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Flashcards in Know this sz Deck (30):
1

Valproate

Efficacy

Broad spectrum agent with efficacy against the most common seizure types

Pharmacokinetics

Administered as enteric-coated and delayed-release formulations

Inhibits metabolism of other AEDs: phenytoin, lamotrigine, carbamazepine, phenobarbital, ethosuximide

2

Dose-related GI upset (nausea-vomiting, pain)

Weight gain common

Black Box Warnings
-Hepatic failure
-Life-threatening pancreatitis – monitor symptoms
-Teratogenic effects (neural tube defects) – weigh benefit-risk

Valproate

3

Status Epilepticus Treatment Options:

Initial therapy IV diazepam (lorazepam or midazolam) until seizures stop or 20 mg given

Then start phenytoin or fosphenytoin slow infusion

If seizures persist IV phenobarbital until seizures stop

If seizures still continue, pentobarbital or propofol infusion with pressor support

4

Drug of choice in absence seizures


Ethosuximide

5

Ethosuximide

Adverse Drug Reactions – generally few side effects

Dose-related gastric distress most common (NV, pain)

Less common: transient lethargy-fatigue, dizziness, headache

6

Mechanism - Efficacy

Precise mechanism unknown - affects Ca++ channels

1st line in treatment of generalized tonic-clonic seizures

Levetiracetam

7

Levetiracetam ADRs

Somnolence, asthenia, dizziness

Low incidence of cognitive effects

No CYP450 metabolism - minimal DDIs

8

Effects on VSSCs (suppress repetitive APs) and VSCCs (↓ Glu release) - broad spectrum

1st line for partial or generalized seizures - better tolerated than phenytoin or carbamazepine

Lamotrigine

9

ADRs Lamotrigine

Similar to phenytoin (lower incidence): diplopia, ataxia, dizziness, skin rashes, sedation

10

Phenytoin

Very effective against partial and tonic-clonic seizures

11

Phenytoin Pharmacokinetics

Oral absorption is formulation dependent – concern with generic switching

IM absorption erratic (better with prodrug Fosphenytoin)

Zero-order (saturation) metabolism in therapeutic range

**Strong inducer of CYP450 enzymes --> DDIs

12

Phenytoin Adverse Drug Reactions

Nystagmus-diplopia-ataxia-sedation --> dose-related

Rash; gingival hyperplasia-hirsutism develop gradually

Long-term use --> osteomalacia, peripheral neuropathy

13

Carbamazepine Efficacy

A drug of choice for partial seizures

Often tried first in tonic-clonic seizures

14

Carbamazepine Pharmacokinetics

**Strong inducer of CYP450 enzymes --> self-induction + drug-drug interactions

15

Carbamazepine Adverse Drug Reactions

Diplopia-ataxia-sedation --> dose-related

GI upset

Rare but serious

Aplastic anemia-agranulocytosis --> monitor CBC

Hepatotoxicity --> monitor liver function tests

16

________ and phenobarbital enhance the inhibitory effect of GABA (↑ opening of Cl- channels)

Benzodiazepines

Valproate appears to act partly by this mechanism

17

A drug of choice for partial seizures

Often tried first in tonic-clonic seizures

Carbamazepine

18

Diplopia-ataxia-sedation --> dose-related

GI upset

Rare but serious

Aplastic anemia-agranulocytosis --> monitor CBC
Hepatotoxicity --> monitor liver function tests

Carbamazepine

19

Strong inducer of CYP450 enzymes -->
self-induction + drug-drug interactions

Pharmacokinetics

Carbamazepine

20

Initial therapy IV diazepam (lorazepam or midazolam) until seizures stop or 20 mg given

Then start phenytoin or fosphenytoin slow infusion

If seizures persist IV phenobarbital until seizures stop

If seizures still continue, pentobarbital or propofol infusion with pressor support

Status Epilepticus

21

Neonatal status epilepticus

Adjunct for partial and tonic-clonic seizures

Phenobarbital

22

Metabolized slowly by P450 system - t1/2 of 4-5 days

Classic enzyme inducer

Phenobarbital

23

Irritability - overactivity in many children, sedative effects in others

Mild ataxia, nystagmus, skin rash, osteomalacia

May interfere with learning (cognitive deficits)

Phenobarbital

24

A drug of choice for partial seizures

Often tried first in tonic-clonic seizures

Carbamazepine

25

Decrease in low-threshold Ca++ (T-type) current

Oscillatory currents in thalamic neurons are abnormal in absence seizures - blocked by ethosuximide-valproate

26

Inhibition of high-voltage activated Ca++-channels

VSCC (aka N-type) involved in regulation of glutamate neurotransmitter release - lamotrigine

27

Inhibits function of synaptic vesicle protein SV2A

Impairs Ca++-mediated neurotransmitter release - levetiracetam

28

________ --> block excitation of cells firing repetitively (epileptic foci) leaving low frequency firing neurons (normal) unaffected

Blockade is use-dependent

Phenytoin, carbamazepine, lamotrigine, valproate

29

Inhibition of Sodium Channel Function

Block sustained high-frequency repetitive firing of APs that can initiate seizure formation

Phenytoin, carbamazepine, lamotrigine, valproate

30

Impairs Ca++-mediated neurotransmitter release - levetiracetam

Inhibits function of synaptic vesicle protein SV2A