) and benzos (clonazepam, diazepam) increase GABA effects at GABAa

tiagabine: inhibit the re-uptake of GABA

vigabatrin: irreversible inhibitor of the GABA-degrading enzyme GABA transaminase

23

monotherapy will sufficiently control seizures for

70% of epileptic pts

24

original seizure tx

bromides

25

barb less effective than phenobarbital

SEs??

primidone

dizziness, nausea, nystagmus, ataxia (dec. firing)

26

Phenytoin SEs

gingival hyperplasia

SJS: only in first few months of tx

interact with warfarin and OCTs and may cause birth defects

27

Carbamazepine SEs

Acute: stupor, coma, hyperirritability convulsions

Chronic: drowsiness, vertigo, ataxia, blurred vision. Induces CYP3A4 resulting in increased drug metabolism (e.g. oral contraceptives)

28

benzos can be used for ??

adjunctive treatment only of absence seizures and juvenile myoclonic seizures

29

newer AEDs

lack serious side effects (less SJS)

do not induce liver enzymes (fewer drug-drug interactions)

less efficacious

mostly approved for adjunctive treatment (combo tx)

30

Lennox-Gustaut syndrome

Childhood-onset epilepsy

Severe cognitive dysfunction

Multiple seizure types including atonic or “drop” seizures (cause of injury)

Resistant to drug therapy (tx with Felbamate)

Mortality rates 3 – 7%

ketogenic diet

31

partial seizure tx

(or secondarily
generalized)

carbamazepine
phenytoin

alternative: lamotrigine (broad-spec)
valproic acid

32

generalized: absence seizure tx

Ethosuximide
Valproic acid*

alternative: Clonazepam

33

generalized: tonic-clonic tx

Carbamazepine
Phenytoin
Valproic acid*

alternatives:
Lamotrigine*
Topiramate*

34

Status Epilepticus

a series of seizures (any type) where full recovery from one seizure does not occur before onset of next seizure

20% mortality rate

35

Status Epilepticus tx

lorazepam IV

IV fosphenytoin (Cerebyx®) (water soluble prodrug of phenytoin-which would irritate veins)

levetiracetam (alternative to fosphenytoin)

phenobarbital and valproic acid (Depacon®)

36

long term use of AEDs may cause

osteoporosis:
altered vitamin D metabolism in the liver-->lower bone density

37

AEDs: OCT interactions


safe for preggos??


specifically ??




most common offending drug ??

3X higher failure rate of the contraceptive

NO, 2 – 3 fold increase in birth defects

neural tube formation abnormalities resulting in facial and cranial deformities

phenytoin (all AEDs may cause similar birth defects)

38

To reduce the likelihood of neural tube birth defects the patient should be given ???

folate (0.4 mg/day) throughout pregnancy

vitamin K (10 mg/day) during last month of gestation to help reduce newborn blood coagulation problems/Vit K deficiencies

39

treating epilepsy with ??? is controversial

generic drugs, use brand names

40

teratogenic AED

valproic acid

41

for pregnant/soon to be pregnant pts...

do not discontinue tx (do not want break thru seizures)
but reduce to mono therapy and monitor drug plasma levels/seizure activity, lowest dose possible is desired

42

ethosuximide SEs

Nausea, vomiting, anorexia
CNS drowsiness, lethargy, euphoria
SJS, aplastic anemia

43

Valproic acid SEs

GI nausea, anorexia
CNS sedation, ataxia, tremor
Increase in hepatic blood enzymes (40%)
Hepatic toxicity in patients

44

Lamotrigine SEs

dizziness, ataxia, blurred vision, nausea
Rash and SJS when used in addition to other AEDs

45

Topiramate SEs

Ataxia, fatigue, somnolence, weight loss
Reduces plasma levels of estradiol and oral contraceptives

46

Levetiracetam SEs

somnolence, dizziness, asthenia , no drug-drug interactions