Brainscape's Knowledge GenomeTM

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


See full index

Pharm Exam 2 > Bannon: Anti-seizure Drugs > Flashcards

Bannon: Anti-seizure Drugs Flashcards

1
Q

Seizure

Definition:

A

Definition: finite episodes of brain dysfunction resulting from abnormal discharge of cerebral neurons

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

Types: (6)

A 
Partial Seizures (Simple)
Partial Seizures (Complex)
Tonic-Clonic Seizures (Generalized)
Absence Seizures (Generalized)
Monoclonic Seizures
Status Epilepticus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Partial Seizures (Simple)

Consciousness:
Various manifestations: (4)

A

Consciousness preserved (simple)

Various manifestations:

  • Convulsive jerking
  • Paresthesias
  • Psychic symptoms (altered sensory perceptions, illusions, hallucinations, affect changes)
  • Autonomic dysfunction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q 
Partial Seizures (Complex)
Consciousness:
A 
Partial Seizures (Complex):
o	Impaired consciousness (complex) that is preceded, accompanied, or followed by psychologic symptoms
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Tonic-Clonic Seizures (Generalized):

A

Tonic phase involves abrupt LOC, muscle rigidity and respiration arrest (less than 1 minute)

Clonic phase involves jerking of body muscles, with lip or tongue biting, and fecal and urinary incontinence (2-3 minutes)

Formerly called grand mal seizures

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

Absence Seizures (Generalized):

A

Impaired consciousness (often sudden onset and brief)

Sometimes accompanied by automatisms, loss of postural tone, or enuresis

Begin in childhood and usually cease by age 20

Formerly known as petit mal seizures

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

Myoclonic Seizures:

A

Single or multiple myoclonic jerks

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

Status Epilepticus:

A

A series of seizures (usually tonic-clonic) without recovery of consciousness between attacks

Life-threatening emergency

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

Risk Factors

Children:
Adults:
Elderly:

A

Children: fever, mental retardation, cerebral palsy, genetics

Adults: trauma, tumors

Alzheimer’s Disease, Stroke

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

First Generation Drugs
Use:
Effective for the treatment of: (2)

A

Use: effective for the treatment of generalized tonic-clonic and partial seizures

  • Many rate-dependently prolong inactivation of voltage-gated Na channels (similar to lidocaine)
  • Others potentiate GABA by several mechanism

Use: effective against generalized (absence) seizures
- Thought to block T-type Ca channel-mediated current in thalamic neurons

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

Newer Drugs

Newer Phenotypic Models:
Targeting of Defined Biochemical Mechanisms:
Novel AD Targets:

A

Newer Phenotypic Models: mutant mice, models of kindling or neuropathic pain

Targeting of Defined Biochemical Mechanisms: GABA uptake, metabolism, receptor effects

Novel AD Targets: glutamate receptors (NMDA), K+ channels (open to hyperpolarize) or Ca++ channels

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

Drugs with Broad Spectrum of Action:

A

May be due to multiple mechanisms of action and/or novel mechanisms of action

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

Drugs for Partial and Generalized Tonic-Clonic Seizures

Drugs of Choice: (3)

A

o Phenytoin (Dilantin)
o Carbamazepine
o Valproic Acid

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

Phenytoin (Dilantin)

History:
MOA:

A

History: oldest nonsedative antiseizure drug

MOA: blockade of Na channels is the strongest effect (but not the only effect) at therapeutic concentrations

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

Phenytoin (Dilantin)

Absorption:
Elimination:

A

Absorption: highly dependent on the formulation
o Fosphenytoin: soluble prodrug that allows for IM or IV administration

Elimination: via the liver; dose-dependent and need to titrate dose slowly

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

Phenytoin (Dilantin)

Toxicity/Side Effects: (4)

A

Nystagmus early

Diplopia and ataxia are dose-limiting effects

Gingival hyperplasia and hirsutism are common long-term

Idiosyncratic reactions are rare

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

Drugs for Partial and Generalized Tonic-Clonic Seizures
Phenytoin (Dilantin)

Use:

A

Use: considered a 2nd line drug by some, but still one of the most widely used drugs in the world

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

Carbamazepine
Structure:
Other Uses (Besides Seizures): (3)

A

Structure: tricyclic compound related to some antidepressants

Other Uses (Besides Seizures):

  • Treatment of BPD
  • Treatment of trigeminal neuralgia
  • Drug abuse (?)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Carbamazepine

MOA:

A

MOA: blockade of Na channels is the primary effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Carbamazepine

Metabolism:

A

Metabolism: significant microsomal induction and may have to adjust dose of this and other drugs over time (ie. induces its own metabolism)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Carbamazepine
Toxicity/Side Effects: (3)
Side effects may be decreased with:

A
  1. Diplopia and ataxia (dose-related)
  2. Idiosyncratic blood dyscrasia in the elderly
  3. Stevens-Johnson Syndrom (rare but serious skin reaction)
    o Genetic risk determined by presence of a specific HLA allele (testing recommended by FDA)
    o 10x higher risk in Asians

Side effects may be decreased with ER formulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Carbamazepine

Important:

A

Important: may exacerbate myoclonic and absence seizures (do not use for these)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Valproic Acid

Use in Seizures: (6)

A
  • Partial seizures
  • Generalized tonic-clonic
  • Myotonic seizures
  • Atonic seizures
  • Generalized (absence) seizures
  • Combination seizures
24
Q 
Valproic Acid
Other Uses (Besides Seizures):
A

Treatment of BPD

Treatment of migraine (Divalproex sodium ER)

25
Q

Valproic Acid
MOA:

  • Blockade of:
  • GABA
  • Histone deacetylation inhibition
  • Ca++ channels
A

MOA: unclear; broad spectrum of action most likely due to multiple MOA

  • Blockade of Na channels possible
  • GABA effects may also be relevant
  • Histone deacetylation inhibition to INCREASE gene expression (potentiation of Sp transcription factor family –> turns on a bunch of genes)
  • May also have effects on Ca++ channels (due to efficacy against absence seizures)
26
Q

Valproic Acid

Side Effects:

A

Side Effects: serious effects are rare, but may not be first line due to these rare events
- Severe idiosyncratic hepatotoxicity (requires monitoring of liver function)

27
Q

Valproic Acid

Formulations:

A

Divalproex Sodium ER: used once daily

  • Complex partial seizures
  • Absence seizures
  • Migraine
28
Q

Alternative Drugs for Treatment of Seizures: (5)

A 
Phenobarbital
Lamotrigine
Levetiracetam
Gabapentin and Pregabalin (Lyrica)
Topiramate (Topamax)
29
Q

Phenobarbital

MOA:
Use:
Side Effects:

A

MOA: potentiate GABA effects

Use: rapid effects, safety profile and low cost can make it a DOC

Side Effects: sedative effects can be limiting

30
Q

Lamotrigine

MOA:
Use:
Side Effects:

A

MOA: blockade of Na channels; may have additional MOAs due to broad spectrum of activity

Use: shown to be as effective as the DOCs (may now be considered one)

Side Effects: rare but life-threatening dermatitis possible in infants

31
Q

Levetiracetam

MOA:
Use:
Side Effects:

A

MOA: binds SV2A to interfere with release of NT

Use: very good for refractory seizures in adults and children (another possible DOC)

Side Effects: well tolerated

32
Q

Gabapentin and Pregabalin (Lyrica)

MOA:
Other Uses (Besides Seizures): (4)
A

MOA: binds voltage gated Ca channel subunit (not related to GABA)

Other Uses (Besides Seizures):

  • Neuropathic pain
  • Migraine
  • Anxiety
  • Surgical analgesia
33
Q

Topiramate (Topamax)

MOA:
Use:
Side Effects:

A

MOA: broad spectrum drug, probably with multiple MOAs

Use: hot drug for off-label use

  • Refractory migraine
  • BPD
  • Many other disorders

Side Effects: typical CNS side effects and memory problems

34
Q

Drugs for Generalized (Absence) Seizures

Drugs of Choice: (3)

A

Ethosuximide
Valproic Acid
Clonazepam

35
Q

Ethosuximide

Use:
MOA:

A

Use: A first line drug for absence seizures ONLY (no other types)

MOA: blocks T-type Ca++ channel

36
Q

Ethosuximide

Absorption:
Metabolism:
Toxicity:

A

Pharmacokinetics:

  • Absorption: good
  • Metabolism: complete

Toxicity: well tolerated

  • Dose-related gastric distress
  • More rare instances of rashes and psychosis
37
Q

Clonazepam

Use: (4)

A
  • Absence seizures (may be less effective that ethosuximide or valproic acid)
  • Myoclonic seizures
  • Atonic seizures
  • Infantile spasms
38
Q

Clonazepam

Side Effects: (3)

A

Side Effects: typical benzo side effects that limit use

  • Sedation
  • Development of tolerance
  • Withdrawal syndrome
39
Q

Treatment of Status Epilepticus

Treatment:
Important Point:

A

Treatment:
o IV diazepam or lorazepam
o Followed by IV fosphenytoin or phenobarbitol

Important Point: watch for synergistic CNS depression when combining these drugs!

40
Q

Other Aspects of Antiseizure Drug Therapy
Teratogenicity

Difficult to assess:

A

Teratogenicity: Difficult to assess due to seizures and heterogeneity of these medications

  • Most pregnant patients on these drugs deliver normal infants
  • Apparent overall 2X increase in risk of congenital malformations when on the drugs (no increased risk if off the drugs during pregnancy)
  • If you choose to keep them an a drug (which is typically done), use the lowest effective dose of monotherapy
41
Q

Other Aspects of Antiseizure Drug Therapy
Teratogenicity

Specific Known Risks: (2)

A

Phenytoin: fetal hydantoin syndrome (?)

Valproic Acid: risk of spina bifida (1-2%) and possible effect on IQ

42
Q

Other Aspects of Antiseizure Drug Therapy

Drug Withdrawal:

A

Most difficult for people on benzodiazepines and barbiturates

~70% of people with epilepsy enter remission while on medications (>5 years seizure free)

~75% of these patients can be successfully and gradually withdrawn from their medications

43
Q

Other Aspects of Antiseizure Drug Therapy

Other:

A

Increased suicide risk (2X)

Decreased bone density (chronic use)

44
Q

Future of Pharmacotherapy for Seizures:

A

Large number of candidate drugs being identified through high-throughput screening

Some have novel MOAs and should be useful/improve the treatment of refractory epilepsy

Improved understanding of genetic and cellular basis for epilepsy will lead to more precisely targeted therapeutics and new strategies to delay/prevent epileptogenesis

45
Q

Ketogenic Diet

History:
Description:
Use:

A

History:
o Fasting formerly used to treat epilepsy
o Lost favor because of practical difficulties and antiquated medical theories

Use:
o Treatment of refractory seizures in children (ie. Lennox-Gastaut Syndrome)

46
Q

Ketogenic Diet

Description:

A

Description:
o Low calorie diet with 4 grams of fat per gram of protein or carbs
o Diet creates ketones by fat metabolism (mimics fasting) and ketones replace glucose as fuel
o Not entirely clear what the MOA of this diet is with regard to seizure treatment
o Strict adherence is required (children need to initially be hospitalized to ensure adherence)

47
Q

Anterior Temporal Lobectomy

Use:
Results:

A

Use: very effective for refractory and harmful cases of the most common partial seizure of adults

Results: most patients seizure free for 5 years (enter remission)

48
Q

Corpus Callostomy

Use:

A

Lennox-Gastaut Syndrome (difficult to treat childhood onset form of epilepsy characterized by frequent and different types of seizures)

49
Q

Hemispherectomy

Use: (2)

A

Use: other severe forms of childhood epilepsy

  • Ramussen Syndrome (rare chronic inflammatory neurological disorder)
  • Sturge Weber Syndrome (rare congenital neurological and skin disorder)
50
Q

Vagus Nerve Stimulation (NeuroCybernetic)

Use: (4)

A
  • Refractory complex partial and generalized seizures
  • Poor surgical candidates
  • Now being tested in children
  • Also used in depression, anxiety and other disorders
51
Q

Vagus Nerve Stimulation (NeuroCybernetic)

Response:

A

Response: MOA is unclear but clearly effective

- Good response (seizure reduction in 30-75% of patients)

52
Q

Therapeutic Principles for the Management of Epilepsy

Pre-Therapy:

A

Pre-Therapy:

  • Determine cause of seizures if possible
  • For children, wait and see before treating after a single, unprovoked seizure
53
Q

Therapy

Partial Seizures and Generalized Tonic-Clonic: (3)
Possibly: (3)

A

Partial Seizures and Generalized Tonic-Clonic: phenytoin, carbamazepine, valproic acid

Possibly: phenobarbital, lamotrigine, levetiracetam

54
Q

Therapeutic index and toxicity:

Need to ensure:

A

Therapeutic index and toxicity not uncommon with most antiseizure drugs, so need to ensure adequate trial of a single drug AND monitor plasma levels closely

55
Q

Cases of Treatment Failure:

A

Occurs in as many as ½ of patients- first try monotherapy with another first line drug

If total pharmacological failure (20-30% of patients), consider surgery or vagal nerve stimulation

Pharm Exam 2 (13 decks)

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