Drug therapy of epilepsy

Question 1

Simple partial seizure

Answer 1

focal, 20-60 sec, consciousness preserved

Question 2

Complex partial seizure

Answer 2

focal, 30-120 sec, impaired consciousness

Question 3

Partial seizures can become _____ and include tonic-clonic activity

Answer 3

secondarily generalized

Question 4

Absence seizure

Answer 4

generalized, < 30 sec; loss of awareness, staring, unresponsiveness

Question 5

Myoclonic seizure

Answer 5

generalized, ~ 1 sec single or multiple muscle spasms

Question 6

Tonic-clonic seizure

Answer 6

generalized, 1-3 min; loss of consciousness, muscle rigidity followed by alternating periods of contraction and relaxation

Question 7

Status epilepticus

Answer 7

continuous generalized convulsive activity

Question 8

List four general strategies to inhibit neuronal activity in seizures

Answer 8

1. Inhibit Na+ channels
2. Inhibit Ca++ channels
3. Potentiate the inhibitory effect of GABA ( Positive modulators of GABAA receptors, GABA uptake inhibitors, GABA-T inhibitors)
4. Inhibit the excitatory effect of glutamate (NMDA receptor antagonists, AMPA/KA receptor antagonists)

Question 9

All antiseizure drugs come with a black box warning for ______ regardless of indication

Answer 9

suicidal ideation

Question 10

_______ is a barbiturate commonly used to treat epilepsy; _______ is a barbiturate used for rapid induction of anesthesia

Answer 10

Phenobarbital

Thiopental

Question 11

Unlike benzodiazepines, barbiturates can produce ______ and depress ____

Answer 11

surgical anesthesia, depress respiratory rate and rhythm

Question 12

Barbiturates are classic CYP ____

Answer 12

inducers- leads to tolerance, drug interactions

Question 13

List common adverse reactions to barbiturates

Answer 13

Depress REM sleep
Rebound insomnia, anxiety, seizures
Paradoxical excitement in children and elderly patients
Can worsen pain perception- not to be used for analgesia
Allergic skin reactions
Pregnancy Risk D
Blood dyscrasias

Question 14

Phenobarbital is generally effective in all seizures except ____

Answer 14

absence

Question 15

Describe the mechanism of action of phenobarbital

Answer 15

Main site of action is the GABAA receptor; increases the duration of GABA-induced Cl- channel openings; inhibits the spread of seizure activity and ↑ the threshold for stimulation of the motor cortex

Question 16

List side effects of phenobarbital

Answer 16

CNS, pulmonary depression, bronchospasm, rash/ derm

Question 17

Phenytoin is used for what kinds of seizures?

Answer 17

prophylaxis of complex partial seizures and generalized tonic-clonic seizures

Question 18

______ is a prodrug of phenytoin used IM/ IV for _______

Answer 18

Fosphenytoin, for status epilepticus

Question 19

Describe the mechanism of action of phenytoin

Answer 19

Main effect is preferential binding to the inactivated state of voltage-activated Na+ channels (use-dependent block); inhibits sustained repetitive neuronal firing
Also decreases the release of glutamate and enhances release of GABA through actions at other ion channels (T-type Ca++ channels, K+ channels)

Question 20

Phenytoin has NO effect on _________

Answer 20

seizure threshold

Question 21

Because of variable hepatic metabolism, ______ is one of few drugs for which metabolic capacity can be saturated within therapeutic concentrations leading to ________ kinetics

Answer 21

Phenytoin

zero order

Question 22

Gingival hyperplasia is a side effect that is somewhat unique to _______

Answer 22

Phenytoin

Question 23

_______ is a drug used for partial seizures and tonic clonic seizures that is preferred over phenobarbital in children because it has fewer behavioral/ alertness side effects

Answer 23

Carbamazepine

Question 24

Describe the mechanism of action of carbamazepine

Answer 24

use-dependent block of voltage-activated Na+ channels; inhibits sustained repetitive neuronal firing

Question 25

Carbamazepine has some adverse reactions that are not seen with other anti-epilepsy drugs:

Answer 25

``` CV changes (also does have CNS, heme, GI, derm side effects common to anti-epilepsy drugs) ```

Question 26

Metabolism of _______ can be affected by the HLA-B*1502 allele, which is common in _____ populations

Answer 26

carbamazepine | South Asian

Question 27

Describe the mechanism of action of valproic acid

Answer 27

Several sites of action: 1) prolongs Na+ channel inactivation, 2) inhibits T-type Ca++ channels in thalamic relay neurons, 3) increases brain concentrations of GABA by a) stimulating glutamate decarboxylase (converts glutamate to GABA) and b) inhibiting enzymes (GABA-T, SSA-DH) that metabolize GABA

Question 28

_______ is effective for all types of seizures and is also used in acute mania, bipolar disorder, migraine prophylaxis

Answer 28

Valproic acid

Question 29

Valproic acid ______ CYPs and UGT

Answer 29

inhibits | other drugs are CYP inducers

Question 30

The DOC for absence seizures is ______ but this drug should not be used as monotherapy for mixed epilepsy because ______________

Answer 30

ethosuximide | increases frequency of tonic-clonic seizures

Question 31

_______ and ________ are GABA analogs that do not bind to GABA receptors but do increase brain GABA concentration

Answer 31

Gabapentin, pregabalin

Question 32

List uses of gabapentin

Answer 32

adjunctive therapy for partial seizures TX of painful neuropathies monotherapy for refractory partial seizures, TX of spasticity in MS, and TX of tremor

Question 33

Describe the mechanism of action of gabapentin (and pregabalin)

Answer 33

Binds N-type Ca++ channels, decreasing Ca++ entry during action potentials, and resulting in decreased synaptic release of neurotransmitters, including glutamate

Question 34

List adverse reactions to gabapentin

Answer 34

drowsiness, dizziness, ataxia, fatigue, nystagmus, tremor, xerostomia, gingivitis, gingival hemorrhage, dyspepsia, constipation

Question 35

List adverse reactions to pregabalin

Answer 35

dizziness, somnolence, ataxia, xerostomia, peripheral edema

Question 36

List precautions for treatment with pregabalin

Answer 36

taper to DC adjust dose for renal insufficiency angioedema

Question 37

Describe treatment options for partial and tonic-clonic seizures

Answer 37

DOC: valproic acid, carbamazepine, phenytoin Alternates: phenobarbital, lamotrigine, topiramate Adjuncts: gabapentin, pregabalin, vigabatrin, tiagabine, zonisamide

Question 38

Describe treatment options for absence seizures

Answer 38

DOC: ethosuximide, valproic acid Alternates: clonazepam

Question 39

Describe treatment options for myoclonic seizures

Answer 39

DOC: valproic acid Alternates: clonazepam, lamotrigine Adjuncts: felbamate

Question 40

Describe treatment options for status epilepticus

Answer 40

DOC: IV lorazepam, IV diazepam, IV fosphenytoin Alternates: phenobarbital, general anesthetics