Anti-epileptic drugs

Question 1

When would rare, life-threatening ADRs occur in treatment for epilepsy? and what is this called/

Answer 1

first 1-8 weeks

Anticonvulsant hypersensitivity syndrome (fever, rash, liver involvement)

Question 2

what is AHS?

Answer 2

Anticonvulsant hypersensitivity syndrome
most common in Han Chinese pop
Caused by aromatic amines (Phenobarb, Phenytoin, Carbamaz, Lamotrigine)

Question 3

What proportion of patients will achieve full seizure response

Answer 3

2/3,

1/3 are refractory

Question 4

If a patient fails to respond to TWO appropriate drugs then…

Answer 4

DEFINITELY REFRACTORY - REFER

Question 5

Which are the MOST common intractable seizures

Answer 5

COMPLEX PARTIAL

Question 6

What are some comorbidities?

Answer 6

1. Depression
2. Anxiety
3. Suicide

Question 7

AEDs… do they cure epilepsy?

Answer 7

NO, suppress temporarily

Question 8

Most common ADRs for AEDs?

Answer 8

1. Stomach upsets
2. Sedation
   POOR compliance…

Question 9

with Epilepsy what is the standard for drug treatment?

Answer 9

MONOtherapy - NOT polypharmacy

Question 10

What is the drug interaction for valproIc acid?

Answer 10

INCREASES blood levels of other drugs

Question 11

What is the drug interaction for Phenobarb, Phenytoin, Carb

Answer 11

DECREASE blood levels of other drugs

Question 12

Interaction between Phenytoin and Warfarin…

Answer 12

(Inducers of CYP 450) so warfarin levels LOWER

Question 13

AEDs and OCPs…

Answer 13

Inducers- failed OCP

Question 14

what can blood levels be used for

Answer 14

1. check therapeutic range
2. check for ADRs in liver, kidney, blood fox
3. Check for non-compliance

Question 15

What are the general withdrawal rules for AEDs?

Answer 15

1. Withdraw over months - NOT quickly
2. Rebound seizures, Status epilepticus may occur
3. May lose license

Question 16

Most women maintained on AED (1 only), which two are KNOWN Teratogens?

Answer 16

Phenytoin, Valproate

Question 17

How do Phenytoin and Carbamazepine work?

Answer 17

1. Partially Inhibit voltage-dependent Na channels (phenytoin, Carb), hold inactive state longer, lengthen refractory period
2. Neuron fires at moderate rates, BUT NOT RAPID rates

Question 18

How do the Barbiturates and Benzodiazepines work?

Answer 18

1. Increase activation of GABA-A receptor

2. Enhance Cl- influx, decrease excitability

Question 19

Problems with Barbiturates and Benzodiazepines work?

Answer 19

Sedating

Paradoxical irritatbility - can be serious in children

Question 20

How does Ethosuximide work?

Answer 20

Inhibit T-type voltage-dependent calcium channels
Important in THALAMUS
(absence)

Question 21

Which is the only drug used for Absence seizures?

Answer 21

Ethosuximide
t-type calcium inhibitor
once a day
Rare sidex - Photophobia, Hiccups

Question 22

4 drugs used for tonic-clonic and complex partial seizures

Answer 22

1. Phenobarb (increase GABA-A inhibition, very sedating)
2. Phenytoin (VDSC, gingival hyperplasia, hirsutism, acne, CAN become zero-order and toxic, longer half life)
3. Carbamazepine (VSDC, less sedating)
4. Levetiracetam ( decreased SV2A release)

Question 23

What is the toxic syndrome associated with Phenytoin increased half life and zero order metabolism?

Answer 23

Ataxia, Nystagmus

Question 24

What are the four Broad-spectrum drugs (Tonic-clonic partial and absence treatments)

Answer 24

1. Valproate (side eft tremor, hair loss, weight gain, bruising, bleeding, teratogenic, fear of hepatitis)
2. Clobazam ( enhances gaba A, benzo, sedation, personality change, tolerance after 6 months)
3. Lamotrigine (VDSC, rash/hypersensitivity syndrome)
4. Topiramate (can cause sedation, and weight loss)

Question 25

Which drug is associated with tolerance after 6 months?

Answer 25

CLOBAZAM

Question 26

Which drugs are used ONLY for status epilepticus?

Answer 26

1. IV Benzo (lorazepam, diazepam, midazolam)
2. IV Phenytoin
3. can use propafol, phenobarb, pentobarb