Lecture 19 - Anti-Epileptic Drugs

Question 1

what is the goal of AED?

Answer 1

Decrease the frequency and/or seizures in people with epilepsy

Not curative

Question 2

considerations for selection of the right AED?

Answer 2

Simplest regiment 
monotherapy better than poly 
Minimize side effects
Cost
Compliance

Question 3

Mechanisms of sz – what is meant by weighted inhibtion ?

Answer 3

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

Question 4

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

Answer 4

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

Question 5

Drugs which target Na Channels?

are they older or new generation?

Answer 5

Phenytoin – older gen

Carbarmezpine – older

Oxcarbazepine – new gen

Lacosamide – New Gen

Esclicarbaepine (Stedesa) – new

Question 6

Phenytoin

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

Answer 6

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

Question 7

Carbamazepine

Mechanism?
use?
Metabolism? Metabolites?
Side effects?

Answer 7

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

Question 8

Oxcarbazepine

mechanism?
special use?

Metabolism?

Answer 8

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

Question 9

Lacosamide

mechanism?

Answer 9

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

Question 10

Esclicarbaepine (Stedesa

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

Answer 10

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

Question 11

Drugs that effect GABA transmission/

what GABA receptor?

Answer 11

GABA a

Benzos
Barbituates

Question 12

Misnomer drugs?

where do they actually work?

Answer 12

PreGabalin and GABApentin

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

Question 13

Benzos

Mechanism?
clinical use?
side effcts

Answer 13

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

Question 14

Barbituates

Mechanism?
clinical use?
side effcts

Answer 14

GABA mimetic and GABA potentiating

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

Clinical use is decreasing

Question 15

PreGabalin and GABApentin

Mechanism?
Clinical use?
side effects?

Answer 15

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

Question 16

rationale for using broad spectrum drugs for Tonic Clonic sz

Answer 16

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

Question 17

Name 5 broad spectrum drugs

Answer 17

Valproate
Lamotrigine 
Zonisamide 
Topmirate 
Levatriacetam

Question 18

Valproate

Pleoitropic mechanism?

who should this drug never be given to?

Answer 18

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

Pregnancy – Teratogenicity;

Question 19

3 drugs that interact with Valproate/

Answer 19

Cabamazepine – -can induce each other’s Metabolism Inhibitors phenobarbitol metabolism –

Displaces Phenytoin from binding proteins – increasing toxicity

Question 20

Lamotrigine

mechansims?
Metabolsim?

Answer 20

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

		Metabolism -- glucouronidse

Question 21

Zonisamide

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

uses?

Answer 21

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

Question 22

Topmirate

mechanisms?
Ineffective for?

Answer 22

Ineffective at Absence sz

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

Question 23

why is felbmate rarely used?

Answer 23

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

Question 24

Levatriacetam (Keppra)

mechansim?

Answer 24

Modulation of the synaptic vesicles

Enhanced docking and release of GABA

Question 25

Channel of interest for Absence sz?

Answer 25

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

Question 26

main drug for absence?

other drugs which also target the reeptor of inteste t

Answer 26

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

Valproates 

Zonisamide --

Question 27

drugs which induce p450 metabolism?

Answer 27

Carbamazepine
Phenyoin
Phenobarbitol
Oxcarbazepine 
Topiramate

Question 28

Drugs which inhibit OCP function?

Drugs which cause renal stones?

Answer 28

Topiramate
Oxcarbazepine

Zonisamide, Topiramate