Anti epileptic Drugs

Question 1

Define status epilepticus**

Answer 1

Generalized tonic-clonic seizures w/ ^^^ frequency (recur before patient returns to normal consciousness from the postictal state)
***MEDICAL EMERGENCY W/ HIGH MORTALITY RATE
(HYPOXIC BRAIN DAMAGE)

Question 2

Describe treatment for status epilepticus:
First line–> Refractory–> Secondary Refractory

What is important to remember about secondary refractory treatment?

Answer 2

1st: IV BDZ, then IV Phenytonin/Fosphenytoin
(*Admin. to prevent seizure reoccurrence even if seizure has stopped)
Refractory: ^^^Phentonin, ^^^ BDZ
Secondary Refractory: Barbs or Propofol
*Note: secondary refractory treatment may require respiratory support

Question 3

3 stages of seizure

Answer 3

1. Aura (convulsive + partial seizures only)
2. Itcus (“seizing”)
3. Postictus (hypoglycemic state–not present in absence seizure)

Question 4

What percentage of patients with uncomplicated tonic/clonic seizures can achieve complete seizure control with treatment?

Answer 4

85%

Question 5

What are three important things we generally try to avoid when administering anti-convulsive agents?

Answer 5

Alteration in:

1. Intellect/alertness
2. Physical abilities
3. Reproductive ability due to therapy
   * Patients generally on tx for life

Question 6

What are four important issues with compliance to consider when choosing anti convulsive therapy?

Answer 6

1. Potential effectiveness
2. Adverse problems (i.e. hirsutism in women…)
3. Convenience (daily pill)
4. $$

Question 7

Describe two reasons why serum drug levels are important in anti convulsive therapy:

Answer 7

1. avoid drug toxicity/ ensure proper dosage

3. check patient compliance

Question 8

Phenytoin:
MOA (3)
(means = likely to be tested!)

Answer 8

Inhibits seizure spread + Suppresses epileptic foci

1. Blocks Ca++ influx
2. ^ Cl- influx (GABA tranmission, IPSPs)
3. ^ affinity for inactivated Na+ channels

Question 9

Phenytoin:

Therapeutic Use

Answer 9

**DOC for all seizures EXCEPT absence epilepsy/ atonic seizures

Question 10

Phenytoin:
ROA (2)
Transport/ Metabolism*

Answer 10

• PO; IV for status epilepticus
• 90% protein bound in plasma
• Metabolized in the liver by saturable enzymes: small dose = ^ in plasma & toxicity

Question 11

5 most important phenytoin ADRs:

Answer 11

1. Gingival hyperplasia (20% kiddos)
2. Hirsutism (compliance*)
3. vestibular disturbance: nystagmus, ataxia
4. Allergic rxn: SJS* rash, hematological
5. Cardiotox with ^ IV bolus

Question 12

CI populations for phenytoin therapy

Answer 12

ALL women of childbearing age; teratogenic

Question 13

Which vitamin should be supplemented in patients on phenytoin therapy? Why?

Answer 13

Vitamin K; phenytoin = CYP3A4 inducer

Question 14

**Carbamazepine:
Therapeutic Uses (3)
When should it NOT be used (2)

Answer 14

1. Gen tonic-clonic seizures (2nd line)
2. Complex partial seizures (2nd line)
3. Trigeminal neuraligia (2nd line)

• Not effective for absence seizures
• Makes myoclonic seizures WORSE

Question 15

Which 2 populations should not take Carbamazepine?

Answer 15

Elderly patients (hepatotoxic) 
Patients with myoclonic seizures ** ACTUALLY MAKES THESE WORSE**

Question 16

Describe the unique nature of carbamazepine metabolism

Answer 16

Auto induces its own metabolism via CYP1A2/2C/3A

*Metabolic rate will ^^ within first 4-6 weeks and stabilize within 1mos

Question 17

**Valparoic Acid:
MOA (3)
Which is a target for treatment of absence epilepsy?

Answer 17

1. potentiates GABA
2. blocks Na+/K+ channels
3. inhibits T-type Ca+ channels (**Tx. absence epilepsy)

Question 18

2 Important therapeutic uses for Valparoic acid

Answer 18

1. Absence seizures refractory to ethosuximide (often 1st line)
2. Bipolar disorder

Question 19

How is it valparoic acid absorbed?
Special method of administration?
Which 4 groups is it CI?

Answer 19

-gut
- can give to kiddos as sprinkles!!! (makes it easy to use)
DO NOT give:
1. kiddos younger than 2
2. elderly
(1 + 2 because hepatotoxic)
3. bleeding disorders
4. Preggos: teratogenic

Question 20

Most common ADR associated with valparoic acid

Answer 20

1 alopecia- problem with compliance

Question 21

2 important DD interactions with valproic acid:

Answer 21

1. Lamotrigine (^ conc by inhibiting P450)

2. Phenytoin (Displaces from plasma proteins, decreases elimination)

Question 22

Ethosuximide:
MOA
Therapeutic use

Answer 22

Blocks T type Ca++ channels

Tx: absence seizures only

Question 23

**Lorazepam and other BDZs:
MOA (3)
Most important use

Answer 23

1. Potentiate GABA
2. inhibit VGNa++ channels
3. block Ca++ channels @ sedating doses
   * *IV admin for status epilepticus

Question 24

Gabapentin:
MOA
Therapeutic use (2)
Advantages to use

Answer 24

• ^ GABA release from central neurons
• Tx: Diabetic neuropathy, occasional adjunct anti epileptic (not very effective for this use)
• *Does not change conc. of other anticonvulsants

Question 25

**Which antiepileptic drug has the HIGHEST probability of causing SJS

Answer 25

**Lamotrigine

Question 26

**Lamotrigine: MOA- inhibits what four things?

Answer 26

1. Ca Channels 2. Na Channels 3. Glutamate release 4. aspartate release

Question 27

**Lamotrigine: | Therapeutic use + stipulations*

Answer 27

Used to treat most all seizure disorders in patients >16yo**

Question 28

Topiramate is abroad spectrum anti epileptic. | What two other conditions are treated with Topiramate?

Answer 28

1. migraine | 2. IICH

Question 29

Three important ADRS with Topiramate?

Answer 29

1. **Renal stone formation (Its hard "TO" pee") 2. paresthesia (CA inhibitor) 3. Loss of mental acuity ("TOPI makes you dopey")

Question 30

``` **Levetiracetam (Keppra): Therapeutic use (2) Most important advantage to use; in which population is it highly indicated? ```

Answer 30

Unknown MOA 1. Adjunct therapy for partial seizures; increasingly used for others 2. Migraines * *Not appreciably metabolized in body; great for patients with hepatic insufficiency (Keppra keeps the liver safe)

Question 31

Oxcarbazepine: MOA Therapeutic use ADR

Answer 31

Blocks VG Ca++ channels Tx partial seizures Causes hyponatremia in first 3 mos

Question 32

Pregabalin: | Most Common Therapeutic Use

Answer 32

neuropathic pain (esp. diabetics)

Question 33

Broad Spectrum Antiepileptics (4)

Answer 33

Lamotrigine (>16yo) Levetiracetam (Keppra keeps the liver safe) topiramate ("TOPI makes you dopey") valproate (No child bearing age ladies!)

Question 34

Narrow Spectrum anti epileptics (4)

Answer 34

Carbamazepine- makes myoclonics worse; not absence Oxcarbazepine- partial seizures Phenobarbital- febrile/ status epilepticus Phenytoin- not absence/atonic

Question 35

Drug only for absence seizure (DOC)

Answer 35

Ethosuximide

Question 36

Why should anticonvulsants be avoided in women of child bearing age despite OCP use?

Answer 36

Anticonvulsants alter hepatic metabolism and plasma protein binding of OCPs--this can lead to unplanned preggos + possible birth defects

Question 37

Measures to be taken with female on anticonvulsant therapy in planned preggos? What is the ideal therapy for these patients?

Answer 37

- Best choice: Keep on same drug if possible. Start ladies of this age/in general on safe drug even before desire for pregnancy!!! * Have to stop barbs, phenytoin, and valproate though if they were taken!!! Switch drug GOAL: mono therapy with lowest possible dose to

Question 38

Describe Fetal Hydantoin Syndrome: | Which drug causes this?

Answer 38

Caused by phenytoin: 1. Cleft lip/palate 2. Congenital heart disease 3. slowed growth 4. mental deficiency

Question 39

Describe epilepsy in pregnant patient: does it get better or worse? why? how do we monitor these patients?

Answer 39

Will ^ # seizures during preggos despite medication use 1. ^ drug clearance 2. ^ maternal volume * monitor by ^ frequency of labs

Question 40

What should be avoided in unplanned pregnancy of woman on anticonvulsant therapy (2)

Answer 40

1. DON’T COMPLETELY REMOVE ANTICONVULSANT 2. DON’T SWITCH ANTICONVULSANT IF PREGNANCY WAS UNPLANNED **Risk of meds is safer than altering therapy

Question 41

What happens if a woman with seizure disorder discontinues anti epileptic therapy during preggos?

Answer 41

^ seizure frequency--> anoxic conditions--> birth defects

Question 42

2 non-pharm therapies for epileptic conditions

Answer 42

1. vagal n. stimulation (pulse generator implant ) | 2. surgical removal of epileptic focus

Question 43

What seizures generally lack auras?

Answer 43

1) absence 2) myoclonic 3) seizures in kids, because kids may not recognize them (a true Melissa statement- hahaha)

Question 44

Post ictus state is caused by?

Answer 44

hypoglycemia

Question 45

General mechanisms for seizure drugs: | If you forget MOA, guess these:

Answer 45

decrease Na/ Ca/ glutamate/ aspartate | increase Cl-/ GABA

Question 46

Serious risk assc with all antiepileptics

Answer 46

Steven Johnsons

Question 47

Role of phenobarbital in anticonvulsive therapy:

Answer 47

-IV administration to stop status epilepticus (2nd refractory) -severe febrile seizure (Emergencies, not maintenance)

Question 48

Two treatments for absence seizures:

Answer 48

valproic acid ethosuximide **via T-type Ca+ channels

Question 49

Felbamate treats?

Answer 49

Lennox Gastaut

Question 50

Age group Lennox Gastaut is seen in?

Answer 50

under 4 yoa

Question 51

Infantile spasms: Age of onset % idiopathic

Answer 51

under 6 months | 15% idiopathic; 85% have identifiable cause

Question 52

Drugs that are absolutely pregnancy X/ not good for managing seizures in child bearing age women?

Answer 52

- barbs - phenytoin - valproate

Question 53

Drug that requires vitamin K supplementation?

Answer 53

phenytoin- induces CYP3A4

Question 54

Which seizure drug is safe in hepatic failure patients?

Answer 54

leviteracetam (Keppra) | -no metabolism in the body ("Keppra keeps the liver safe")

Question 55

Drug that causes hyponatremia in the first three months?

Answer 55

oxcarbazepine

Question 56

Drug that auto-induces its own metabolism/ requires dose release during initial 4-6 weeks of treatment?

Answer 56

carbamazepine

Question 57

Drug that is metabolized by saturable enzymes? What is the consequence?

Answer 57

- phenytoin - can go rapidly from therapeutic --> toxic levels * must monitor patient plasma

Question 58

Drug w/ zero order kinetics?

Answer 58

Phenytoin