[PHARM] Pharmacology of Epilepsy [Segars] Flashcards

1
Q

At the most basic level, what is the neuronal imbalance involved in epilepsy?

A

TOO MUCH glutamate, aspartate [excitation]

TOO LITTLE gaba [inhibition]

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2
Q

What are the (4) general MOAs of antiepileptic drugs?

A
  1. Suppress excitatory (glutamate) transmission
  2. Enhance inhibitory (GABA) transmission
  3. Block T-type Ca2+ channels
  4. Novel mechanisms
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3
Q

When are Na channel blockers most effective in exerting their effects?

Why does this make sense?

A

Most effective : Open state and Fast-inactivated state

If the activation gate is open, then the drugs can access the pore of the Na+ channel!

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4
Q

If the Na+ channel activation gate is OPEN… anti epileptic drugs __________

If the Na+ channel activation gate is CLOSED… anti epileptic drugs _________

A

If the Na+ channel activation gate is OPEN… anti epileptic drugs CAN access the pore

If the Na+ channel activation gate is CLOSED… anti epileptic drugs CANNOT access the pore

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5
Q

The probability of Na blockade is proportional to ___________________

A

The probability of Na blockade​ is proportional to the frequency of Nav channel opening and dose

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6
Q

What are the (6) drugs contained in the Na blockers that specifically prolong fast inactivation state?

A

Carbamazepine (oxcarbazepine/eslicarbasepine)

Lamotrigine

Phenytoin

Topiramate

Valproic acid

Lacosamide** (Zonisamide_, Rufin_amide**)

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7
Q

What is the one drug within the Na Blockers that prolong fast inactivation has an additional effect?

What is that effect?

A

Lacosamide

Enhance slow inactivation of Nav channels

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8
Q

What are the (2) AMPA receptor blockers?

A

Topiramate

Perampanel

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9
Q

What is the (1) NMDA receptor blocker?

A

Felbamate

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10
Q

What enzymes break down GABA endogenously?

A

GABA Transaminase : GABA-T

Succinic Semialdehyde Dehydrogenase : SSD

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11
Q

What is responsible for reuptake of GABA in the synaptic cleft?

A

GABA Transporter 1 (GAT-1)

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12
Q

What drugs (2) inhibits GABA-T?

A

Vigabatrin

Valproic acid

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13
Q

What drug inhibits GAT-1?

A

Tiagabine

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14
Q

What drug has dual action by inhibiting GABA-T AND SSD?

A

Valproic acid

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15
Q

GABA promoting agents

What are the (2) categories of pre-synaptic drugs?

A

GAT-1 inhibitor

GABA-T inhibitors

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16
Q

GABA Promoting agents

What is the (1) GAT-1 pre synaptic inhibitor?

A

Tiagabine

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17
Q

GABA promoting agents

What are the (2) GABA-T inhibitors?

A

Vigabatrin

Valproic acid

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18
Q

What are three classes of drugs that will enhance the post synaptic GABAergic neuronal transmisson?

A
  1. Barbiturates
  2. Benzodiazapines
  3. Topiramate
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19
Q

What is the major difference b/w the MOA of benzodiazepines and barbiturates?

A

Benzos are GABA DEPENDENT

Barbiturates are GABA INDEPENDENT

20
Q

What are the (3) MOA of topiramate?

A

GABA(A) agonist = Increases frequency of GABA(A) receptor activation

Increases fast inactivation of Na channels

Acts as an AMPA receptor ANTAGONIST

21
Q

What are the (7) post synaptic GABA promoting agents?

A

(2) Barbiturates : Phenobarbital, Primidone

(4) Benzos : Clonazepam, Clobazam, Lorazepam, Diazepam

1 Rando: Topiramate

22
Q

What are the key MOA to absence seizures?

A

T-type Ca2+ that mediate a 3Hz spike and wave activity in the thalamus

23
Q

What drug class is used to treat ansence seizures?

A

Antagonists of T-type Ca2+ channels

24
Q

What is the ONE drug that is ONLY used for absence seizures?

A

Ethosuximide

25
Q

There are two other drugs that have multiple MOAs that also block the Ca2+ T-type channels. What are they?

A

Valproic acid

Zonisamide

26
Q

What are the (2) synaptic vesicle 2A protein blockers?

A

Levetiracetam

Brivaracetam

27
Q

What (2) drugs inhibit the alpha2delta Ca2+ channel?

A

Gabapentin

Pregabalin

28
Q

What is the BRAND NEW drug that opens K+ channels?

A

Ezogabine

29
Q

What are the (2) drugs with 3 MOAs?

A

Topiramate

Valproic acid

30
Q

What are the (3) MOAs of topiramate?

A

Na+ channel blocker

AMPA receptor blocker

Post synaptic GABA promoting

31
Q

What are the (3) MOA of valproic acid?

A

Na+ channel blockers

GABA-T inhibition [GABA promoting agents]

Ca2+ T-type channel blockers

32
Q

What is a drug OUTSIDE the drug tree that is used for dravet and lennox-gastaut syndrome?

A

Cannabidiol

(Epidiolex)

33
Q

What are the 2 broad warning/risks of ALL antiepileptic medications?

A
  1. Abrupt withdrawal of antiepileptic medication may cause status epilepticus
  2. Suicidal behavior and ideation
34
Q

What is the pharmacokinetic profile of phenytoin?

A

Zero-order

(dose titration upward may exceed Vmax of patient)

35
Q

What is a profound interaction phenytoin has?

A

Inducer of CYP-450

36
Q

What are the two major toxicities of phenytoin?

A

Gingival hyperplasia

Hypocalcemia/vit D deficit/osteoporosis

37
Q

What are the interactions of carbamazepine?

A

Inducer of CYP-450 enzymes

38
Q

What are the toxicities associated with carbamazepine?

A

Leukopenia

Neutropenia

Thrombocytopenia

39
Q

What is the major benefit to using Oxcarbazepine over carbamazepine?

A

It’s an alternative active metabolite that is a less potent CYP450 inducer

40
Q

What is the major toxicity associated with vigabatrin?

A

Permanent vision loss

41
Q

What is the only way a physician can prescribe vigabatrin?

A

REMS program

Risk evaluation and mitigation strategy

*It is vastly important that physicians understand this devestating side effect of permanent vision loss before prescribing

42
Q

What are the major AED interactions with other medications?

A

Contraceptives [decrease efficacy]

Anticoagulants [increase clearance]

Antivirals [increase clearance]

43
Q

What are the newer AEDs attempting to utilize as a clearance method?

A

RENAL clearance

44
Q

What is your first line agent for status epilepticus during INITIAL THERAPY?

First IV?

No IV access?

Second IV?

A

In first IV: Lorazepam, Diazepam

No IV access: Midazolam

In second IV: Fosphenytoin, phenytoin, valproic acid, levetiracetam

45
Q

What are your SECONDARY therapies for status epilepticus?

A

Fosphenytoin

Midazolam

46
Q
A