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Pharmacology Test 3 > AEDs > Flashcards

AEDs Flashcards

1
Q

Monotherapy is often imitated and preferred with about ______ % of patients considered to be well controlled, meaning what?

A

65%
Seizure freedom or at least seizure reduction

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2
Q

List the 4 factors indicative of a successful withdrawal of AEDs

A

Pt. Seizure free for 2-4 years
Pt. Who achieve complete seizure control within one year
Pt. Whose seizure onset occurred at either older than 2 years of age or younger than 35 years of age
Pt. Who have a normal EEG and neurological examination

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3
Q

If the decision is made to stop AEDs, drug therapy should be discontinued how?

A

Gradually to avoid seizure relapse

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4
Q

Sudden withdrawal of an AED can result in what?

A

Increase in seizure frequency or status epilepticus

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5
Q

Seizure recurrence typically occurs within the first _____ to _______ of AED withdrawal

A

6 to 12 months

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6
Q

Poor prognostic indicators suggesting the need for lifelong AED therapy are:

A

High seizure frequency
Repeated status epilepticus episodes
Combination of seizure types
Development of abnormal mental functioning

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7
Q

The prognosis of needing lifelong AED therapy may depend on the underlying?

A

Epilepsy syndrome

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8
Q

What is the only medication needed to treat absence seizures?

A

Ethosuximide

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9
Q

Neurologist may use an unapproved medication to treat a seizure based on what?

A

The individual characteristics of the patient such as: side effect profile, family history, mechanism of action

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10
Q

What two things commonly dictate initial choice in therapy?

A

Adverse effects profile and comorbid health conditions

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11
Q

Benzodiazepines are what class of anticonvulsants?

A

GABAergic AEDs

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12
Q

List some Benzodiazepines used as AEDs?

A

Remember C3DML
Three class daily makes you Loony
Clonazepam
Clorazepate
Clobazam
Diazepam
Midazolam
Lorazepam

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13
Q

Broad range of duration of action from _____ hours for diazepam, and up to ____ hours for lorazepam.

A

2 hour
72 hours

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14
Q

What medication was approved as a nasal spray intended. For rescue in patients experiencing prolonged seizures, recently approved by the FDA?

A

Midazolam

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15
Q

Benzodiazepines are used for ________ management or prevention of seizures and are not used for ________ management.

A

Short-term management
Long term maintenance

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16
Q

Benzodiazepines augment the action of _________ channels, which results in what?

A

GABA-A channels,
Hyper polarized neurons and account for an increased chloride ion conductance

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17
Q

Diazepam can be administered what routes?

A

Rectal gel
IM
IV (tx of status epilepticus)

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18
Q

The duration of action of diazepam is prolonged why?

A

Due to its active metabolite

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19
Q

Repeated dosing of the Diazepam, can result in a half-life as long as?

A

100 hours
Making diazepam a long acting benzodiazepine when given regularly

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20
Q

Lorazepam is give what routes?

A

IV or IM treatment of status epilepticus

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21
Q

Lorazepam’ s duration of action compared to diazepam is ____________>

A

Much longer

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22
Q

Lorazepam does not distribute to __________ __________ as extensively as does diazepam, meaning what?

A

Fat deposit
Enjoys more extensive distribution, resulting in longer CNS exposure

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23
Q

Clobazam comes in what administrative routes?

A

Tablet or oral suspension

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24
Q

Clobazam is used as an adjuvant in the treatment of ?

A

Lenox Gustate Syndrome

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25
Q

What is the oldest of the current available AEDs?

A

Phenobarbital

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26
Q

Phenobarbital is a member of the class of drugs called?

A

Barbiturates

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27
Q

Barbiturates are divided into three classes based on their duration of action, which are?

A

Short acting
Intermediate acting
Long acting

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28
Q

Phenobarbital is a ______ acting barbiturate and currently the only one which is regularly used for AEDs.

A

Long

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29
Q

What is the mechanism of action for barbiturates is?

A

Binding to an allosteric regulatory site on the GABA-A receptor and enhancing the influx of chloride ions into the neurons through the GABA-A channel when GABA is bound to the receptor.

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30
Q

High concentrations of barbiturates that typically occur with overdoses, may cause _________ influx through the _________ receptor in the absence of _________.

A

Chloride
GABA-A receptors
GABA

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31
Q

Benzodiazepine require the presence of GABA in order to do what?

A

Cause chloride ion influx through the GABA-A receptor

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32
Q

Phenobarbital has a narrow therapeutic range, which is?

A

10 to 48 micrograms per milliliter

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33
Q

Pheno

A

K

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34
Q

Name a short acting barbiturate?

A

Pentobarbital

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35
Q

Are benzodiazepine or barbiturates more dangerous and have a higher risk of overdose? Why?

A

Barbiturates/because they do not require the presence of GABA in order to alter chloride ion influx through the GABA-A receptor.

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36
Q

Phenobarbital have the potential to be __________.

A

Abused

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37
Q

Phenobarbital has stronger ___________ effects than other AEDs.

A

Sedating

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38
Q

Phenobarbital has what effect on pediatric patients?

A

Paradoxical stimulation effect rather than sedation effect

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39
Q

Phenobarbital is discouraged in patients who have a history of?

A

Suicidal ideations

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40
Q

Phenobarbital is classified as pregnancy category _____

A

D- meaning positive evidence of human fetal risk

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41
Q

Vigabatrin was approved in 2009 as an adjuvant treatment of?

A

Refractory focal seizures which are accompanied by impaired awareness

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42
Q

Vigabatrin are available as both?

A

Tablets and powder packets for dissolution in liquid.

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43
Q

What is vigabatrin mechanism of action?

A

Inactivator of GABA-transaminase or GABA-T

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44
Q

Describe what mechanism based inactivators are?

A

Drugs which bind competitively to an enzyme’s active site to irreversibly inhibit it.

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45
Q

How can an mechanism based inactivator be overcome? How long does it take?

A

By producing more of the enzyme affected.
Takes a reasonably long amount of time

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46
Q

Inactivation of GABA-T results in prolonged synaptic concentrations of __________, since the primary metabolic pathway has been shut down.

A

GABA

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47
Q

Vigabatrin carries a black box warning regarding a risk of?
Particular concern in who?

A

Permanent irreversible vision loss, which is particularly a concern in children

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48
Q

Permanent irreversible vision loss with vigabatrin is dose __________ and visual field effects may occur in up to ____ of patients.

A

Independent
30%

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49
Q

Due to the risk of permanent irreversible vision loss with vigabatrin, the medication is only available through ______ program. Describe this program

A

REMS program

A Risk Evaluation and Mitigation Strategy (REMS) is a drug safety program that the U.S. Food and Drug Administration (FDA) can require for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks

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50
Q

Tiagabine is what class of drug?

A

GABA reuptake inhibitor

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51
Q

Describe the mechanism of action of tiababine?

A

Binds to and blocks the GABA reuptake channel GAT1

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52
Q

GABA reuptake channel GAT1 is also known as the?

A

GABA Transporter

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53
Q

Blocking the GAT1 from GABA prolongs what?

A

GABA in the synapse and therefore enhances the effect of GABA released by the GABAergic neurons.

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54
Q

Tiagabine adverse effect profile is ___________.

A

Mild, though it is not commonly used clinically.

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55
Q

VAlproate has the same mechanism of action as?

A

Valproate acid

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56
Q

What are the mechanisms of action for valproate and valproic acid?

A

Inhibiting succinct semi-aldehyde dehydrogenase,
The inhibition results in an increase in succinct semi-aldehyde, which inhibits GABA transaminase, ultimately reduces GABA metabolism and thus produces an increase in GABA nerve transmission

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57
Q

What are the black box warning for valproate and valproic acid?

A

Hepatic toxicity
Pancreatitis
Risk of liver failure in patients with mitochondrial disease
Teratogenicity

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58
Q

Valproate and valproic acid is considered to be pregnancy category ____.

A

D-evidence of harm to the fetus

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59
Q

Many AEDs suppress neuronal action potential generation by altering the influx of ions through?

A

Voltage gated channels

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60
Q

Name the most common two ion channels involved in AED pharmacology?

A

Sodium and calcium channels

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61
Q

Name three calcium channels found in the central nervous system?

A

L, N, and T calcium channels

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62
Q

AEDs that block T type calcium channels are often associated with efficacy in the management of ?

A

Absence seizures

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63
Q

Absent seizures are unique from other seizures in that they only involve the dysfunction of?

A

T type calcium channels

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64
Q

Most AEDs that have an anti-seizure effect due to the alteration of cation conductance action, act by?

A

Prolonging the inactivation of the sodium channels involved in the high frequency firing of neurons that occurs during a seizure.

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65
Q

After depolarization, voltage-gated sodium channels are blocked by an ____________ which allows depolarization to occur, leading to a subsequent action potential. This process is called ________________.

A

Inactivation gate
Inactivation

66
Q

If inactivation is prolonged, the neurons will not be able to do what?

A

Generate an action potential as fast and therefore not fire as rapidly producing an anti seizure effect.

67
Q

Carbamazepine has a narrow therapeutic range which is?

A

4 to 12 micrograms per milliliter for the management of seizures

68
Q

Carbamazepine Concentration related adverse effects are usually not seen until blood concentrations reach at least _____ micrograms per milliliter and increase in severity as?

A

8
Blood levels rise

69
Q

Neurotoxic effect of carbamazepine can be minimized by ?

A

Gradual increase in dose or adjustment of maintenance dosing

70
Q

Signs and symptoms of carbamazepine concentration at or higher 8-12 mcg/mL?

A

lethargy, drowsiness
Dizziness
Diplopia
Ataxia
Hyponatremia (related to SIADH)

71
Q

Signs and symptoms of carbamazepine at greater than 12 mcg/mL?

A

Convulsions
Respiratory depression
Coma

72
Q

Carbamazepine is associated with teratogenicity, placing it into the pregnancy category _____.

A

D

73
Q

What are the two black box warnings for Carbamazepine?

A

Aplastic anemia, including agranulocytosis.
A high risk of life threatening rash, also known as toxic epidermal necrolysis and Steven Johnson syndrome.

74
Q

The risk of a rash in carbamazepine is up to ___ times higher risk in patients of _______ decent who have a specific allele,
_____________.

A

10
Asian
HLA B

75
Q

HLA B variant occurs in approximately _____% of the Asian population.

A

15

76
Q

Patients should be tested for _______ before being placed on carbamazepine

A

HLA B

77
Q

Phenytoin causes pain upon?

A

Injection

78
Q

IV formulation (Phenytoin/Fosphentoin) carries a black box warning that infusion rate must NOT exceed? Due to?

A

50 milligrams per minute due to toxicity

79
Q

Phenytoin toxicity can cause severe ________ and ________.

A

Hypotension and cardiac arrhythmias

80
Q

Most patients should have a lower rate of IV infusion of phenytoin such as _________ mg per minute to minimize infusion related adverse effects

A

10 to 20

81
Q

What was created based on the complications of IV administration of phenytoin?

A

Fosphenytoin

82
Q

Fosphenytoin is what kind of drug __________ (when is it active)

A

Prodrug (not active till it is metabolized).

83
Q

Fosphenytoin is a __________ molecule that is rapidly converted to _______ upon administration.

A

Water soluble
Phenytoin

84
Q

Both phenytoin and fosphentoin can cause a dangerous skin condition called? If administered how?

A

Purple club syndrome
IV infusion

85
Q

Phenytoin is a delicate drug to dose because it has a?

A

Narrow therapeutic range

86
Q

Phenytoin blood levels should be frequently monitored during?

A

Invitation of therapy and periodically checked thereafter

87
Q

What oral effects can phenytoin cause? What percentage of patients have some degree of this upon therapy with this medication?

A

Gingival hyperplasia
20%

88
Q

What other dose effects can phenytoin cause beside purple club syndrome or gingival hyperplasia?

A

Nystagmus - involuntary rhythmic side-to-side, up and down or circular motion of the eyes
&
Hirsutism

89
Q

Phenytoin is bound to ________ in the blood, which ______ its efficacy. Why?

A

Albumin
Reduces
Because the bound drug cannot interact with voltage gated sodium channels to reduce seizure activity

90
Q

What happens to a patient with hypoalbuminemia on phenytoin?

A

There is less albumin for phenytoin to become bound to and thus a higher concentration of free drug is available.

91
Q

A patient with hypoalbuminemia on phenytoin may have the same drug level as a patient with normal albumin levels but what should you know?

A

Because they have more free drug in there system, because there is less albumin for the phenytoin to bind to, the patient will have a greater therapeutic effect/possibly toxic effect.

92
Q

Phenytoin is teratogenic and is categorized as pregnancy category ____.

A

D

93
Q

Lamotrigine’s mechanism of action is?

A

Lamotrigine binds to sodium channels, and prolongs their inactivation, decreasing high frequency neuronal firing

94
Q

What suggest that lamotrigine has additional mechanisms of actions?

A

Lamotrigine works on a broader spectrum of seizures than carbamazepine or phenytoin which both bind to sodium channels prolonging their inactivation

95
Q

What other mechanism’s of action does lamotrigine have besides binding to sodium channels and prolonging their inactivation?

A

Studies indicate that this medication inhibits the release of glutamate and reduces the low threshold calcium ion currents seen in absent seizures

96
Q

Lamotrigine is well tolerated besides the risk of?

A

Steven Johnson Syndrome

97
Q

When does the Steven Johnson syndrome rash start with patients on lamotrigine?

A

Rash generally occurs 2 to 8 weeks after starting or restarting therapy with this medication.

98
Q

Describe dose titrations of lamotrigine? What is the reasoning?

A

dosing is titrated every 2 weeks
to minimize the risk of rash.

99
Q

A new warning was issued for lamotrigine, which resolves after the medication is discontinued. What is it?

A

Aseptic Meningitis

100
Q

What is the indication for Ethosuximide?

A

Treating absence seizures

101
Q

What is the mechanism of action for ethosuximide?

A

Reduces low threshold calcium ion currents, presumably by interacting in some manner with calcium channels

102
Q

What calcium currents are targeted with ethosuximide?

A

T type calcium currents in the thalamus

103
Q

Doses of ethosuximide are usually divided to minimize the risk of?

A

Gastrointestinal side effects

104
Q

List the adverse effects of Ethosuximide?

A

Depression
Aplastic anemia
Leukopenia
GI discomfort (Highest risk among AEDs)

105
Q

Gabapentin and pregablin does what with GABA receptors?

A

Neither drug interacts with GABA receptor

106
Q

What are the indications for gabapentin and pregablin?

A

Treatment of neuropathic pain and management of epilepsy

107
Q

Gabapentin and Pregabalin appear to have _________ effects and/or _________ effects on glutamate, but the degree to which these effects contribute to the anti-seizure activity is not clear

A

GABA-ergic
inhibitory

108
Q

Gabapentin increases brain _______ concentrations.

A

GABA

109
Q

Gabapentin and pregabalin bind to and block _______ channels inhibiting _______ release

A

N-type presynaptic calcium channels
glutamate

110
Q

Gabapentin is nearly 100% eliminated ______ as unchanged, meaning what? minimizing what?

A

renal
meaning it’s really not metabolized
minimizing risk for drug-drug interactions

111
Q

since the body is completely dependent on renal function for clearance of gabapentin, a decrease in renal functions will affect?

A

gabapentin pharmacokinetics

112
Q

the dose for gabapentin should be adjusted in patients with a creatinine-clearance of?

A

less than 60 millilters per minute

113
Q

Gabapentin is well tolerated with a milder adverse effect profile as compared to most AEDs. True or False

A

True

114
Q

what are common side effect of gabapentin?

A

sedation and weight gain

115
Q

Gabapentin and pregabalin both have an idiosyncratic reaction of?

A

peripheral edema

116
Q

pregabalin is ______ tolerated, but has modest _____ potential.

A

well
abuse

117
Q

what kind of diet offers a nonpharmacologic therapy option for individuals who suffer from seizures?

A

ketogenic

118
Q

ketogenic diet is used in patients with?

A

refractory epilepsy (particularly in children with Lennox Gastaut Syndrome).

119
Q

Initial states of fasting of ketogenic diet is usually performed where? followed by?

A

performed under medical supervision in a hospital, followed by a high fat, low carb diet.

120
Q

ketogenic diet mimics the metabolic effects of ______ and leads to ketoacidosis, a state that has ______ properties

A

starvation
anticonvulsant

121
Q

Long term effects of ketogenic diet is?

A

kidney stones
increased bone fractures
slowed growth or weight gain
constipation
dehydration
hypercholesterolemia

122
Q

what should be supplemented while adhering to the ketogenic diet?

A

vitamins and minerals

123
Q

Older AEDs have more drug to drug interactions involving?

A

CYP 450 metabolism

124
Q

Newer AEDs typically have fewer? but are significantly more?

A

adverse effects
expensive

125
Q

list three benefits of newer AEDs compared to older AEDs

A

improved adverse effect profile
little to no need for therapeutic drug monitoring
less risk for pharmacokinetic drug-to-drug interactions

126
Q

AEDs are give two adminstration routes commonly which are?

A

IV
oral

127
Q

AEDs are given IV for?

A

emergency management of seizures or for the prevention of seizures in hospitalized patients who cannot take oral medications

128
Q

The ideal IV AED would allow for what?

A

rapid administration of large doses for acute management of seizures.

129
Q

Oral AEDs are given for?

A

long term management of epilepsy

130
Q

the ideal oral delivery formulation would require what?

A

no more than once daily dosing and provide sustained blood levels of an AED that do not fluctuate greatly throughout the day

131
Q

A large fluctuation in blood levels for an AED medication may put the patient at risk for?

A

toxicity or lack of seizure protection

132
Q

some AEDs, particularly those with shorter half-lives are provided as _______ formulations. Why?

A

extended-release
to more closely achieve this ideal outcome

133
Q

clinically useful AEDs must be able to pass the

A

blood brain barrier

134
Q

if a potential AED drug that cannot cross the blood brain barrier meaning they cannot?

A

sufficiently into the CNS

135
Q

the pharmacological premise behind the mechanism of action for AED is?

A

suppression of abnormal and or regular neuron action to mitigate excessive potential generation or firing in the central nervous system nerve fibers.

136
Q

list the three general neuropharmacological mechanisms by which drugs decrease seizure activity?

A
  1. They can enhance inhibitory neurotransmission
  2. They can inhibit excitatory neurotransmission, usually by counteracting the effects of glutamate
  3. They can modify ion conduction involved in neuron action potential, usually by affecting voltage-gated sodium, potassium, or calcium channels
137
Q

Drugs that can increase the effect of GABA will theoretically have anti-seizure activity and possibly be useful for management of epilepsy?

A

inhibit glutamate
decrease sodium and calcium ion conductance

138
Q

all AEDs act on the central nervous system to exert their anti-seizure effects so all AEDs commonly caused dose related CNS side effects such as:

A

remembers CARBS
C - concentration
A - ataxia/dizzy
R - rash
B - behavior (suicide)
S - sleep

139
Q

excessive sleepiness are predictable in common with _____ dosing and may diminish adherence to therapy

A

initial

140
Q

difficulty in concentration that occurs soon after initial dosing may _____ improve over weeks of therapy

A

gradually

141
Q

Hypersensitivity to AEDs often begins as a rash, which patients can monitor themselves if?

A

counseled appropriately

142
Q

Therapeutic drug monitoring refers to?

A

refers to plasma level monitoring of a drug to ensure that the amount of drug in the body is not too low or too high.

143
Q

concentration at the site of action effects?

A

efficacy

144
Q

the risk of toxicity often but does not alway increase with the ?

A

amount of drug present in the body

145
Q

Therapeutic drug monitoring is generally preferred for drugs that have a ?

A

narrow therapeutic range and medication with known toxicity at elevated levels

146
Q

AEDs that have a narrow therapeutic range and these include?

A

Remember PVC Pipe is Narrow
P - Phenobarbital
V - Valproic Acid Level
C - Carbamazepine

Pipe-Phenytoin

147
Q

list the three goals of AED therapy?

A

complete elimination of seizures

no or minimal side effects of AEDs

optimal health related quality of life

148
Q

if the causes of seizures are identifiable, steps should be taken to correct the underlying cause if possible. list four possible causes

A

CNS tumor

infection

trauma

electrolyte imbalance

149
Q

management of epilepsy often require ________ AED therapy

A

lifelong

150
Q

A patient’s treatment plan with AED therapy must be individualized to seizure _____ and ______, with neurologist weighing benefits and risk of drug therapy with their patients

A

classifications and frequency

151
Q

factors that are important in the selection of AED treatment include: (7)

A

patient population efficacy

ease of administration with dosage form and schedule

medication cost

insurance coverage

adverse effect profile

drug interactions

therapeutic drug monitoring

152
Q

Any exisiting comorbidities such as shoudl also be managed according such as (3)

A

remember DAI cause seizures

D-depression

A-Anxiety

I-Insomnia

153
Q

Avoidance of _______ factors is necessary to minimize seizures

A

precipitating

154
Q

Medications that can do what should be avoided in eptileptic patients?

A

lower the seizure threshold

155
Q

AED therapy si initiated after ____ or more seizure episodes has occured.

A

two

156
Q

AED therapy may not be indicated in patients who seizures have ____ impact on their lives or a patient who?

A

minimal

has had one seizure

157
Q

Risk factors are weighed after the first seizure episode to determine the likelihood of recurrent seizures: Some factors include?

A

Remember its a “PHAGE of factors

P - Patient preference

H - Seizure History

A - Neuroanatomic defects

G - genetics (family history)

E - EEG patterns

158
Q

Prior to initating AED therapy an accurate diagnosis of seizure ____ and ____ is essential to select an appropriate initial AED

A

type and classification

159
Q

One of the common causes of seizure recurrence is failure to ?

A

diagnose epilepsy syndrome accurately

160
Q

patients must recieve adequate medication counseling on AED adverse effects to ensure?

A

medical adherence

161
Q

The main reason for treatment failure in medications is medication noncompliance in patients non adhering to ?

A

AED therapy

Pharmacology Test 3 (4 decks)

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