Anticonvulsants - Bloom Flashcards Preview

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Flashcards in Anticonvulsants - Bloom Deck (30):
1

Describe two general strategies to treat seizures, and three basic mechanisms which they may employ.

Decrease rates of neuronal discharge or suppress its propagation.

This can be accomplished by alteration of membranae function, inhibition of excitatory signaling, or potentiation of inhibitory signaling.

2

Phenytoin is one of the earliest anticonvulsants.

Describe its mechanism of action and indication.

What about its pharmacokinetics?

Mechanism: Use-dependent sodium channel blockade.

Indication: Tonic-clonic seizures as well as partial seizures.

Pharmacokinetics: Highly protein bound and hepatically metabolized (note: CYP inducer!). Follows zero-order kinetics at high levels.

3

Despite being prototypical, phenytoin has fallen out of favor as an anticonvulsant. Describe the side effects that have contributed to this.

CYP inducer; causes many drug interactions.

Many CNS dose-dependent effects such as nausea, sedation, ataxia, nystagmus & diplopia.

Non dose-dependent effects such as gingival hyperplasia, hirsutism, hypersensitivity, and birth defects (cardiac, palatal)

 

4

What is Fosphenytoin?

What is Oxycarbazepine?

Fosphenytoin is a water-soluble phenytoin prodrug for status epilepticus (IV administration).

Oxycarbazepine is a carbamazepine analog with a better side effect profile and less enzyme induction.

5

Carbamazepine

What is its mechanism of action?

Clinical uses?

Carbamazepine

Like phenytoin, causes use-dependent sodium channel blockade.

Drug of choice for partial seizures (NOT absence)

6

Carbamazepine has a number of side effects and problematic pharmacokinetic considerations. What are they?

Dose-related SE: Diplopia, ataxia, GI upset, drowsiness.

Non dose-related SE: Dyscrasias, spina bifida.

Kinetics: Unpredictable absorption profile, plus CYP induction (like phenytoin)

7

Ethosuximide

Mechanism of action & indication?

Kinetics?

Side effects & toxicity?

Ethosuximide

Blocks T-Type calcium channels, for absence seizures.

Not protein bound, yet has long half-life (liver metabolized). Good oral absorption.

GI upset, lethargy.

8

Valproic Acid

Mechanism of action?

Indications?

Valproic Acid

Several; blocks repetitive neuronal firing, blocks T-type calcium currents, and increases GABA.

For absence, tonic-clonic, partial, as well as myoclonic seizures.

9

Valproic Acid

Kinetics?

Side effects?

Valproic Acid

Plasma protein bound, also a CYP inhibitor

Dose-dependent SE: GI upset, weight gain & hair loss.

Non-dose dependent SE: Hepatotoxicity, spina bifida.

10

Felbamate

Mechanism of action?

Indication?

Side effects?

Felbamate

NMDA antagonist, also potentiates GABA.

Partial seizures, last-choice.

Aplastic anemia and hepatotoxicity.

11

Gabapentin

Mechanism of action?

Indication?

Kinetics?

Gabapentin

GABA analog (yet not an agonist; role unclear)

Partial & tonic-clonic seizures, as well as neuropathic pain and ALS.

No protein binding and no liver metabolism (excreted unchanged)

12

Pregabalin

Mechanism of action?

Indication?

Side effects?

Pregabalin

GABA analog (like gabapentin), also blocks calcium currents.

Partial seizure, neuropathic pain (from several sources)

Very limited abuse potential.

13

Lamotrigine

Mechanism of action?

Indication?

Side effects?

Lamotrigine

Blocks repetitive action potential (Na?)

Tonic-clonic/absence seizures, also bipolar disorder.

Can cause rash (Stevens-Johnson syndrome!)

14

Topiramate

Mechanism of action?

Indication?

Side effects?

Topiramate

Antagonizes kainate/AMPA glutamate receptors, may block use-dependent sodium currents.

Partial seizures (adjunctive), migraine prophylaxis.

Fatigue, nausea, confusion, weight loss (marketed!)

 

15

Tiagabine

Mechanism of action?

Indication?

Side effects?

Tiagabine

Inhibits GAT-1 transporter (increases synaptic GABA)

Complex and partial seizures (adjunctive)

Dizziness, tremor, somnolence.

16

Levetriacetam

Mechanism of action?

Indication?

Side effects?

Levetriacetam

Unknown!

Partial, myoclonic, and tonic-clonic (adjunctive)

Dizziness, asthenia, somnolence.

17

Zonisamide

Mechanism of action?

Indication?

Side effects?

Zonisamide

Blocks sodium and calcium currents.

Partial seizures (adjunctive)

Ataxia, anorexia, nervousness, fatigue, speech impairment

18

Vigabatrin

Mechanism of action?

Indication?

Side effects?

Vigabatrin

Irreversibly inhibits GABA metabolism.

Complex partial seizures & infantile spasms (adjunctive)

Possible pemanent effects on vision.

19

Clobazam

Mechanism of action?

Indication?

Clobazam

Blocks sodium and calcium currents, as well as carbonic anhydrase.

Lennox gastaut epilepsy.

20

Lacosamide

Mechanism of action?

Indication?

Lacosamide

Enhances slow inactivation phase of sodium channels.

Partial seizures (adjunctive)

21

Perampanel

Mechanism of action?

Indication?

Kinetics?

Perampanel

AMPA antagonist.

Seizures, unclear which.

Interacts with CYP inducers...

22

Ezogabine

Mechanism of action?

Indication?

Side effects?

Ezogabine

Potassium channel facilitator (hyperpolarizing)

Partial seizures (adjunctive)

Retinal, vision, and skin abnormalities (permanent?)

23

Rufinamide

Mechanism of action?

Indication?

Rufinamide

Prolongs inactive phase of sodium channels.

Lennox-gastaut epilepsy.

24

Recap

Name four anticonvulsants that affect CYP activity.

Phenytoin, carbamazepine, oxycarbazepine all induce CYPs.

Valproic acid inhibits CYPs.

25

Recap

Name 3 anticonvulsants specifically indicated for absence seizures.

Ethosuximide, Lamotrigine, Valproic acid

26

What is the functional difference between NMDA and AMPA blockade?

Name some drugs that do each of these functions.

AMPA blockade appears to prevent aberrant discharge, while NMDA blockade merely shortens it.

NMDA blockers: Felbamate

AMPA blockers: Topiramate, Perampanel

27

Recap

Name two drugs that are indicated for Lennox-Gastaut epilepsy.

Clobazam, Rufinamide.

28

Recap

What anticonvulsant is also indicated for migraine?

Which are also indicated for neuropathic pain?

Recap

Topiramate

Gabapentin, Pregabalin

29

Recap

Name 2 drugs that are known to affect visual function.

Recap

Vigabatrin, Ezogabine.

30

Recap

What drug is known to cause aplastic anemia?

Which is a D-fructose analog?

Which irreversibly inhibits GABA metabolism?

Which reduces GABA uptake?

Recap

Felbamate

Topiramate

Vigabatrin

Many, but notably Tiagabine.