Brainscape's Knowledge GenomeTM

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


See full index

Pharmacology (Dustin, Ben) > B10-11: Antiepileptics (Broad Spectrum and Non-Broad Spectrum. Drugs for Status Epilepticus) > Flashcards

B10-11: Antiepileptics (Broad Spectrum and Non-Broad Spectrum. Drugs for Status Epilepticus) Flashcards

1
Q

What is the definition of seizure?

And epilepsy?

A

Seizure: abnormal synchronization and excessive excitation of cortical neurons

Epilepsy: a tendency to have recurrent seizures unprovoked by acute systemic or neurologic insults

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

What are the different categories and types of seizures?

just names

A
  • Generalized Seizures (Grand Mal / Tonic-Clonic, Petit Mal / Absence, Myoclonic, Atonic).
  • Partial Seizures (Simple Partial, Complex Partial). Can progress to generalized seizure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the difference between generalized and partial/focal seizures?

What is the difference between the two kinds of partial seizures?

A

Partial seizures affect only one part of brain, whereas in generalized seizures the whole brain is showing similar EEG activity

Simple partial seizures: no loss of consciousness. Complex partial seizures: patient loses consciousness.

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

What are the stages of a Grand Mal seizure?

A
  • Phase 0: “Aura” before seizure, may have acoustic/visual hallucinations
  • Phase 1: Tonic phase with stretched muscles. Cannot breathe, but usually won’t last long enough to be a problem
  • Phase 2: Clonic phase with jerking of large muscle groups. Respiration occurs, but may bite own tongue. May see foam coming out of mouth
  • Phase 3: Postictal tenebrosity (confusion) - stupor, slowly regaining awareness.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the dangerous condition when seizures occur repeatedly after each other or a seizure lasts for abnormally long time?

(seizure lasts more than 5 minutes or so, maybe up to 30 minutes before it can fully be considered this… there doesn’t seem to be a clear agreement on how long)

A

Status epilepticus (prolonged depolarization of neurons -> cellular swelling -> irreversible neurological damage. Also may have neurological damage due to impaired breathing)

Needs acute treatment to stop the seizure

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

What occurs in petit mal seizures?

A

Aka “Absence seizure” - usually in children where they have short-term loss of consciousness. Child stares at nothing for a few seconds, then comes back. See 3Hz EEG spikes in all threads.

If they are very frequent, they can lead to very poor cognitive development of the child (can’t learn)

Drugs that are effective against absence seizures usually have to inhibit T-type Ca2+ channels. [The problem w/ absence seizures originates in the thalamus, and can think of “T-type” for “Thalamus”]

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

What are atonic seizures?

What are tonic seizures?

A
  • Atonic seizure: “drop attack” - child loses consciousness then collapses
  • Tonic: Extensor muscles have increased tone for < 60 seconds
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are myoclonic seizures?

A

Pt loses consciousness, then has some jerking muscle movement. Usually after waking. Occurs mostly in puberty / young adults.

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

What is West syndrome?

A

Aka “Infantile Spasms” - repeated seizures occurring before 1 y/o.

May resolve on its own with time, or may progress to be part of Lennox-Gastraut syndrome with repeated seizures and poor mental development.

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

What is a Jacksonian seizure?

A

Series of focal seizures (simple partial) that start in one group of muscles and spreads systematically to adjacent groups.

Occurs on one side of body, and progresses in predictable pattern.

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

What is/are the mechanism(s) of action of Valproate / Valproic Acid?

A
  • Inhibits VG Na+ channels
  • Inhibits T-type Ca2+ channels
  • Enhances GABA transmission
  • Maybe even decreases Glu transmission
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the indications for Valproate?

A
  • All types of epilepsy (including absence seizures) - broad spectrum antiepileptic
  • Bipolar disorder (manic phase)
  • Migraine prophylaxis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the adverse effects of Valproate?

A
  • Teratogenic: spina bifida
  • Hepatotoxicity (toxic metabolite, high risk in children)
  • Thrombocytopenia, anemia, pancytopenia
  • Pancreatitis
  • Alopecia
  • Neurological symptoms: somnolence, dizziness, headache, tremor
  • Usually weight gain
  • Inhibits CYP450 activity so other drugs can build up in system [note that most anticonvulsants speed up CYP450 metabolism]
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are 3 important points about adverse effects of anticonvulsants in general?

A
  • Most drugs have significant adverse effects, and so patient compliance is low. Epileptics are usually not allowed to drive unless they have been stabilized on medication (no seizures for ~6 months at least), and so there is an incentive to lie to their physician in order to keep their driver’s license.
  • The drugs need to be taken on an uninterrupted regimen. Missing a dose will likely lead to more severe seizures or even status epilepticus
  • Most are teratogenic. Phenobarbital is DOC during pregnacy of epileptics (according to Kaplan).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Valproate kinetics:

  • How is protein binding?
  • Where is it biotransformed?
  • How long is the half-life?
A
  • Significant protein binding
  • Biotransformation in the liver
  • Half-life 10-12 hours
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is/are the mechanism(s) of action of Lamotrigine?

A
  • Inhibits VG Na+ channels
  • Reduce Glu release (inhibits presynaptic Na+ channel)
  • Maybe inhibits T-type Ca2+ channel
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the indications of Lamotrigine?

A
  • Partial epilepsy
  • Generalized tonic-clonic epilepsy
  • Absence seizures
  • Lennox-Gastaut syndrome
  • Bipolar disorder: preventing depression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the adverse effects of Lamotrigine?

A
  • Neurological symptoms
  • Severe skin symptoms that may progress to Stevens-Johnson

[Kaplan says that although this is a newer drug, it’s not been shown to have less side effects than the older drugs and so it’s not normally used except as adjunct therapy]

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

Lamotrigine kinetics:

  • How is protein binding?
  • Where is it biotransformed?
  • How does it affect enzyme metabolism?
A
  • Medium protein-binding
  • Glucoronidation in liver
  • Doesn’t have the characteristic enzyme-inducing effect of most anticonvulsants
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is/are the mechanism(s) of action of Topiramate?

A
  • Inhibits AMPA Glutamate receptors
  • Inhibits VG Na+ channels
  • Inhibits L-type Ca2+ current
  • Carbonic Anhydrase inhibition (causes some metabolic acidosis which lowers threshold for seizures)
  • GABA-A agonism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the indications for Topiramate?

A
  • Partial epilepsy
  • Generalized tonic-clonic epilepsy
  • Lennox-Gastaut syndrome
  • Migraine prophylaxis, tremor, alcoholism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the adverse effects of Topiramate?

A
  • Neurological symptoms (i.e. somnolence, paresthesia)
  • Kidney stones
  • Teratogenic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is/are the mechanism(s) of action of Carbamazepine?

A

-Blocks neuronal Na+ channels in their inactive state (same as phenytoin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the indications of Carbamazepine?

A
  • Partial or General Tonic-Clonic Seizures (but definitely NOT absence, can induce seizures for them)
  • Trigeminal neuralgia, neuropathy, bipolar disorder, alcohol withdrawal
25
Q

What are the adverse effects of Carbamazepine?

A
  • Neurological depression (somnolence etc)
  • Leukopenia, aplastic anemia, megaloblastic anemia
  • Edema, hyponatremia (ADH effect)
  • CYP450 induction (even increases its own metabolism.. higher doses have less than predicted effect as a result)
  • Teratogenic: cleft lip + palate, spina bifida
  • Exfoliative dermatitis
26
Q

Carbamazepine kinetics:

  • How is protein binding?
  • Where is it biotransformed?
A
  • Medium protein-binding
  • Metabolized in liver by CYP3A4, and is also an inducer of CYP3A4. Difficult to get the correct dose down when combining with other drugs that also alter the activity of CYP3A4.

(Lippincott also notes that is variably absorbed between different brand/generic versions)

27
Q

What are the indications of Oxcarbazepine?

What is its mechanism?

What are its side effects?

A
  • Used in partial epilepsy. Less potent antiepileptic, but less potent enzyme induction
  • Blocks neuronal Na+ channels
  • Causes some typical anticonvulsant side effects (i.e. somnolence, diploplia), hyponatremia
28
Q

What are the indications of Eslicarbazepine?

What is its mechanism?

What are its side effects?

A
  • Adjuvant treatment of partial epilepsy
  • Blocks neuronal Na+ channels
  • Causes neuro symptoms (i.e. somnolence), vomiting, diarrhea, hyponatremia
29
Q

What is/are the mechanism(s) of action of Phenytoin?

A

-Blocks axonal Na+ channels in their inactive state, preventing seizure propagation

30
Q

What are the indications of Phenytoin?

A

-Partial or Grand Mal seizures (NOT absence - makes them worse)

31
Q

Phenytoin kinetics:

  • What is the unusual way its eliminated?
  • Effect on metabolism
  • How is protein binding
A
  • Above 300 mg dose it has zero order kinetics elimination (non-linear kinetics) - a good drug to mention on the exam as an example if you get a pharmacokinetics topic. Occurs due to saturable enzyme metabolism
  • Induces CYP450s
  • High plasma protein binding
32
Q

What are the adverse effects of Phenytoin?

A
  • Neurological symptoms (nystagmus, dizziness, diplopia, ataxia)
  • Gingival hyerplasia, hirsutism
  • CYP450 induction, abnormal drug metabolism
  • Hematological (aplastic anemia, megaloblastic anemia)
  • Teratogenic: cleft lip + palate
33
Q

What is different about fosphenytoin from regular phenytoin?

A

Fosphenytoin is only used parenterally (typically IM). [Cannot give phenytoin IM bc it will cause necrosis]

(Ethotoin is a drug similar to phenytoin, given orally)

34
Q

What is the mechanism of Ethosuximide?

What type of seizures is it indicated for?

A

Blocks thalamic T-type Ca2+ channels

Used ONLY for Absence / Petit Mal seizures. [Not used in Hungary so maybe don’t need to know much at Semmelweis, but it’s pretty heavily emphasized in books/Kaplan]

35
Q

What are the adverse effects of Ethosuximide?

A
  • Nonspecific: Fatigue, GI distress, Headache, Dizziness
  • Dermatological: itching, Stevens-Johnson syndrome.
  • Maybe can provoke Grand Mal seizures
36
Q

What are two barbiturate drugs used as anticonvulsants?

What is their MOA?

A
  • Phenobarbital: enhances effects of GABA on GABA-A and Na+ blockade
  • Primidone: converted to active metabolites Phenobarbital and Phenylethylmalonamide

Not great for everyday seizure prophylaxis due to strong sedation. Kaplan says Phenobarbital is considered safest during pregnancy, but no idea what Semmelweis staff thinks about that.

37
Q

The rare type of epilepsy PCDH19 can be an indication for which new drug?

A

Ganaxolone

GABA-A positive allosteric modulator

38
Q

What is the MOA of Vigabatrin?

What is it indicated for?

A
  • Selective irreversible GABA-transaminase inhibitor (decreases GABA breakdown)
  • Used for partial and secondarily generalized seizures. Works well in West syndrome to prevent developing to Lennox-Gastraut syndrome (used as temporary treatment before switching to another med so that vision loss doesn’t occur; max 2 years on Vigabatrin)
39
Q

What are the adverse effects of Vigabatrin?

A
  • Sedation
  • Irreversible visual field defect (prob the most unique thing)
  • May provoke psychosis
40
Q

What is the MOA of Tiagabine?

What is it indicated for?

A
  • Blocks GABA uptake, allowing longer GABA binding/effects

- Adjunct therapy in partial seizures

41
Q

What is the MOA of Gabapentin?

What is it indicated for?

A
  • Although it’s a GABA analog, doesn’t work on GABA receptors. Not precisely known mechanism, but it does seem to block N-type Ca2+ channels on Glutamatergic (excitatory) neurons.
  • Adjuvant therapy in partial seizures and grand mal. Also neuropathic pain, or off-label maybe in anxiety or bipolar disorder [pharma companies have gotten in some trouble for marketing gabapentin for many psych disorders for which it was never FDA approved]
42
Q

How are the pharmacokinetics (uptake protein binding, excretion) of Gabapentin?

What are the adverse effects?

A
  • Nonlinear pharmacokinetics due to saturatable uptake. Doesn’t bind proteins and is excreted unchanged by the kidneys
  • Few adverse effects, possibly better for elderly. Adverse effects may include dizziness, drowsiness, obesity, ataxia.
43
Q

What is the MOA of Pregabalin?

What is it indicated for?

A
  • Binds to α2-δ site of N-type Ca2+ channels on Glutamatergic (excitatory) neurons, inhibiting them
  • Adjuvant in partial and grand mal seizures. Also neuropathic pain, fibromyalgia, GAD, etc. [Pregabalin has also had some shady marketing practices in the US]
44
Q

What is the MOA of Felbamate?

What is it indicated for?

A
  • Many proposed MOAs, but most uniquely it blocks the excitatory NMDA receptor. Also is GABA-A positive modulator. (Riba said something like the company that makes it doesn’t know or doesn’t want to reveal how it works)
  • Reserved only for refractory epilepsies (particularly Lennox-Gastaut syndrome) due to high risk of aplastic anemia and liver failure
45
Q

What is the MOA of Acetazolamide?

What type of epilepsy is it indicated for?

A
  • Carboanhydarase inhibitor (makes a metabolic acidosis that reduces seizures)
  • Used (rarely) in women who have seizures at time of menses. (Lot of other uses out there, prob will cover it in other topics)
46
Q

What are the MOAs of Zonisamide?

What type of epilepsy is it indicated for?

What are the adverse effects?

A
  • Carboanhydrase inhibition, inhibition of Na+ and Ca2+ channels, GABAergic, maybe Glutamatergic effects
  • Broad spectrum, but usually adjuvant or monotherapy in focal epilepsy
  • Sedation and other neuro effects, weight loss, kidney stones
47
Q

What is the MOA of Lacosamide and Rufinamide?

-What are they indicated for?

A
  • Inhibit Na+ channels
  • Adjuvants in partial and secondarily generalized seizures. Rufinamide can be used in Lennox-Gastraut syndrome (including for absence seizures, which is unique for Na+ channel blockers)
48
Q

What is the MOA of Levetiracetam?

What is it indicated for?

A
  • Exact MOA is unclear. Inhibits N-type Ca2+ channels and also binds synaptic vesicular protein 2A (prevents fusion of vesicle and membrane in excitatory neurons)
  • Usually adjunct but can be monotherapy with new patients for Focal, Myoclonic, and Grand Mal seizures.
49
Q

What is the MOA of Retigabine?

What is it used for?

A
  • Opens neuronal-type KCNO/Kv7 K+ channels (only one of these that’s a potassium channel blocker)
  • Used as adjuvant for partial seizures
50
Q

What are the MOAs of Stiripentol?

What is it indicated for?

A
  • Inhibits GABA transaminase and reuptake. Barbiturate-like effect (opens GABA for longer)
  • Indicated in severe myoclonic epilepsy in infancy (SMEI, Dravet’s syndrome)
51
Q

What drugs are used to treat Petit Mal / Absence seizures?

A
  • First line is Valproic Acid. Can use some other broad-spectrum antiepileptics
  • Benzodiazepines, esp. Clonazepam
  • Ethosuximide (works only for petit mal), but not used in Hungary

(definitely do NOT use Phenytoin nor Carbamazepine)

52
Q

What are the 4 most important “broad spectrum” anti-epileptics to know?

A
  • Valproic Acid
  • Topiramate
  • Lamotrigine
  • Zonisamide

(Have seen some include levatiracetam, felbamate, acetazolamide in with these.. but the above are all classic broad spectrum bc they are used for all types of epilepsy, including absence seizures)

53
Q

What drugs can be given in case of status epilepticus?

A
  • Preferred: Benzos IV and in high dose: Diazepam, Lorazepam (maybe also Clonazepam)
  • Phenytoin or fosphenytoin IV (may also be considered first line)
  • Phenobarbital IV (second choice)
54
Q

What are the anti-epileptics that are mainly just Na+ channel blockers?
(non-broad spectrum, usually can’t use these for absence seizures)

A
  • Phenytoin
  • Carbamazepine
  • Oxcarbazepine
  • Lacosamide
  • Rufinamide (only one that might sort of work for absence seizures as part of Lennox-Gastraut syndrome, unclear why)
55
Q

Which GABA-ergic drugs are used as antiepileptics?

5 listed

A
  • Benzodiazepines (especially diazepam, lorazepam, and clonazepam)
  • Vigabatrine
  • Tiagabin
  • Stiripentol
  • Barbiturates (Phenobarbital)
56
Q

Which anti-epileptic has its main mechanism as a T-type Calcium Channel Blocker? (not a broad spectrum)

A
  • Ethosuximide

- (Trimethadione is another one but probably won’t be on the market anywhere, it’s more toxic and hormonally supressive)

57
Q

What is the MOA of Sulthiame?

What is it indicated for?
[prob a low-yield drug, older]

A
  • Weak carbonic anhydrase inhibition (mild metabolic acidosis suppresses epilepsy)
  • Used in a special type of absence epilepsy: Roland Epilepsy. But some people think this is so benign that it doesn’t even need treatment
58
Q

What is the MOA of Perampanel?

What is it indicated for?
[new drug so maybe won’t find it in books]

A
  • AMPA antagonist (see AMPA in the name…)

- Used for primary generalized tonic clonic seizures

Pharmacology (Dustin, Ben) (17 decks)

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