Imported: Neuro Test 1: Schriefer_Antiepilipetic Drugs

Front 1

What is the major drug interaction of benzodiapepines?

Back 1

Potentiation of CNS depressant effects of antipsychotics, tricyclic antidepressants, sedative hypnotics, alcohol

Front 2

Felbamate (Felbatol) – was approved for use in....? What is a stipulation of its use?

Back 2

adults with partial seizures and in children with seizures associated with Lennox-Gastaut Syndrome

can only be gotten for pts who this is the ONLY DRUG THAT WILL WORK...people have to sign a waiver to use it because it causes high incidence of aplastic anemia, and liver failure

Front 3

MOA of Vigabatrin?

side effects?

use?

Back 3

Inhibits GABA degradation (GABA transaminase) and reuptake

Adverse rxns – **vision loss in 30% of pts**. Also headache, somnolence, fatigue, dizziness.
Used as last resort for infantile spasms.

Also for refractory complex partial seizures

Front 4

MOA of Rufinamide (Benzel)?

tox?

use?

Back 4

Action on sodium channels

Adverse rxns – somnolence, vomiting

Used to treat Lennox-Gastaut syndrome

Front 5

lamotrigene use?

MOA?

**

Back 5

Adjunct drugs for partial seizures
approved add-on drug

acts by slowing recovery in Na+ channels, inhibiting voltage gated Ca channels, and perhaps by inhibiting glutamate release

also:probably block L-type calcium channels to some extent

Front 6

gabapentin use?

Back 6

Adjunct drugs for partial seizures
approved add-on drug

act at a subunit of voltage-gated calcium channels to decrease depolarization-induced calcium influx, which decreases release of excitatory neurotransmitters (glutamate).

also:probably block L-type calcium channels to some extent

Front 7

topiramate use?

Back 7

Adjunct drugs for partial seizures; approved add-on drug; treats TREMORS and prevents migraines

mechanism may involve block of sodium channels and AMPA/Kainate receptors. Other possible uses include treatment of tremors and prevention of migraine.

Front 8

Gabapentin use?

Back 8

effective in treatment of neuropathic pain and fibromyalgia

Front 9

pregabalin use?

Back 9

effective in treatment of neuropathic pain and fibromyalgia

Front 10

Side effects of Lamotrigene? what was the use of this again?

Back 10

Most common – weakness, diplopia, ataxia, nausea, irritability, life-threatening rash, Stevens-Johnson syndrome. Also inhibits carbarmazepine metabolism. Increased risk of cleft lip/palate(?)

Adjunct drugs for partial seizures
approved add-on drug

act at a subunit of voltage-gated calcium channels to decrease depolarization-induced calcium influx, which decreases release of excitatory neurotransmitters (glutamate).

Front 11

Common side effects of Topiramate?

Use?

Back 11

Slight increase in incidence of kidney stones

use: treats tremors, prevents migraines

Front 12

important side effect of Tiagabine?

***

Back 12

Off-label use in patients without epilepsy may cause seizures.

use: adjunct therapy for partial seizures (increases GABA activity)

Front 13

Zonisamide should be avoided in what kind of pts?

Back 13

Avoid in patients allergic to sulfonamides

Front 14

What is status epilepticus?

some causes?

Back 14

A state of continuous seizure activity without recovery of consciousness. Generalized tonic-clonic type is life-threatening (10% fatal)

Some causes – sudden withdrawal of CNS depressants or antiepileptic agents, or drug poisoning

Front 15

drug therapy tx for status epilepticus?

Back 15

IV diazepam or lorazepam followed by maintenance therapy of slow IV infusion of phenytoin (fosphenytoin) or phenobarbital

Front 16

What are the Drugs of Choice for a Primary Generalized Tonic-Clonic (Grand Mal)

briefly describe their MOA
**

Back 16

Valproate (Na block, GABA, Decreased calcium release)
Carbamazepine (Na channel inhibitor)
Phenytoin (Na channel inhibitor)

Front 17

What are the Drugs of Choice for Partial Including Secondarily Generalized seizures?

briefly describe their MOA

Back 17

Carbamazepine
Penytoin
Valproate

Front 18

What are the Drugs of Choice for Absence (Petit Mal) seizures?

briefly describe their MOA

Back 18

Ethosuximide (Ca Channel blocker)
Valproate (Na, Ca, GABA)

Front 19

What are the Drugs of Choice for Atypical Absence, Myoclonic, Atonic seizures?

Back 19

Valproate

Front 20

what is always found as a symptom of epilepsy? if epilepsy is untreated what 2 things might this lead to?

Back 20

Abnormal and excessive EEG discharges (always) – if untreated, may lead to anoxic brain damage. Also danger of “excitotoxicity”. (will just keep happening over and over)

Front 21

Consciousness preserved
Localized EEG spikes
Various manifestations of motor or sensory disturbances related to specific cortical area affected

type of seizure?

Back 21

simple partial

Front 22

Disturbed consciousness
Focal EEG spikes originate from temporal lobe
Confused behavior, automatisms, sensory, emotional distortions

type of seizure?

Back 22

Complex partial

Front 23

Spread of epileptic activity to affect both hemispheres
Loss of consciousness
Motor pattern similar to “generalized seizures”

type of seizure?

Back 23

Partial seizures secondarily generalized

will start as a localized partial seizure, then it will become a generalized tonic clonic

Front 24

Brief, abrupt loss of consciousness
With or without clonic motor activity
Generalized 3 per second spike and wave EEG activity

type of seizure?

Back 24

Generalized
Nonconvulsive type

Absence

Front 25

Major convulsion typified by tonic contraction, conic jerking, and a prolonged post-seizure (postictal) depression of CNS activity
Loss of consciousness
Generalized high voltage EEG spikes

type of seizure?

Back 25

Generalized seizures
Convulsive type:

Tonic-clonic (Grand Mal)

Front 26

this is a disease in which you have mental retardation, and a mirage of seizure types (tonic clonic, absence, etc)

Back 26

Lennox-Gastaut Syndrome

Front 27

What is status epilepticus?

Back 27

repeated seizures

one seizure leads to another

medical emergency

Front 28

3 mechanisms of antieplieptic drugs?

Back 28

Limit sustained repetitive firing of neurons by slowing rate of recovery in Na+ - channels

Enhancing GABA-mediated synaptic inhibition

Limit activation of CA++ - channels

Front 29

this drug Prevents seizures without producing general CNS depression, by reducing the rate at which Na channels recover from inactivation, thus slowing firing

Back 29

Phenytoin

Front 30

MOA of phenytoin?

Back 30

reduce rate at which Na+ channels recover from inactivation, thereby slowing firing.

note: Prevent seizures without producing general CNS depression

Front 31

describe how phenytoin is metabolized.

Also, how is 90% of it found in the body? what does this imply?

Back 31

98% metabolized by liver microsomal enzymes; zero order (no matter the dose it can only be cleared at a certain rate) elimination kinetic at therapeutic concentration (1st order at low doses)

90% plasma protein bound--if displaced you will have loads of side effects

Front 32

what effect will Phenytoin have on the CYP system?

Back 32

Induces hepatic drug metabolizing enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4)

Front 33

what is an important tox of Phenytoin assoc with administration of the drug?

Back 33

Acute toxicity after rapid IV administration – cardiovascular collapse and/or CNS depression

note: Fosphenytoin (a soluble pro-drug of phenytoin) decreases, but does not eliminate, this problem.

Front 34

chronic side effect of Phenytoin? (2 key)

Back 34

behavioral changes,
***gingival hyperplasia, peripheral neuropathy,
osteomalacia***
GI-disturbances,
megaloblastic anemia (decreased vitamin B12), hirsutism, depression of serum folate and vitamin K level.

Front 35

What drug class is Phenytoin?

Back 35

D

It can be used if you have no choice, but it is teratogenic

Front 36

what happens with sudden withdrawal of Phenytoin

Back 36

STATUS EPILEPTICUS

causes tons of seizures!!

make sure if you need to change the drug that you SLOWLY take them off phenytoin

Front 37

Chloramphenicol, dicumerol, cimetidine, and sulfonamides have what effect on Phenytoin?

Back 37

Inhibit its metabolism

What were those drugs again? There were 4 of them..yeah slack ass, flip it over for the answer, and if you didn't remember, mark that shit wrong.

Front 38

Acutely, what effect do phenobarbital and ethanol have on phenytoin?

Chronically?

Back 38

compete for the same metabolic sites leading to an INCREASE in plasma phenytoin (inhibit metabolism)

Chronically, phenobarbital is a classic inducer of drug metabolizing enzymes. So chronically, both phenobarbital and ethanol increase metabolism of Phenytoin

Front 39

Dicumerol, salicylates, BZDs have what effect on phenytoin?

Back 39

displace from protein binding sites to increase plasma level

Front 40

what effect does Carbamazepine have on phenytoin

Back 40

enhances phenytoin metabolism, decreasing plasma levels

Front 41

what effect does phenytoin have on OCP? why is this especially important

Back 41

it will decrease their effectiveness (by inducing CYPs)

this is important because it is also a teratogen, so if you get pregnant while on it, you are harming the baby

Front 42

therapeutic use of Phenytoin?

Back 42

Effective for all types of seizures except absence
Tonic-clonic-seizures in adults or older children
Used in status epilepticus
Wound healing

Front 43

MOA of Phenobarbital?

Back 43

Potentiates GABA inhibitory transmission and decreases glutamate excitation

note: can cause sedation, but can be used at low doses so its not a big deal

Front 44

what effect does phenobarbital have on drug metabolizing enzymes?

Back 44

induces drug metabolizing enzymes

Front 45

what 2 pts (think demographics) would you want to avoid phenobarbital in? why?

Back 45

hyperactivity (children)

confusion in elderly patients, decreased cognitive ability

Front 46

what drug can Precipitate acute intermittent porphyria

Back 46

Phenobarbital

penetrate the brain and cause death of neurons

Front 47

what category drug is phenobarbital?

Back 47

Potentially teratogenic (Pregnancy Category D)

Front 48

MOA of Primidone

Back 48

Structurally similar to phenobarbital
Also has similar pharmacology but less potent-Potentiates GABA inhibitory transmission and decreases glutamate excitation

Front 49

Carbamazepine MOA?

Back 49

Anticonvulsant effects resemble phenytoin (slows recovery of voltage-sensitive Na+ channels).

note: Structurally related to tricyclic antidepressants--so it takes a while to start working

Front 50

aplastic anemia, agranulocytosis can be a side effect of what anti-seizure drug?

Back 50

Carbamazepine and ethosuxamide

Front 51

if you are Asian, and you need to go on Carbamazepine, what should you have done? why?

Back 51

FDA recommends genetic testing before starting therapy in patients of Asian descent.

Hypersensitivity reactions (SJS) in Asians with HLA-B* 1502 gene

Front 52

Oxcarbazepine works like Carbamazepine (how was this agian?)...what is different about it?

Back 52

slows recovery of voltage-sensitive Na+ channels (also like phenytoin)

less likely to cause SJS and agranulocytosis

Front 53

Ethosuximide MOA?

Back 53

Increases neuronal refractory period by decreasing conductance in Ca++ channels (T current).

T currents in thalamic neurons important in generation of absence seizures

Front 54

what anti-seizure drug can cause Parkinsonism?

Back 54

Ethosuximide

Front 55

MOA of Valproic acid?

Back 55

acts via several mechanisms. Blocks recovery in Na+ channels, hyperpolarizes cell via an action on K+ channels and perhaps an action on GABA systems (inhibition)

Front 56

Valproic acid is used for what kind of seizures?

Back 56

approved for absence and complex partial seizures in U.S. May also be useful in treatment of grand mal, myoclonic and febrile seizures. Also used in patients who don’t respond to any drug, regardless of seizure type

pretty much all of them!
It is the Amiodarone of seizure drugs

Front 57

biggest potential tox assoc with Valproic Acid?

Back 57

Hepatotoxicity

especially in kids under 2

Front 58

why are Benzodiazepines typically not used for tx of seizures?

MOA

Back 58

tolerance builds up quick

Suppression of seizure spread in the cortex, thalamus, and limbic structures
May facilitate GABA mediated pre- and post-synaptic inhibition

Front 59

A patient is on phenytoin for her seizures and also wants to start oral contraception. What do you tell her?

****

Back 59

**Phenytoin may decrease the effectiveness of oral contraceptives ** KNOW!

– P450 inducers! – One Pharmaceutical Brings About Rapid Liver Metabolism*

Front 60

List the three commonly known general mechanisms of antiepileptic drug action

Back 60

1. inhibit Na+ channels

2. ↑ GABA -synaptic inhibition

3. Inhibit Ca++ Channels

Front 61

here's another fucking chart to memorize...

Back 61

Front 62

Drug treatment of status epilepticus?

Back 62

• IV diazepam or lorazepam (BZDs)

• Followed by maintenance therapy of slow IV infusion of phenytoin or Phenobarbital—no rapid push d/t risk of CV/CNS toxicity risks

Front 63

Which anti-seizure medication causes gingival hyperplasia?

Back 63

Phenytoin