14-Pharmacological Aspects Of Epilepsy

Front 1

4 drugs that suppress the recovery from inactivation of the voltage gated Na channel?

Back 1

Pehnytoin
Carbamazepine
Valproic acid
Lamotrigine

Front 2

MOA:
Phenobarbital
Clonazepam
Diazepam
Lorazepam
Gabapentin
Tiagabine
Vigaatrin

Back 2

Enhance GABA synaptic transmission

Front 3

2 drugs that inhibit the T-type Ca channel?

Back 3

Ethosuximide
Valproic acid

Front 4

What types of seizures are ethosuximide and valproic acid good for?

Back 4

Absence seizures, generalized seizures

This is because the T type Ca channel is expressed in the thalamus, and the rhythmic firing between the thalamus and the cortex may cause generalized seizures

Front 5

Drug I would use for:

-simple and complex partial seizures
-tonic-clonic generalized seizures
-Trigeminal neuralgia

Back 5

Carbamazepine

Front 6

Carbamazepine

MOA
Use

Back 6

Na channel inhibitor

partial seizures, tonic-clonic generalized, trigeminal neuralgia

Front 7

Carbamazepine

kinetic feature

Back 7

It induces microsomal enzymes that metabolize it --> plasma half life decreases over time

Front 8

Carbamazepine

Negative effects

What might you give if you want less toxicity

Back 8

Diplopia
Ataxia
Aplastic anemia
Agranulocytosis

Oxcarbazepine is less toxic, but also less potent

Front 9

Phenytoin

MOA
Use

Back 9

Na channel inhibitor

Partial and generalized tonic-clonic seizures

Front 10

Phenytoin

Kinetic properties

Back 10

Poorly absorbed after muscular injection


Non-linear kinetics --> increases in serum concentration fast
in response to small increase in dose

Induces liver metabolic enzymes

Front 11

Phenytoin

Adverse

Back 11

Gingival hyperplasia, hirsutism, rarely Stevens-Johnson syndrome and hepatic failure

Easy to have toxicity due to non-linear kinetics

Front 12

Drug used for generalized myoclonic seizures

What else is it used for?

Back 12

Valproic acid (Na channel inhibitor)

Generalized myoclonic
Simple and complex partial
Tonic-clonic generalized
Absence

Front 13

Valproic acid

kinetic features

Back 13

Metabolized by Cyt P450, but does not induce liver enzymes

Front 14

Valproic acid

Side effects

Back 14

-hepatotoxicity and fatal fuliminant hepatitis (must monitor live function!)
-Spina bifida - watch out in women who may become pregnant

Front 15

Which drug has the greatest teratogenic potential of all antiepileptics

Back 15

Valproic acid

Front 16

Drug used for monotherapy for partial seizures

Back 16

Lamotrigone

Front 17

Lamotrigone

Adverse side effects

Back 17

Dangerous allergic rashes (esp. kids)
Stevens Johnson

Front 18

First line agent for treating febrile seizures in children?

What else is it used for

Back 18

Phenobarbital

Partial and generalized tonic-clonic seizures (second line)

Front 19

Phenobarbital

Kinetics

Back 19

Strong inducer of P450 enzymes

Front 20

Phenobarbital

MOA

Back 20

-allosteric regulation of GABA receptor
-Inhibits Na conductance
-Blocks some Ca channels, possibly some glutamate receptors

Front 21

Drug for treating myoclonic or absence seizures in children

How does it work?

Back 21

Clonazepam

Enhances GABA signaling

Front 22

Clonazepam

Adverse

Back 22

Low toxicity --> drowsiness

Front 23

Two benzodiazepines used in status epilepticus

Back 23

Diazepam
Lorazepam

Front 24

Drug used in patients who are refractory to other treatments for partial seizures, secondarily generalized seizures, and West syndrome

Back 24

Vigabatrin

Front 25

Vigabatrin

MOA

Back 25

Irreversible inhibitor of GABA aminotransferase

blocks vesicular GABA transporter

Front 26

Vigabatrin

Adverse

Back 26

-confusion and psychosis
-Visual field defects (after long term use)

Front 27

What is West Syndrome and how is it treated?

Back 27

rare epilepsy that occurs in infants, result of impaired GABA neurotransmission

Vigabatrin

Front 28

Tiagabine

MOA
Use

Back 28

Inhibitor of GABA uptake

adjunctive treatment for partial seizures

Front 29

Treatment for uncomplicated absence seizures

MOA?

Back 29

Ethosuximide

Reduces the low-threshold T-type Ca current in the thalamus, disrupts 3Hz spike and wave discharges

Front 30

Topiramate

Use
MOA

Back 30

Use: partial and generalized tonic-clonic seizures, Lennox-Gastaut, West Syndrome, migraines

MOA: blocks voltage-gated Na channels and depresses ligand-gated ion channels (glutamate)

Front 31

Topiramate

Adverse effects

Back 31

Visual problems (myopia, glaucoma), urolithiasis

Front 32

Levetiracetam

Use

MOA

Back 32

Use: partial, generalized tonic-clonic, generalized myoclonic seizures

MOA: binds to Synaptic vesicle protein SV2A, unknown effect

Front 33

Drug generally used to treat neuropathic pain

Other uses?

Back 33

Gabapentin


adjunct against partial and generalized tonic-clonic seizures

Front 34

First line drugs of choice for partial and generalized tonic-clonic seizures

What other drugs could you use?

Back 34

carbamazepine
phenytoin

valproic acid
Phenobarbital (second line due to lots of side effects)

Front 35

Treatment for generalized myoclonic seizures

Back 35

Valproic acid

Can also use clonazepam

Front 36

Treatment for uncomplicated absence seizures

Back 36

ehtosuximide

Front 37

Treatment of absence seizures

Back 37

Valproic acid and clonazepam

Front 38

Adult with absence seizures

What do you use first? What has limited effectiveness and why?

Back 38

Valproic acid

Clonazepam works, but causes sedation and development of tolerance

Front 39

If you have absence epilepsy, what drugs should you NOT give

Back 39

carbamazepine
Phenytoin

These exacerbate!

Front 40

What is the protocol to follow after monotherapy with one drug does not work?

Back 40

monotherapy with a different drug, then monotherapy with a different drug

Finally after all these attempts at monotherapy, add more drugs to the cocktail

Front 41

patient has been on medication for 1 year without a seizure. Can you withdraw meds?

Back 41

no, withdraw if seizure free for 2-5 years

Front 42

Patient on epilepsy drugs gets pregnant. How does her treatment change?

What drugs can cause problems?

Back 42

Continue drugs, but monitor for plasma levels

Increased risk of developmental malformations with phenytoin, cabamazepine, and valproic acid

Front 43

How is status epilepticus different from serial seizures?

Back 43

Status eilepticus = seizure activity for >5 minutes or >2 seizures without recovery of consciousness

Serial seizures= recover consciousness between seizures

Front 44

Acute triggers for status epilepticus

Chronic

Back 44

electrolyte abnormalities, renal failure, sepsis, CNS infection, head trauma, stroke, drug overdose

pre-existing epilepsy, chronic use of alcohol, CNS neoplasms

Front 45

Drug therapy for status epilepticus

Back 45

1. Lorazepam (fast onset)
2. If seizures continue, phenytoin
3. Higher dose of phenytoin
4. Check for signs of extreme hyperthermia
If so, complete anaesthesia

If not
5. Phenobarbitol (second line due to CNS depressive activity)