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Pharm 2 Part 1 > Lecture 7: Anticonvulsants > Flashcards

Lecture 7: Anticonvulsants Flashcards

1
Q
  1. What is a PARTIAL SEIZURE?
A
  1. Starts FOCALLY in a CORTICAL SITE and May Spread
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2
Q

Simple Partial?

A

Jerking, lasts about 20 seconds w/preservation of consciousness

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3
Q

Complex Partial

A

Impairment of Consciousness < 2 min. Usually start in Temporal Lobe

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4
Q

Partial w/Secondary Generalized Tonic-Clonic

A

Starts as Partial seizure then turns into Tonic Clonic: Loss of Consciousness, muscle contractions alternating w/Relaxation

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5
Q

What is Generalized Seizures?

A

Involve both hemispheres from the outset

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6
Q

Tonic-Clonic (Grand Mal)

A

Lose consciousness, muscle contractions, generalized

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7
Q

Absence (petit mal)

A

Staring, cease activity; usually less than 30 seconds

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8
Q

Myoclonic

A

brief shock-like muscle contraction; may be part of 1 extremity or general

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9
Q
  1. What produces Seizures?

a. What does this suggest?

A
  1. Blocking GABA receptors, or injection of GLUTAMATE RECEPTOR AGONISTS
    a. Under-activity of GABAergic neurons, or over-activity of Glutamate transmission
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10
Q
  1. WHEN can PARTIAL SEIZURES TEND to DEVELOP after HEAD INJURY or STROKE?
A
  1. Usually YEARS AFTER
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11
Q
  1. What is a HYPEREXCITABLE STATE called?

a. What inhibits seizures in this model?

A

KINDLING…induced in animals via low intensity electrical stimulation of the AMYGDALA or other LIMBIC STRUCTURES

a. Inhibiting NMDA Receptors

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12
Q

Drugs used for Absence Seizures are used to do what?

A

Block a Voltage Gated Ca2+ channel (T CURRENT)

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13
Q

What 4 drugs act by Blocking Na+ channels, prolonging closure and Inhibiting Glutamate Activity? (PCLV)

A

PHENYTOIN, CARBAMAZEPINE, LAMOTRIGINE, and VALPROIC ACID

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14
Q

Blockage of Thalamic Low Threshold Calcium Current. (T-current): What 2 drugs work to block this channel?

A

ETHOSUXIMIDE and VALPROIC ACID

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15
Q

Enhancement of GABA Activity

  1. What 2 drugs increase GABA activity, and increase HYPERPOLARIZATION of Neurons by opening Cl- Channels?
A

BENZODIAZEPINES and PHENOBARBITAL

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16
Q

Drugs used in Partial and Generalized Tonic-Clonic Seizures

  1. Phenytoin
    a. What does it block?
    b. Very effective against what 2 types of seizures?
    c. NOT EFFECTIVE against what?
A
  1. a. High frequency, repetitive firing of neurons by prolonging inactivation of Na+ channel
    b. Partial and Generalized Tonic-Clonic
    c. Absence
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17
Q

Drugs used in Partial and Generalized Tonic-Clonic Seizures

  1. Phenytoin: Pharmacokinetics
    a. How is it put into the body?
    b. Elimination depends on what?
    c. At this point, small changes in dose may do what?
    d. Half life range?
A
  1. a. PARENTERAL
    b. Dose-Dependent. 1st order metabolism at low blood levels, but it becomes 0 order when liver reaches max capacity
    c. Means LARGE CHANGES in BLOOD LEVEL
    d. 12-36 hrs
18
Q

Drugs used in Partial and Generalized Tonic-Clonic Seizures

  1. Phenytoin: Drug Interactions
    a. Metabolism is saturated at THERAPEUTIC CONCENTRATIONS, addition of other drugs may do what?
    b. It induces microsomal enzymes and will increase METABOLISM of drugs like what?
A
  1. a. metabolized by same enzymes may inhibit phenytoin metabolism by a lot
    b. like Oral Contraceptives
19
Q

Drugs used in Partial and Generalized Tonic-Clonic Seizures

  1. Phenytoin: Toxicity
    a. What happens in 20-30% of PATIENTS?
    b. Can it be used in PREGNANCY?
A
  1. a. GINGIVAL HYPERPLASIA

b. No. Category D. TERATOGEN w/SERIOUS BIRTH DEFECTS.

20
Q

Drugs used in Partial and Generalized Tonic-Clonic Seizures

  1. Carbamazepine
    a. Like Phenytoin. What does it do?
    b. What other effect does it have?
    c. DOC for what seizures?
    d. Also widely used as FIRST DOC for what?
    e. Effective at HIGH doses for what issue?
    f. Not very sedating in what level of doses?
A
  1. a. Blocks Na+ channels and Decreases NT release
    b. Mood-Stabilizing EFFECT (used for Tx of BIPOLAR DISORDER)
    c. PARTIAL SEIZURES
    d. Generalized Tonic-Clonic Seizures
    e. for TRIGEMINAL NEURALGIA
    f. in Normal Therapeutic Doses
21
Q

Drugs used in Partial and Generalized Tonic-Clonic Seizures

  1. Carbamezapine: Pharmacokinetics
    a. What does it induce?
A
  1. a. CYP3A that metabolizes Oral contraceptives and induces its own metabolism.
22
Q

Drugs used in Partial and Generalized Tonic-Clonic Seizures

  1. Carbamezapine: Drug Interactions
    a. Increases Metabolism of what durgs? Lots of them…look at page.
A

dafsfg

23
Q

Drugs used in Partial and Generalized Tonic-Clonic Seizures

  1. Carbamezapine: Toxicity
    a. What allele is affected?
    b. This allele is seen in whom?
    c. If they test positive for it, what should they do?
    d. Pregnancy?
A
  1. a. HLA-B1502
    b. South Asian Indians and Asia…
    c. Don’t take the drug unless benefit outweighs the risk. If they take it for a few months w/o developing skin reactions then they’re at low risk.
    d. Category D.
24
Q

Drugs used in Partial and Generalized Tonic-Clonic Seizures

  1. Phenobarbital and Primidone
    a. What do they do to the GABA receptor?
    b. What side effects do they cause? (2)
    c. What is PRIMIDONE metabolized to?
    d. CONTRAINDICATED in what?
    e. Pregnancy?
A
  1. a. Prolong opening of Cl- channel at GABAa receptor
    b. Drowsiness and generalized CNS depression
    c. Phenobarbital
    d. PORPHYRIA
    e. Category D
25
Q

Drugs used in Partial and Generalized Tonic-Clonic Seizures

  1. Lamotrigine
    a. What does it do?
    b. What do we think it decreases the release of?
    c. Often effective in Tx in what disorder?
  2. Toxicity
    a. Pregnancy?

b. What else?

A
  1. a. Inactivates VG-Na+ channels
    b. Glutamate
    c. of Bipolar disorder
  2. a. Category C (use only if necessary)
    b. Skin rash (suggests HYPERSENSITIVITY so stop taking it!); Dermatitis…can be LIFE THREATENING in CHILDREN; Dizzy, headache, double vision, nausea
26
Q

Drugs used in Partial and Generalized Tonic-Clonic Seizures

  1. Topiramate
    a. What does it Block?; Enhance?; Decreases what?
    b. Could decrease effectiveness of what?
    c. Approved for use in what?
    d. Broad spectrum?
  2. Side Effects
    a. Pregnancy?
    b. Other issues?
A
  1. a. VG-Na+ channels; GABAa Current; Glutamate Receptor activation
    b. of oral contraceptives
    c. prophylaxis tx of migraine
    d. Useful in many seizure disorders
  2. a. Category C (birth defects possible)
    b. dizzy, fatigue, sedation, acute myopia and glaucoma may require STOPPING DRUG IMMEDIATELY!!
27
Q

Drugs used in Partial and Generalized Tonic-Clonic Seizures

  1. Gabapentin and Pregabalin

a. Analogs of what?
b. What might they Augment?
c. What channels do they block?

d. Pregabalin also used for Tx of what?
e. Both drugs excreted by what?
f. Length of time?
g. Side effects?
h. Pregnancy?

A
  1. a. GABA (don’t act on receptors)
    b. GABA release
    c. N-Type Ca2+ channels, and inhibit release of Glutamate
    d. Fibromyalgia
    e. Kidney
    f. 5-8 hrs
    g. Dizziness, drowsiness, ataxia, headache, tremor, weight gain
    h. Category C: TERATOGENIC in ANIMALS
28
Q

Drugs used in Absence Seizures

  1. Ethosuximide
    a. DOC for what?
    b. What does it block?
    c. Given 2x’s a day. Why?
    d. ONLY SIGNIFICANT DRUG INTERACTION?
  2. Toxicity

a. major issues?
b. Pregnancy?

A
  1. a. Absence seizures
    b. T-type Ca2+ channels
    c. to decrease GI effects
    d. Valproic acid decreases its clearance
  2. a. GI most common. Headache.
    b. Category C
29
Q

Drugs used in Absence Seizures

  1. Valproic Acid/Sodium Valproate
    a. Blocks what channels?
    b. What Receptor stimulation does it decrease?
    c. May INCREASE synthesis and levels of what hormone?
    d. Very Effective against what 2 types of Seizures?
    e. When is it the DOC?
    f. Also effective against what other seizures?
    g. Where else is it used?
A
  1. a. Na+ Channels and HIGH-FREQUENCY Repetitive Firing
    b. NMDA
    c. of GABA
    d. Absence and generalized Tonic-Clonic Seizures
    e. when both of these SEIZURES occur together
    f. Myoclonic Seizures
    g. Mood stabilizer in Bipolar Disorder and for Prophylaxis of Migraine
30
Q

Drugs used in Absence Seizures

  1. Valproic Acid/Sodium Valproate: DRUG INTERACTIONS
    a. Inhibits its own metabolism at what dosage?
    b. Inhibits metabolism of what other 2 drugs?
    c. Decreases Elimination of what drug?
A
  1. a. Low doses
    b. Carbamazepine and Phenytoin
    c. of Lamotrigine
31
Q

Drugs used in Absence Seizures

  1. Valproic Acid/Sodium Valproate: Toxicity
    a. Most common causes? (4)
    b. Contraindicated in patients with what disease?
    c. Pregnancy? Known to CAUSE what?
A
  1. a. Abdominal pain, Heartburn, Nausea, Vomiting
    b. Liver Disease
    c. CATEGORY D; cause BIRTH DEFECTS!
32
Q

Diazepam and Lorazepam

  1. a. How is it given?
    b. DOC? Causes death in what % of pts?
    c. SHOULD not be given to whom? Except in what situation?
A
  1. a. IV
    b. for STATUS EPILEPTICUS; 20% of pts
    c. Pregnant women; UNLESS in Serious or LIFE-THREATENING SITUATIONS!
33
Q

Clonazepam

  1. Type of drug?
    a. Useful against what?
    b. Also effective in what 2 situations?
    c. What is common?
    d. Tolerance may develop to what effect?
    e. ALL BENZOS are WHAT?
A
  1. Benzo
    a. ABSENCE SEIZURES
    b. Myoclonic seizures and Infantile Spasms
    c. Sedation
    d. to Antiseizure Effect
    e. PREGNANCY CATEGORY D as they increase risk of Congenital malformation and other developmental abnormalities if used in the first trimester
34
Q

Stevens-Johnson Syndrome

  1. Type of Reaction is it?
    a. Consists of what issues?
    b. How often does it occur?
    c. Most Anticonvulsants have a risk of causing it, but most likely with what Drugs?
A
  1. Hypersensitivity RxN
    a. Erythema Multiforme, Arthritis, Nephritis, CNS issues, Myocarditis.
    b. Rare. 0.1% of the time or less.
    c. Phenytoin, Phenobarbital, Primodine, Lamotrigine, Ethosuximide
35
Q

Anticonvulsants in Pregnancy

Which drugs are Category D? (8)

A
  1. Phenytoin, Carbamazepine, Phenobarbital, Ethosuximide, Valproic Acid, Benzos (Diazepam, Lorazepam, Clonazepam)
36
Q

Anticonvulsants in Pregnancy

Which drugs are Category C? (4)

A

Lamotrigine, Gabapentin, Topiramate, Tiagabine

37
Q

Which 2 Anticonvulsants DID NOT INCREASE SUICIDE RISK?

A

Carbamazepine and Valproate. (no data for PHENYTOIN)

38
Q

Absence Seizures (3)

A
  1. Ethosuximide, Valproic Acid, and Clonazepam
39
Q

Myoclonic Seizures (2)

A

Levetiracetam, Valproic Acid

40
Q

Atonic Seizures (2)

A

Lamotrigine and Valproic Acid

41
Q

Infantile Spams (2)

A

Corticosteroids, and Topiramate

42
Q

Status Epilepticus

  1. Most effective?
  2. What other 2?
A
  1. Diazepam and Lorazepam

2. Phenytoin and Phenobarbital

Pharm 2 Part 1 (6 decks)

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