Epilepsy Drugs

Question 1

What are the four main pillars of epilepsy treatment?

Answer 1

Drugs, Diet, surgery, vagal stimulation

Question 2

Define Anticolvulsant Hypersensitivity syndrome.

Answer 2

Life threatening ADR may occur in the first 1-8 weeks of epilepsy treatment
Fever
Rash
Viceral involvement (often liver)

Question 3

What is the occurrence rate of AHS? what population has the highest risk?

Answer 3

1/1000,1/10,000

Most commonly Han Chinese

Question 4

What class of drugs causes AHS?

Answer 4

Aromatic drugs:

phenobarbital, phenytoin, carbamazepine, lamotrigine

Question 5

Deine refractory/intractable patients. What portion of patients achieve seizure freedom?

Answer 5

2/3 are drug responsive and will never get a seizure

1/3 never achieve drug control –> refractory

Question 6

How do you know if a patient is intractable? refractory?

Answer 6

if they dont respond to an appropriate dose of a drug–> probably intractable
appropriate dose of 2 drugs–> definitely refractory

Question 7

What kinds of seizures are intractable?

Answer 7

Complex partial seizures (also most common in adults)

West’s and Lennox-Gastaut syndromes seizures

Question 8

What are common comorbidities with epilepsy?

Answer 8

depression, anxiety, and suicide risk (3x)

Question 9

What are common side effects with AED? Is abuse an issue?

Answer 9

Sedation, and stomach upsets

compliance is an issue, abuse is NOT

Question 10

Is polypharmacy attempted in epilepsy?

Answer 10

Yes if the seizures are intractable

New compounds with few drug interactions have reawakened interest in rational polypharmacy

Question 11

What is the effect of valproate on other drugs?

Answer 11

It increases blood levels of other drugs

Question 12

What are the effects of phenobarbital, phenytoin, and carbamazepine on blood levels of other drugs?

Answer 12

They decrease blood levels of other drugs

Question 13

What class of drugs affect birth control pills?

Answer 13

Inducer drugs, which are the amine groups drugs: phenobarbital, carbamazepine, phenytoin, and lamotrigine

Question 14

What AED interacts with warfarin?

Answer 14

phenytoin

Question 15

what are blood levels of the drug used for?

Answer 15

determine if concentrations are in therapeutic range, occurrence of ADRs in liver, kidneys or blood
noncompliance

Question 16

How does withdrawal of AED happen?

Answer 16

Withdrawal should never be done quickly
risk for rebound seizures or status epilepticus
risk for losing driver’s license if rebound seizure occurs

Question 17

How does pregnancy affect treatment?

Answer 17

one drug is continued

Risk of seizures on the baby is higher than risks related to treatment

Question 18

What is the teratogenic effect of AED during pregnancy?

Answer 18

Risk of teratogenicity increases with increased number of drugs
Phenytoin and valproate have the highest risk

Question 19

What are the three mechanisms of AED action?

Answer 19

1- inhibition of voltage dependent Na channels
2- enhancing the activity of gaba-a receptor
3- inhibition of T voltage dependent Ca channels

Question 20

What is the function of Na channel and what drugs inhibit it?

Answer 20

initiates action potentials
cycles between active, inactive, and resting states.

phenytoin and carbamazepine hold the channel a little longer in its inactive state–> lengthen the refractory period.

Question 21

What drugs enhance the activity of gaba-a? how does this reduce seizures

Answer 21

barbituates and benzodiazepines

- increase gaba-a mediated Cl influx–> maintaining the membrane near its resting potential and reducing excitability

Question 22

What is the risk associated with gaba-a mediating drugs?

Answer 22

sedation

paradoxical irritability especially in children

Question 23

What drugs inhibit T type voltage gated Ca channels and what type of seizures are they used for?

Answer 23

Ethosuximide

these channels are highly important in the thalamus function–> absence seizures

Question 24

What are rare side effects of ethosuximide?

Answer 24

Photophobia and hiccups

Question 25

What drugs are used only for tonic-clonic and partial seizures?

Answer 25

Phenobarbital Phenytoin carbamazepine levetiracetam

Question 26

What patient population is phenobarbital used in?

Answer 26

Children (Partial seizures and tonic-clonic seizures)

Question 27

What are some side effects of phenytoin?

Answer 27

Gingival heprplasia, hirsutism, acne becomes zero order metabolism at therapeutic levels --> half life becomes larger Nystagmus, ataxia

Question 28

What patient population is phenytoin used in?

Answer 28

It is well tolerate in elderly patients

Question 29

What is the mechanism of action of levetiracetam? and what is the associated risk of drug interaction

Answer 29

Decrease transmitter release (SV 2A binding) | very few drug interactions

Question 30

What drugs are used as broad spectrum drugs to reduce seizures? what kind of seizures do they act on?

Answer 30

Tonic clonic, absence, and partial Valproate, clobazam, lamotrigrine, topiramate.

Question 31

What are the side effects of valproate?

Answer 31

Hairloss, tremor, weight gain, bruising, and bleeding Hepatitis especially in young children highly teratogenic

Question 32

What class of drugs is clobazam? what's the associated risk of using it?

Answer 32

Benzodiazepine --> gaba-a Sedation, personality change dependence after 6 months

Question 33

What is the risk of using lamotrigine?

Answer 33

Some patients show a rash that develops to hypersensitivity syndrome

Question 34

What are the side effects of topiramate?

Answer 34

Sedation | Weight loss

Question 35

What drugs are used IV? what for?

Answer 35

``` Status epilepticus Benzodiazepines (lorzepam, diazepam, midazolam) Phenytoin Propofol, phenobarbital, pentobarbital Full sedation if nothing works ```