Lecture 19 - Anti-Epileptic Drugs Flashcards Preview

PT2 B1 > Lecture 19 - Anti-Epileptic Drugs > Flashcards

Flashcards in Lecture 19 - Anti-Epileptic Drugs Deck (28):
1

what is the goal of AED?

Decrease the frequency and/or seizures in people with epilepsy

Not curative

2

considerations for selection of the right AED?

Simplest regiment
monotherapy better than poly
Minimize side effects
Cost
Compliance

3

Mechanisms of sz -- what is meant by weighted inhibtion ?

GABA interneurons inhibitng the surrounding neurons of an excitatory pathway; leading to high fidelity of the excitatory pathway

4

Primary mechanism (Channel) targetted for treatment of partial/secondary generlized sz?

Inactivation of an aberrantly activated Na Channel (Na channel which has lost refractory period)

5

Drugs which target Na Channels?

are they older or new generation?

Phenytoin -- older gen

Carbarmezpine -- older


Oxcarbazepine -- new gen

Lacosamide -- New Gen

Esclicarbaepine (Stedesa) -- new

6

Phenytoin

Primary use?
Mechanism?
Pharmacology?
Metabolism?
Adverse effects?

Very effective and acts quickly -- good for status epilepticus (not first line for Partial)

Mechanism -- Na channel

Bound to albumin

Metabolism -- p450; induces own metabolism; saturaiton kinetics at higher doses; can lead to toxicity

ataxia, nystagmus, incoordiatnion, confusion, hirsutism,
Gingival Hyperplasia

7

Carbamazepine

Mechanism?
use?
Metabolism? Metabolites?
Side effects?

First line for partial seizures, some use in tonic clonic

Suppresses the foci and the spread

Metabolism -- inactivated by liver
Metabolites -- 10-11 epoxy -- neurotoxic

Side effects -- Sedation, drowsiness, HA, dizziness, blurred vision

8

Oxcarbazepine

mechanism?
special use?

Metabolism?


Approved for children
Mechanism: Slow rate of Na Channel recovery
ALSO -- agument K+ channels and block Ca2+ channels


Metabolism by the Liver -- some induction of p450s

9

Lacosamide

mechanism?

Unclear; changes the protein conformation of the Na channel and slows the rate of transmission

10

Esclicarbaepine (Stedesa

whats special about this drug?
metabolism?
dosing?
who should avoid it?

Pro-drug
No autoinduction
Decreases Oral Contraceptive availability
Once daily dosing

11

Drugs that effect GABA transmission/

what GABA receptor?

GABA a

Benzos
Barbituates

12

Misnomer drugs?
where do they actually work?

PreGabalin and GABApentin

Alpha 2 Delta 1 subunit of VG Calcium channel of excitatory neurons; Reduce the excitatory transmission (Glutamate)

13

Benzos

Mechanism?
clinical use?
side effcts

Keep the Channel open, but GABA has to be present to bind

Uses: Last line of choice; "sledge hammer"
Used to ablate seizures such as SE in acute setting


Sedation, dizziness, ataxia, drowsiness, and TOLERANCE

14

Barbituates

Mechanism?
clinical use?
side effcts

GABA mimetic and GABA potentiating


Side effects: heavy Sedation, cognitive effects, tolerance and withdrawal


Clinical use is decreasing

15

PreGabalin and GABApentin

Mechanism?
Clinical use?
side effects?

Mechanism -- Alpha 2 Delta 1 subunit of VG Calcium channel of excitatory neurons; Reduce the excitatory transmission (Glutamate)

Clinical Use: add on therapies for tonic clinic and partial


Approved for children,

side effects -- limited

16

rationale for using broad spectrum drugs for Tonic Clonic sz

Tonic Clonic Seizures --

Tonic phase: Acute and sudden loss of GABA
Clonic phase -- GABA is restore but in alternating fashion

Drugs: Broader specturm drugs --
Drugs with more mechanisms of action

17

Name 5 broad spectrum drugs

Valproate
Lamotrigine
Zonisamide
Topmirate
Levatriacetam

18

Valproate

Pleoitropic mechanism?

who should this drug never be given to?

Inhibits T Type Calcium Channel Slows rate of recovery for Na Channels
Increases GABA availability at the synapse (synthesis)



Pregnancy -- Teratogenicity;

19

3 drugs that interact with Valproate/

Cabamazepine -- -can induce each other's Metabolism Inhibitors phenobarbitol metabolism --

Displaces Phenytoin from binding proteins -- increasing toxicity

20

Lamotrigine

mechansims?
Metabolsim?

Slow rate of recovery of VG Na Channels; Inhibition of glutamate release; Inhibition of Ca 2+ channels;

Metabolism -- glucouronidse

21

Zonisamide

who should not take this drug?
mechanism?
whats good about its regimen?

uses?

Pleiotropic Mechanisms: Na Chnanles, T Type Calcium Channels, Reduction of Glutamate transmission

Absence sz -- T type Calcium channel

Once daily dosing (long half life)

Contraindicated in Sulpha Allergic patients

22

Topmirate

mechanisms?
Ineffective for?

Ineffective at Absence sz

Antagonist at Glu Recetpors
GABA potentiaion
Na and Ca blockers
Carbonic anhydrase inhibitor -- effecting pH

23

why is felbmate rarely used?

cognitive function
Blocks Glutamate Receptors -- behvaioral effects
Liver failure
Aplastic Anemia

24

Levatriacetam (Keppra)

mechansim?

Modulation of the synaptic vesicles
Enhanced docking and release of GABA

25

Channel of interest for Absence sz?

T type Calcium channel active in the Wake state (should normally only be active during sleep)

26

main drug for absence?

other drugs which also target the reeptor of inteste t

Ethosuximide
First line therapy for Absence
High specific -- only going to act on low


Valproates


Zonisamide --

27

drugs which induce p450 metabolism?

Carbamazepine
Phenyoin
Phenobarbitol
Oxcarbazepine
Topiramate

28

Drugs which inhibit OCP function?


Drugs which cause renal stones?

Topiramate
Oxcarbazepine


Zonisamide, Topiramate