AED - Epilepsy Meds Yoyoyo Flashcards Preview

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Flashcards in AED - Epilepsy Meds Yoyoyo Deck (54)
1

What is the goal of Anti-epileptic drugs? 

GOAL: max quality of life by minimizing seizures and adverse drug effects but may not be lifelong treatment 

 

Decrease the frequency and/or severity of seizures 

Treats the symptom of seizure but no the underlying epileptic condition 

[currently, no anti-epileptogenic drugs available] 

2

Factors to consider when selecting AED regimen?

 

Describe the difference between Narrow Spectrum and Broad Spectrum AEDs? 

Seizure type!!!

Monotherapy vs polytherapy

Side Effects!!! 

Patient Adherence 

 

Narrow Spectrum - 1 Mechanism of Action for PArtial Seizures

Broad Spectrum - for all and have more than 1 mechanism of action

3

Name the Broad Spectrum drugs we learned about....Whats the way to remember them eh? 

Valproate

Lamotrigine

Topiramate

Levetiracetam

Zonisamide

[Valery Likes To Lick Zeus}

4

Name the Narrow Spectrum Agents by old and new generation

Old - Carbamazepine, Phenytoin, Phenobarbital

CPP

New - Gabapentin, Oxcarbazepine, PRegabalin, Lacosamide

GLOP

5

What seizures are the Narrow Spectrum drugs (GLOP and CPP) used for? 

Partial Onset that can be simple, complex, or tonic-clonic but with focal/partial onset

6

What is the Treatment for Absence seizures and briefly describe it's mechanism of action? 

Ethosuximide

 

Targets T type Caclcium channels 

7

What is the like most severe way to KO generalized onset seizures? 

Benzodiazepines or barbituates

 

Like hitting with a sledge hammer

very sedating

8

Describe the role of "weighted inhibition" or Inhibitory surround in the brain and what types of neurons are in competition for balance in the pathology of seizures.

Normally, Inhibitory (GABA/Glycine interneurons) outweigh excitatory NT/inputs - hence the term "Weighted Inhibition" and they perform surround inhibition to prevent synchronization of adjacent neurons so you dont get excitatory spread with signaling (excitatory signaling with Glutamate and Aspartate)

 

Seizure generation occurs when you lose GABA input and excitation is weighted more than inhibitory 

- get bursts of EPSPs and Na and Ca currents and burst firing in Paroxysmal Depolarization (generation of seizure) 

9

Describe the cellular mechanisms for Partial and Secondary Generalized seizures and highlight the areas where we use drugs to intervene

Main Mechanism: Depolarizing Shift!!!

see burst of high electrical activity by a column of neurons that's lost inhibitory inputs

Recurrent EPSP --> Ca spikes --> repetive spike

Rapid Neuronal Discharge at Seziure Foci OPENS NA CHANNEL!!

 

Therefore drug-targets are to either BLOCK NA CHANNELS or INCREASE GABA INHIBITIOIN

 

10

What are the Na Channel blockers used as narrow spectrum and how do they work? 

Na Channel Blockers: Phenytoin, Carbamazepine, Oxcarbemazepine, ESL (Stedesa), Lacosamide

 

Prevent prolonged activation but dont block the initial opening of the channel so neurons retain their ability to generate APs at lower frequencies but not get rapid generation like with seizures

 

"Use-Dependent BLockade" = Work only AFTER channel has been opened under normal circumstances and prolons inactivation state and increased refractory period

11

How does Phenytoin work? What is it used for? 

Phenytoin is a Na Channel blocker that is a first-line agent in treatment of partial seizures and should be considered/compared with Carbemazepine and Lamotrigine for risk/benefit

 

First line agent partial seizures

AND

GIVEN IV IN STATUS EPILEPTICUS

12

What are the "TO KNOW" Facts about Phenytoin? 

Name some specific adverse events. 

Phenytoin is 95% bound to plasma albumin, inactivated by metabolism in liver, is a P450 inducer (can induce its own metabolism)

SATURATION KINETICS (linear at low doses zero order at higher doses) so small increase in dose can cause large, unpredictable increase in plasma concentration

 

Adverse Effects:

- Cerebellar effects= Ataxia, Nystagmus, Incoordination

-Cerebral effects = Confusion

-Ugly Effects = Hirsuitism and Facial coarsening and systemic skin rash

The worst - 15-50% get GINGIVAL HYPERPLASIA!

 

13

What kind of drug is Carbemazepine? How does it work? When is it used? 

Carbemazepine is actually a tricyclic antidepressant that here is a Na-Channel blocker used as a first line agent in Partial Seizures (especially good when effects of Phenytoin are too great) 

Occasionally used in Tonic-Clonic 

14

What are the TO KNOW facts about Carbemazepine metabolism and side effects? 

Carbemazepine is inactivated by metabolism in liver and its active metabolite, 10-11 Epoxy Metabolite, may contribute to neurotoxicity

 

It induces its own metabolism and increases rate of metab during first 3-6 weeks so neets to be titrated correctly, large doses may be necessary

 

Side Effects: 

Sedation, Drowsiness

HA

Dizziness

Blurred Vision

15

What is Oxcarbazepine? How does it work? What is it used for? 

Oxcarbazepine is a newer drug closely related to Carbamazapine but with a lower side effect profile and less induction of P450 enzymes in liver metabolism 

Used in kids >4 yo

Used as first-line monotherapy or in add-on therapy for partial seizures 

 

Slows Na channel recover - NA channel blocker 

Also may augment K+ and Ca+ channels to help hyperpolarize cells

16

What are the TO KNOW facts about Oxcarbazepine and its side effects? 

some induction of P450 but much less 

 

LOW side effect profile including simply sedation!

*Watch out for low sodium of on concomitant Diuretics 

 

ORAL CONTRACEPTIVE INTERACTION

17

What is Elsicarbazepine Acetate (ELS/Stedesa)? How does it work? what is it used for?

similar to Carbamazepine/oxcarb by blocking fast-acting GV Na channel but has greater affinity for inactive state (vs resting state) so more selective for rapidly firing neurons!!!! 

 

ELS is a pro-drug and so metabolized into active compound at active site so relatively little side effects 

Used mostly now as add=on therapy for Partial Seizures 

 

No auto-induction of metabolism

18

What are the TO KNOW facts for ESL/Stedesa and Adverse effects?

Decreases ORAL CONTRACEPTIVE AVAILABILITY

 

Favorable drug-drug interaction profile, low protein binding and minimal effect on hepatic cytochrome P450 enzyme 

 

Well-tolerated and most common effects are Dizziness, Somnolence, HA, N/V 

Once Daily Dosing 

19

What is LAcosamide? How does it work/what is it used for? 

 

Side effect? 

Add-on therapy for poorly controlled partial seizures 

Mechanism is unclear but appears to change shape of Na-Channel to slow rate of synaptic transmission 

 

Well-tolerated - dizziness main side effect

20

What are the Benzodiazepines? What are they used for? How do they work? 

Benzodiazepines - Diazepam and Lorazepam 

Enhance effectiveness of GABA-mediated inhibtion and icnrease frequency of Cl channel opening when GABA bound to receptor

 

LAST LINE of choice bc prominent adverse effects and can develop tolerance 

Now used only to ablate seizures acutely and IV infusion for treatment of Status Epilepticus 

21

What are the TO KNOW facts and side effects about Benzodiazepines? 

NOT first line choice - last line because prominent side effects of Sedation, Dizziness, Ataxia, Drowsiness

 

TOLERANCE - can lose effectiveness in as short as 6 months

 

 

22

What are the Barbituates used in Seizures? How do they work and how are they used? 

 

What are the side effects? 

Barbituates = Phenobarbital

GABA-mimetic and GABA-potentiating - can open Cl channel and interact with GABA-A at binding site separate from benzo site 

 

Used in Partial Seizures and Tonic clonic as an alternative drug and used less clinically bc of heavy side effects: 

- HEAVILY sedating

- Cognitive Defects

Tolerance and Withdrawal

23

What are Gabapentin and PRegabalin? How do they work? How are they used? 

Gabapentin (Neurontin) and Pregabalin (Lyrica) are GABA-like compounds that do NOT act at that receptor --> Instead, they acts on Alpha2-Delta1 subunit on VG Ca2+ channels on Excitatory neurons to reduce Ca current and decrease neuron firing and excitatory transmission

 

Used as add-on therapy for PArtial Seizures and Tonic Clonic seizures 

24

What are the TO KNOW about Gabapentin/Pregabalin? 

Both are excreted unchanges into the urine and so do not interfere with the metabolism of other drugs!

 

Approved for children - BERRY FLAVORED LIQUID!

 

Well-tolerated with limited side effects including Somnolence, Dizziness, Ataxia 

Some behavior and learning difficulties reported in kids but less sedating than classic AEDs 

25

What's happening in the phases of Tonic Clonic seizures? 

Tonic Phase - seizure with long train of neuronal firing from acute sudden loss of GABA input

Clonic Phase - Gaba back in alternating fashion and oscilation of currents 

 

Post-Ictal GABA re-maintains inhibitory control 

26

What drugs are used as Broad Spectrum AEDs? just List them! 

Valery Likes To Lick Zeus

Valproate

Lamotrigine

Topiramate

Levetiracetam

Zonisamide

27

What is Valproate? Mechanism of Action and uses? 

Valproate (Valproic Acid aka Depakene) has 3 mechanisms: 

1) Inhibits Low-Threshold T-Type Ca Channels

2) Slows Rate of Na channel Recovery

3) Increases Availability of GABA at synapse

 

Has many uses: 

First line Therapy for Generalized Seizures but also used in Partial and Absent Seizures 

28

What are the notable drug interactions for Valproate? aka What other AEDs would you NOT use Valproate with? 

Valproate and Carbamazepine induce eachothers metabolism so dont used togheter

 

Valproate inhibits Phenobarbitol metabolism - so dont use together

 

Valproate displaces Phenytoin from binding proteins --> increases its concentration in plasma and increases toxicity 

 

Dont use with old  CPP PArtial Seizure Narrow Spectrum meds! 

29

What are the adverse effects of Valproate? 

Problematic Sedation 

Tremor, Hair Loss, WEight gain

Elevated liver enzymes

GI disturbances

 

 

TERATOGENICITY - Autism, Sensory deprivation, Spina bifida 

30

What is Lamotrigine? How does it work? What is it used for? 

Lamotrigine (Lamictal) is a broad spectrum drug used as an add-on or monotherapy in partial and Secondarily Generalized Tonic-Clonic seizures (not primary) 

 

MOA

1) Slows rate of recovery of VG Na channels

2) Inhibits Glutamate Release

3) Potential inhibition of Ca channels 

31

What are the side effects of Lamotrigine? How is it metabolized? 

Lamotrigine is well tolerated and less sedating than other AEDs but can cause severe dermatitis in 1-2% pediatric patients (esp if given too quickly so start slow) 

 

Metabolized by Glucuronidation in the liver 

32

What is Zonisamide? How does it work and how is it used? 

Zonisamide is a broad spectrum anti-convulsant efficacious as adjunctive therapy for all seizure types (including absence) but only FDA approved for Partial onset  

 

MOA: 

1) Blockade of Na channels

2) Reduction in VG T-type Ca Channels (like Ethosuximide) 

3) REduction of glutamate induced synaptic transmission

 

 

33

What is interesting about Zonisamide dosing and what are the side effects of zonisamide? 

Very Long Half Life (1-3 days) so 1x/day dosing

Has Sulphonamide Groups - NOT USED IN PPL WITH ALLERGY TO SULFA DRUGS

 

Side Effects: Causes Kidney stones and Anhydrosis 

34

What are the newer agents that act to inhibit Glutamate Transmission? 

Act on AMPA/NMDA receptors

- Topiramate - highly pleiotropic

- Felbmate

 

Reduce Glutamate Synaptic Transmission

- Levetiracetam 

35

What is Topiramate? Mechanism of Action? Uses?

Topiramate is a broad spectrum agent used to treat Partial, Generalized Tonic-Clonic, Some Myoclonic seizures - NOT for Absence

 

MOA

1) Glutamate receptor antagonism - AMPA rec (maybe Kainate) 

2) GABA potentiation

3) Na and Ca Channel Blockade

4) Carbonic Anhydrase Inhibitor 

36

What are advantages of Topiramate? What else is it good for? 

topiramate has minimal interactions with other drugs (excpet Oral Contraceptives) 

Approved as a Monotherapy AND approved for kids 2yo and up

 

Can cause weight loss (although bad for kdis) 

 

USED AND APPROVED FOR MIGRAINE PREVENTION

37

What are the Side Effects and Bad things about Topiramate? 

Side effects: 

Kidney Stones

Cognitive/Language difficulties

Tingling Pins/Needles 

 

decrease OC therapy 

38

What is Felbamate? How does it work and what is it used for? 

Extremely potent antiepileptic with inhibition of NMDA and AMPA subtypes of Glutamate receptors

 

*restricted for use ONLY in patients with Refractory Epilepsy 

39

What's So bad about Felbamate that it's only used for refractory epilepsy? 

While it lacks sedative effects.....it does cause: 

 

Adverse Behavioral Effects 

Fatal Aplastic Anemia and LIver Failure!!!!!

40

What is Levetiracetam? How does it work? What is it used for? 

Levetiracetam (Keppra) is a broad spectrum AED with Novel mechanism of action where it enhances Synaptic Vesicles (SV2A) release of GABA 

 

MAY PREVENT EPILPTOGENESIS (all others only treat symptoms)

 

Used for Partial and Generalized Seizures

41

What are the Advantages of Levetiracetam that make it so ideal? 

 

What are the side effects? 

Levetiracetam (Keppra) is *EFFECTIVE AT INITIAL DOSE so no need to titrate (great for pts with frequent seizures) 

Dose-Escalation can be fairly rapid

NO KNOWN INTERACTIONS WITH AEDs

 

Side Effects: well-tolerated

some Mood irritability/psychosis seen 

42

What are the different types of Generalized seizures and what do you see with them? 

Absence - Petit Mal with staring, blinking, lip-smacking/hand movements

 

Tonic-Clonic - Gran Mal

 

Myoclonic - brief Jerks

 

Atonic - Drop attack

43

What are the T-Type Ca channels involved in absence seizures? What's happening where in the brain during an Absent Seizure? 

T-Type channel is primary target in Absent Seizure Treatment bc: 

 

Normally, Thalamus relay setup activated during sleep and T-Type burst firing occurs to maintain sleep state and slow sleep waves

BUT when it is active in awake state then awake but EEG looks like characteristic of sleep state

 

T-Type Channels fire while awake and causes you to be absent!

44

What are the drugs that act on T-Type Calcium Channels? 

Drugs reduce activation of T-Type channels in thalamus = Anti-Absence 

 

Ethosuximide

Valproate

Zonisamide

45

What is Ethosuximide? How does it work? when is it used? 

First-line therapy for Absent Seizures - very effective for that!

 

acts specifically on T-Type Channels in thalamus 

46

How does Ethosuximide travel in body? Side Effects? 

zero to low plasma protein binding 

 

LEss sedating than other drugs and low incidence of adverse effects! 

47

What are the enzyme inducing AEDs for hepatic enzyme induction? 

Carbamazepine

Phenytoin

Phenobarbital 

Oxcarbazepine

Topiramate

48

Drugs used for Epilepsy AND for Neuropathic Pain? easy way to rememebr 

Gabapentin/Pregabalin

Carbamazepine/Oxcarbazepine

Lamotrogine

Levetiracetam

Valproate

 

[Valery Got Pain Like Lenny Cravitz Ought-to}

49

AEDs used for Bipolar Disorder? 

Lamotrogine

Carbamazepine

Valproate

50

AED Drugs used for Migraine?

Valproate

Topiramate

Gabapentin

51

2 DRUGS GIVEN FOR STATUS EPILEPTICUS:

 

 

IV Phenytoin

IV Benzodiazepines

52

Drugs with ORal Contraceptive Interactions?

Oxcarbazepine

ELS (acetazolamide) 

Topiramate

 

T.O.E.

53

What is the ONLY AED with eleptogenic potential? What is it's unique mechanism of action? 

Leveitracetam 

 

Helps with veiscle docking of SV2A on GABA neurons to increase releaes of GABA

54

What are the drugs that act on T-Type Ca Channels? 

 

Ethosuximide

Valproic Acid

Zonisamide