Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CNS Drugs > L9 Anticonvulsants > Flashcards

L9 Anticonvulsants Flashcards

1
Q

What is a seizure?

Where do they generally originate?

A

Seizures are abnormal discharges of electrical activity if cerebral neurons.

Generally originate in the cerebral cortex.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is a partial seizure?

What are the 3 types of partial seizures?

A

Partial seizures begin focally in a cortical site and may spread

  1. Simple partial: jerking, lasting 20 seconds, preservation of consciousness
  2. Complex partial: impairment of consciousness < 2 min, automatic movements, originate in temporal lobe
  3. Partial with secondary generalized tonic-clonic: originates as partial and develops into tonic-clonic, loss of consciousness, muscle contractions alternating with relaxation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is a generalized seizure?

What are the 3 types of generalized seizures?

A

Involves both hemispheres from the outset

  1. Tonic-clonic (grand mal): loss of consciousness, muscle contractions
  2. Absence (petit mal): staring, cease activity, <30 secs
  3. Myoclonic: brief shock-like muscle contraction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the main mechanism behind seizure generation?

What is the mechanism behind a partial seizure vs. an absence seizure?

A

Seizures are thought to be a result of under-activity of GABAergic neurons or over-activity of glutamate transmission.

Partial seizure: neurons fire at a very high frequency. Inhibited by drugs which reduce the ability of Na+ channels to recover from inactivation after an action potential to decrease rapid firing.

Absence seizure: characterized by generalized spike-and-wave discharges at 3Hz, orginating from the thalamus. Due to the T-type Ca++ voltage gated channel. Inhibited by drugs that block this channel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which drugs block prolong the inactivation of the voltage-gated Na+ channel and decrease release of glutamate?

A

Phenytoin, carbamazepine, lamotrigine, valproic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Which drugs block the thalamic low threshold T-type Ca++ current?

What type of seizure would this treat?

A

Ethosuximide and Valproic acid

Treats absence seizures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What drugs enhance GABA activity and increase hyperpolarization of neurons by opening Cl- channels?

A

Phenobarbital and benzos

The increase in inhibitory GABA activity protects against generalized and partial seizures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How successful is seizure treatment? What are some general treatment principles with the anticonvulsants?

What are the main side effects of the antiseizure medications?

A

Treatment is completely successful in about 50% of patients. Best to initiate therapy with single drug and switch if it is not effective. Combining drugs is more likely to cause complications.

Monitoring plasma drug levels is frequently done to optimize dosage

Side effects: CNS sedation, hepatic damage, aplastic anemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which of the antiseizure drugs induce cytochrome p450?

A

phenytoin, carbamazepine, phenobarbital

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Phenytoin

A

Block sustained high-frequency repetitive firing of neurons by prolonging inactivation of the Na+ channel.

Effective in partial seizures and generalized tonic-clonic.

No CNS depression, not very sedating

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are some significant pharmacokinetic properties of phenytoin?

A

Fosphenytoin is the water-soluble prodrug that can be used parenterally

Highly (90%) plasma protein bound

Narrow therapeutic range

Metabolism saturated at therapeutic concentrations, so addition of other drugs metabolized by same enzymes may inhibit phenytoin metabolism significantly, increasing concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What drug does phenytoin inhibit the metabolsm of?

A

Warfarin concentration goes way up if combined with phenytoin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What drug increases the metabolis of phenytoin?

A

Carbamazepine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are signs of phenytoin toxicity?

A

Nystagmus

Ataxia and double vision

Sedation at high levels

Gingival hyperplasia and hirsuitism

Coarsening of facial features, mild peripheral neuropathy

Abnormal Vit D metaboism and inhibition of Ca++ absorption leads to osteomalacia

Skin rash-discontinue

Pregnancy category D

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Carbamazepine

A

Blocks Na+ channels, decreases neurotransmitter release

Mood stabilizer: effective in bipolar

DOC: partial seizures, widely used for tonic-clonic as well

Effective at high doses for trigeminal neuralgia

Not very sedating normally

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Carbamazepine increases the metabolism of…

A

phentoin, valproic acid, ethosuximide, clonazepam, haloperidol, oral contraceptives, primidone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

These drugs increase the metabolism of carbamazepine.

A

Phenobarbital, phenytoin, valproic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

These drugs inhibit the metabolism of carbamazepine

A

Cimetidine, fluoxetine, isoniazid, erythromycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the big worrisome side effect of carbamazepine?

What are some other signs of toxicity?

A

Steven Johnson Syndrome: dangerous and potentially fatal necrolysis skin reaction

More common with HLA-B 1502 allele: most common in asian ancestry

Other signs of toxicity: double vision, ataxia, GI upset, drowsiness at high doses, idosyncratic blood dyscrasias (most commom in elderly treated for trigeminal neuralgia)

Pregnancy category D-not used

20
Q

Topiramate

A

Blocks voltage dependent Na+ channels, enhances GABAa currents and limits glutamate receptor activation

Can be effective against ALL types of seizures

Used for West’s syndrome and Lennox-Gestaut syndrome

Used for biopolar and binge eating disorder

Migraine prophylaxsis

Excreted unchanged in the urine 20-30 hr half-life

21
Q

What are the unique side effects of Topiramate?

A

acute myopia and glaucoma-stop drug immediately

Cognitive impairment, nervousness, confusion

Dizziness, fatigue, sedation, paresthesias

22
Q

Lamotrigine (Lamictal)

A

inactivates voltage dependent Na+ channels

May also act on N and P/Q type Ca++ channels as works in absence seizures

Decreases glutamate release

Used in partial seizures, myoclonic and absence in children

Used in bipolar

23
Q

What are the signs of Lamotrigine toxicity?

A

Dizziness, headache, double vision

Nausea, somnolence

Skin rash-discontinue

Dermatitis can be life-threatening in children

Pregnancy category C

24
Q

Phenobarbital and Primidone

A

Prolongs opening of Cl- channel at GABAa receptor

Used for partial and generalized tonic-clonic seizures

Causes drowsiness and CNS depression

Contraindicated in porphyria

Do not use in pregnancy

25
Q

Gabapentin and Pregabalin

A

GABA analogs, does not act on GABA receptors, may augment GABA release

Blocks N-type Ca++ channels, inhibiting glutamate release

Adjunct tx. for partial and tonic-clonic

Widely used for neuropathic pain

Pregabalin-used for fibromyalgia

High doses for antiseizure, lower doses for pain

Excreted by kidney-few drug interactions

Short half-lives

26
Q

Levetiracetam (Keppra)

A

Binds to synaptic vesicular protein (SV2A): reduces glutamate release, increases GABA release

Used for tx of partial, myoclonic, and tonic-clonic seizures

Minimal drug interactions-not metabolized by cytochrome p450

27
Q

Tiagabine (Gabatril)

A

Inhibits uptake of GABA, prolonging inhibitory action of GABA and potentiating tonic inhibition in the brain

Used in adjunct tx of partial seizures

Highly protein bound

28
Q

Vigabatrin (Sabril)

A

Irreversible inhibitor of GABA transaminase, which breaks down GABA in synaptic cleft

Increases GABA levels and tonic inhibition in brain

Approved for refractory adult complex partial seizures and for infantile spasm

30-40% of patients experience irreversible constriction of visual field and/or retinal damage

Pre-existing mental illness is contraindication-agitation and confusion may occur

29
Q

Ethosuximide (Zarontin)

A

DOC for absence seizures

Blocks T-type Ca++ channels: which are part of pacemaker current that generates rhythmic cortical discharge in thalamic neurons thought to cause absence seizures

Given twice per day to decrease GI side effects

30
Q

What is the one significant drug interaction of Ethosuximide?

A

Valproic acic decreases its clearance

31
Q

Valproic Acid

A

DOC if both absence and tonic-clonic seizures occur

First line of tx in bipolar disorder with mixed episodes and rapid cycling

Blocks Na+ channels and high-frequency repetitive firing

Decreases NMDA stimulation

Increases synthesis of GABA

Also useful in myoclonic, atonic, and partial seizures

Severe toxicity possible-still widely used drug

32
Q

What are the significant drug interactions of Valproic acid?

A

Inhibits own metabolism at low doses

Phenytoin (displaces from plasma proteins and increases concentration)

Inhibits metabolism of phenytoin, carbamazepine, lamotrigine, and phenobarbital

33
Q

What are effects of Valproic acid toxicity?

A

Most common: nausea, vomiting, abdominal pain, heartburn

Fine tremor, weight gain, increased appetite, hair loss

Hepatotoxicity: worse under 2 or taking other meds

Contraindicated in liver disease- > 50 deaths in US due to liver damage

Black box warning for pancreatitis

Do not use in pregnancy-birth defects

34
Q

Clonazepam

A

Benzo-used in absence seizures

Effective for myoclonic and infantile seizures as well

Sedation is common

Pregnancy category D

35
Q

Diazepam (Valium) and Lorazepam (Ativan)

A

DOC: status epilepticus, administer IV

Status epilepticus causes death in 20% patients

Should not be given in pregnancy except if absolutely necessary

36
Q

What is Stevens-Johnson Syndrome?

A

Hypersensitivity reaction consisting of erythema multiforme, arthritis, nephritis, CNS abnormalities, and myocarditis

Discontinue use!

Rare

37
Q

What drugs are most likely to cause Stevens-Johnson syndrome?

A

Phenytoin, fosphenytoin

Phenobarbital, primodine

Lamotrigine

Ethosuximide

Valproic acid

38
Q

What anticonvulsants should be avoided in pregancy, but are category C and may be used if necessary?

A

Lamotrigine

Gabapentin

Topiramate

Tiagabine

39
Q

If you are worried about suicide with anticonvulsants, which two drugs would you want to give?

A

Carbamazepine and Valproate

No data for phenytoin

40
Q

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

A

Phenytoin

Carbamazepine

Gabapentin

Levetiracetam

Lamotrigine

Topiramate

Tiagabine

Phenobarbital

Valproic acid

41
Q

What drugs are used for absence seizures?

A

Ethosuximide

Valproic acid

Clonazepam

42
Q

What drugs are used for myoclonic seizures?

A

Levetiracetam

Valproic acid

43
Q

What drugs are used for atonic seizures?

A

Valproic acid

Lamotrigine

44
Q

What drugs are used in infantile spasms?

A

Corticosteroids

Topiramate

Clonazepam

45
Q

What drugs are used in Status Epilepticus?

A

Diazepam or lorazapem iv: most effective

Phenytoin iv

Phenobarbital iv

CNS Drugs (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions