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NBB Test 2 > Anti-Seizure Drugs (ASDs) 1 > Flashcards

Anti-Seizure Drugs (ASDs) 1 Flashcards

1
Q

What percentage of patients with epilepsy can have their seizures controlled with medication?

A

65-80%

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2
Q

Pharmacotherapy of epilepsy is highly individualized and requires titration of the dose to optimize

A

ASD therapy

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3
Q

Many of the new ASDs are only approved for

A

Adjunct Therapy

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4
Q

ASDs can cause a rash called

A

Steven Johnsons Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN)

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5
Q

Can cause Fetal Abnormalities and birth defects (“Major Congenital Malformations” or MCMs)

A

ASDs

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6
Q

What are the three mechanisms of action of ASDs?

A
  1. ) Modification of ionic conductance
  2. ) Enhancement of inhibitory transmission
  3. ) Inhibition of excitatory transmission
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7
Q

ASDs enhance inhibitory transmission (IPSPs) by increasing

A

GABAergic transmission

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8
Q

ASDs inhibit excitatory transmission (EPSPs) by decreasing

A

Glutamergic transmission

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9
Q

The ability of Na+ channels to recover from inactivated state is inhibited by ASDs. This prolongs the

A

Inactivation state of Na+ channels

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10
Q

Neurons undergo depolarization and fire action potentials at high frequencies during

A

Seizures

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11
Q

Selective inhibition of this pattern of firing should reduce

A

Seizures

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12
Q

Inhibition of the high-frequency firing is thought to be mediated by reducing the ability of Na+ channels to recover from

A

Inactivation

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13
Q

Prolonging the inactivation of the Na+ channels results in reducing the ability of neurons to

A

Fire at high frequencies

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14
Q

Recall that inactivated channels are inactive because they are blocked by the

A

Inactivation gate

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15
Q

Oldest nonsedative antiseizure drug (1938)

A

Phenytoin (Dilantin, Phenytek)

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16
Q

A prodrug of phenytoin designed for parenteral use

A

Fosphenytoin

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17
Q

What is the major mechanism of action of Phenytoin?

A

Na+ Channel Inhibiton

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18
Q

Indications: 1) Simple Partial 2) Complex Partial 3) Secondarily Generalized and 4) Primary Generalized tonic-clonic seizures

A

Phenytoin

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19
Q

What are the contraindications for Phenytoin?

A

May exacerbate myoclonic and absence seizures

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20
Q

Phenytoin is especially contraindicated in

A

Lennox-Gastaut Syndrome

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21
Q

The therapeutic dose for most patients is

A

10-20 ug/mL

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22
Q

Only free, unbound phenytoin molecules can penetrate the bloodbrain barrier and exert

A

Pharmacological effects

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23
Q

What percentage of Phenytoin is bound to plasma protein?

A

90%

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24
Q

Conditions such as hypoalbuminemia and uremia can significantly impact plasma levels of

A

Phenytoin

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25
Q

Phenytoin is eliminated hepatically by conversion to

A

Inactive Metabolites

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26
Q

At low blood levels, phenytoin metabolism follows

A

First-order kinetics

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27
Q

At therapeutic range and higher, non-linear relationship of dosage and plasma concentration occurs. This is

A

Zero order kinetics

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28
Q

Is extensively metabolized in the liver and this process becomes saturated at about the doses needed for therapeutic effect

A

Saturation Kinetics

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29
Q

Thus, phenytoin at low doses exhibits first-order kinetics, but saturation or zero-order kinetics develop as we reach the

A

Therapeutic plasma concentration

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30
Q

Phenytoin is 90% bound to plasma proteins (albumin). Increased proportions of free (active) drug are observed in newborn, in patients with

A

Hypoalbuminemia and in uremic patients

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31
Q

Other protein-binding drugs, including other ASDs (e.g. valproate) can compete for protein binding sites, resulting in increases in

A

Free Phenytoin

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32
Q

Drugs that induce or inhibit hepatic enzymes can impact phenytoin metabolism and thus impact

A

Plasma concentrations

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33
Q

Phenytoin itself induces

A

Hepatic Enzymes

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34
Q

Nystagmus, diplopia, ataxia, drowsiness are common dose-related CNS adverse effects requiring dosage adjustment

A

Phenytoin

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35
Q

Seen in 20-40% of patients chronically taking phenytoin

A

Gingival hyperplasia

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36
Q

Phenytoin can cause vitamin D deficiency which may result in

A

Osteomalacia

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37
Q

A category D (bad) teratogen

A

Phenytoin

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38
Q

What percentage of Carbamazepine is protein-bound?

A

75%

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39
Q

The active metabolite of Carbamazepine is?

A

10,11-epoxide

40
Q

The t½ of Carbamazepine falls significantly over the first few weeks of therapy due to the induction of

-Metabolize itself (autoinduction)

A

Hepatic enzymes (CYPs)

41
Q

CYP-inducing drugs such as phenytoin may increase the metabolism of

A

Carbamazepine

42
Q

What are three common symptoms of Carbamazepine?

A

Hyponatremia, Leukopenia, Rash

43
Q

Can induce Stevens-Johnson Syndrome

-Incidence is highest in Asian Populations

A

Carbamazepine

44
Q

The HLA allele B*1502 (10-15% incidence in ethnic Han Chinese; 2-4% in ethnic South Asian) has been identified as a marker for

A

Carbamazepine-induced SJS and toxic epidermal necrolysis (TEN)

45
Q

FDA approved in 2000 for partial seizures with or without secondary generalization

-Generally fewer adverse effects than CBZ (and phenytoin)

A

Oxcarbazepine (Trileptal)

46
Q

Is more likely to cause hyponatremia than carbamazepine

-Important consideration for patients taking diuretics

A

Oxcarbazepine

47
Q

What are the three mechanisms of action of Valproic Acid (or Valproate)

A

Na+ Channel Inhibition, Inhibition of T-type Ca2+ channels, and Increased GABA produciton

48
Q

Valproic Acid (Valproate) is contraindicated for patients with

A

Liver Disease

49
Q

When the fraction of bound drug reduces as the total concentration of drug is increased

A

Saturable binding

50
Q

Highly protein-bound, but the binding is saturable

A

Valproate

51
Q

Valproate is eliminated through hepatic metabolism, mainly by

A

UGT enzymes and beta-oxidation

52
Q

At least 10 metabolites have been identified, with one at least one (4-ene VPA) being implicated for the hepatotoxicity associated with

A

Valproate

53
Q

Crosses the placenta and concentrations in cord serum blood may be 5-X higher than the mother due to higher binding in the fetal compartment

A

Valproate

54
Q

Enzyme-inducing ASDs (phenytoin, carbamazepine) can decrease the concentration of

A

Valproate

55
Q

Which type of antibiotics reduce valproate serum concentrations?

A

Carbapenems

56
Q

As a high proportion of valproate is bound to albumin, it can displace

A

Phenytoin and other drugs from albumin

57
Q

Can inhibit hepatic enzymes, so it can inhibit the metabolism of other ASDs like phenytoin, phenobarbital, lamotrigine and lorazepam when co-administered

A

Valproate

58
Q

What are the three major side effects of Valproate?

A

Weight gain, hepatotoxicity, and teratogenic effects

59
Q

A rare complication with valproate that is frequently fatal

A

Fulminant hepatitis

60
Q

Has teratogenic effects such as neural tube defects (up to 20-fold higher risk than the general population), particularly spina bifida

A

Valproate

61
Q

Can give a rash in 10% of patients and rarely progresses to serious systemic illness (SJS)

A

Lamotrigine

62
Q

Lamotrigine does not induce or inhibit

A

CYP enzymes

63
Q

While lamotrigine has not been shown to affect the efficacy of oral contraceptives (OCs), it has been reported that OCs can reduce effective concentrations of

A

Lamotrigine

64
Q

Co-administration with valproate can double the plasma concentration of

A

Lamotrigine

65
Q

Co-administration with phenytoin or carbamazapine can reduce plasma concentrations of

A

Lamotrigine

66
Q

Was the most frequently used ASD for many years, but its use has declined considerably since the appearance of newer-generation ASDs with improved tolerability

A

Phenytoin

67
Q

Had the best balance of efficacy and tolerability in the large cooperative VA study that also included phenytoin phenobarbital, and primidone

-Became the standard treatment for focal seizures

A

Carbamazepine

68
Q

Remains the most effective ASD for idiopathic generalized epilepsy with generalized tonic-clonic seizures, and should remain a drug of first choice for men with generalized epilepsy

A

Valproate

69
Q

An important first-line ASD for focal seizures and generalized tonic-clonic seizures, although it is not FDA approved for initial monotherapy (only conversion-to-monotherapy)

A

Lamtrigotine

70
Q

Less sedating and has fewer cognitive adverse effects than traditional ASDs

A

Lamtrigotine

71
Q

ASDs that inhibit voltage gated Ca2+ channels do so by inhibiting the

A

T-type Ca2+ channels

72
Q

T-type channel inhibitors reduce the pacemaker current that underlies the

A

Thalamic rythm in spikes and waves seen in generalized absence seizures

73
Q

Specifically used for absence seizures

-Inhibits T-type Ca2+ currents

A

Ethosuximide (Zarontin)

74
Q

Has the adverse effects of leukopenia, thrombocytopenia, pancytopenia, and aplastic anemia

A

Ethosuximide (Zarontin)

75
Q

Activation of the GABAA receptor inhibits the postsynaptic cell by increasing the inflow of

-Will hyperpolarize the neuron

A

Cl- ions into the cell

76
Q

Enhance GABAA receptor–mediated inhibition of action potential by enhancing inflow of Cl–

A

Benzodiazepines and barbiturates

77
Q

Used for virtually every seizure type, especially when attacks are difficult to control

-The oldest of the currently available antiseizure drugs

A

Phenobarbital

78
Q

Used to treat status epilepticus

A

Phenobarbital

79
Q

Binds to GABAA receptor, prolonging the opening of the

A

Chloride channels

80
Q

Also reproted to inhibit glutamate release, enhance GABA transmission, and inhibit Na+ and Ca2+ conductance

A

Phenobarbital

81
Q

Is metabolized to phenobarbital in the body

A

Primidone

82
Q

Phenobarbital is metabolized by

A

Hepatic Microsomal Enzymes (CYP)

83
Q

Drugs metabolized by hepatic enzymes (e.g. oral contraceptives ) can be more rapidly degraded when co-administered with

A

Phenobarbital

84
Q

What are 4 major side effects of phenobarbital?

A

Sedation, Cognitive impairment, Hyperactivity in children, and CNS depression

85
Q

The ASD of choice for generalized absence seizures

A

Ethosuximide

86
Q

Are typically used as adjunctive therapy and have limited data to support monotherapy use

A

Benzodiazapines

87
Q

What are the two GABA analogs?

A

Tiagabine and Vigabatrine

88
Q

Functions by Inhibition of GABA transporter (GAT-1)

A

Tiagabine (Gabitril)

89
Q

Reduces reuptake of GABA by neurons and glial cells

A

Tiagabine (Gabitril)

90
Q

Inhibits the breakdown of GABA by targeting the enzyme GABA transaminase (GABA-T)

A

Vigabatrin (Sabril)

91
Q

Only available through a restricted distribution program due to concerns about retinal toxicity and permanent visual field loss

A

Vigabatrin (Sabril)

92
Q

Selective inhibitors of voltage-gated Ca2+ channels containing the α2δ1 subunit

-Originally designed to be GABA analogs

A

Gabapentin and Pregabalin

93
Q

What are the two main adverse effects of Gabapentin (neurontin) and Pregabalin (Lyrica)?

A

Weight gain and Somnolence

94
Q

Effective as a monotherapy, but can exacerbate myoclonic and absence seizures

A

Gabapentin

95
Q

Not effective for absence, myoclonic, or primary generalized tonic-clonic seizures

-Also used to treat Fibromyalgia

A

Pregabalin (Lyrica)

NBB Test 2 (33 decks)

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