Pharmacotherapy of Seizure Disorders Flashcards

1
Q

Epilepsy drugs

Used for…/mechanism

phenytoin

Partial/Generalized/Mech

A

Partial:
Simple +
Complex +

Generalized:
Tonic-clonic: 1st line
Absence:
Status: 1st line for propylaxis

Mech: ↑Na channel inactivation

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

Epilepsy drugs

Used for…/mechanism

Carbamazepine

Partial/Generalized/Mech
Also used for…
Causes:

A

Partial
Simple: 1st line
Complex: 1st line

Generalized
Tonic-clonic: 1st line (with phenytoin)
Absence:

Also used for…
1st line for trigeminal neuralgia

Mech: ↑Na channel inactivation

Causes agranulocytosis

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

Epilepsy drugs

Used for…/mechanism

Lamotrogine

Partial/Generalized/Mech

A

Partial
Simple: +
Complex: +

Generalized
Tonic-clonic: +
Absence:
Status:

Mech: Blocks voltage gated Na channels

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

Epilepsy drugs

Used for…/mechanism

Gabapentin

Partial/Generalized/Mech
Also used for….

A

Partial
Simple: +
Complex: +

Generalized
Tonic-clonic: +
Absence:

Also used for….
Also used for peripheral neuropathy, bipolar disorder

Mech: Designed as GABA analog but primarily inhibits HVA Ca channels

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

Epilepsy drugs

Used for…/mechanism

Topiramate

Partial/Generalized/Mech

A

Partial
Simple: +
Complex: +

Generalized
Tonic-clonic: +
Absence:
Status:

Mech: Blocks Na channels,
↑ GABA action

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

Epilepsy drugs

Used for…/mechanism

Phenobarbital

Partial/Generalized/Mech

A

Partial
Simple: +
Complex: +

Generalized
Tonic-clonic: +
Absence:
Status: 1st line in pregnant women, children

Mech: ↑ GABAA action

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

Epilepsy drugs

Used for…/mechanism

Valproic Acid

Partial/Generalized/Mech

A

Partial:
Simple: +
Complex: +

Generalized:
Tonic-clonic: 1st line
Absence: +
Status: Also used for myoclonic seizures

Mech:
↑ Na channel inactivation
↑ GABA concentration

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

Epilepsy drugs

Used for…/mechanism

Ethosuximide

Partial/Generalized/Mech

A

Partial:
Simple
Complex

Generalized:
Tonic-clonic
Absence: 1st line
Status

Mech:
Blocks thalamic T-Type Ca channels

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

Epilepsy drugs

Used for…/mechanism

Benzodiazepines

Partial/Generalized/Mech

A

Partial
Simple
Complex

Generalized
Tonic-clonic
Absence
Status: 1st line for acute
also used for seizures of eclampsia (1st line is MgSO4)

Mech: ↑ GABAA action

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

Epilepsy drugs

Used for…/mechanism

Tiagabine

Partial/Generalized/Mech

A

Partial:
Simple: +
Complex: +

Generalized:
Tonic-clonic
Absence
Status

Mech: Inhibits GABA reuptake

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

Epilepsy drugs

Used for…/mechanism

Vigabatrin

A

Partial
Simple: +
Complex: +

Generalized:
Tonic-clonic
Absence
Status

Mech:
Irreversibly inhibits GABA transaminase → ↑ GABA

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

Epilepsy drugs

Used for…/mechanism

Levetiracetam

A

Partial:
Simple: +
Complex: +

Generalized:
Tonic-clonic: +
Absence
Status

Mech:
Unknown, may modulate GABA and glutamate release

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

Partial seizures

1st line drugs

A

Simple: carbamazepine

Complex: Carbamazepine

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

Generalized seizures

1st line drugs

A

Tonic Clonic: Phenytoin, carbamazepine

Absence: Ethosuximide

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

1st line for acute seizures/prophylaxis

A

Acute: benzodiazepines

Proph: Phenytoin

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

Epilepsy drug toxicities

benzos

A

Sedation

Tolerance

Dependence

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

Epilepsy drug toxicities

carbamazepine

A
Diplopia, 
ataxia, 
blood dyscrasias (agranulocytosis, aplastic anemia)
liver toxicity
teratogenesis
induction of cytochrome P450
SIADH
Steven-johnson syndrome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Epilepsy drug toxicities

Ethosuximide

A
GI distress
Fatigue
Headache
Urticaria
Steven Johnson syndrome

EFGH – ethosuximide, fatigue, GI, Headache

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

Epilepsy drug toxicities

Phenobarbital

A

Sedation
Tolerance
Dependence
Induction of cytochrome P450

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

Epilepsy drug toxicities

Phenytoin

A
Nystagmus
Diplopia
Ataxia
Sedation
Gingival hyperplasia
Hirsutism
Megaloblastic anemia
Teratogenesis (fetal hydantoin syndrome)
SLE-like syndrome
Induction of P450
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Epilepsy drug toxicities

Valproic Acid

A

GI distress
Rare but fatal hepatotoxicity (measure LFTs)
Neural tube defects in fetus (spinal bifida)
Tremor
Weight gain
Contraindicated in pregnancy

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

Epilepsy drug toxicities

Lamotrigine

A

Steven-Johnson syndrome

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

Epilepsy drug toxicities

Gabapentin

A

Sedation

Ataxia

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

Epilepsy drug toxicities

Topiramate

A

Sedation
Mental Dulling
Kidney Stones
Weight Loss

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Stevens-Johnson syndrome

A

Prodrome of malaise and fever followed by rapid onset of erythematous/purpuric macules (oral, ocular, genital)

Skin lesions progress to epidermal necrosis and sloughing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Phenytoin

Mech/clinical use/toxicity

A

Mech
Use-dependent blockade of Na channels; ↑ refractory period; inhibition of glutamate release from excitatory presynaptic neuron

Clinical Use
Tonic clonic seizures
Also a class IB antiarrhythmic

Toxicity
Nystagmus
Ataxia
Diplopia
Sedation
SLE-like syndrome
Induction of cytochrome P450
Chronic use produces gingival hyperplasia in children, peripheral neuropathy, hirsutism, megaloblastic anemia (↓ folate absorption). Teratogenic (fetal hydantoin syndrome)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Barbiturates

Mech/clinical use/toxicity

A

Phenobarbital, pentobarbital, thiopental, secobarbital

Mech
Facilitate GABA A action by ↑ duration of CL- channel opening, thus ↓ neuron firing

Clinical Use
Sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental)

Toxicity
Dependence, additive CNS depression effects with alcohol, respiratory or CV depression (can lead to death)
DDI owing to induction of liver P450 enzymes
Treat overdose with sx management (assist respiration, ↑ BP)
Contraindicated in porphyria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Benzos

Mech/clinical use/toxicity

A

Diazepam, Lorazepam, Triazolam, Temazepam, oxazepam, midazolam, chlordiazepoxide, alprazolam

Mech
Facilitate GABA A action by ↑ frequency of Cl channel opening
↓ REM sleep
most have long half-lives and active metabolites

Clinical Use
Anxiety
Spasticity
Status epilepticus (lorazepam and diazepam)
Detox (esp alcohol – DT’s)
Night terrors
Sleepwalking
General anesthetic (amnesia, muscle relaxant)
Hypnotic (insomnia)

Toxicity
Dependence, additive CNS depression effects with alcohol. Less risk of respiratory depression and coma than with barbiturates
Tx overdose with flumazenil (competitive antagonist at GABA benzo rec)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Benzodiazepines

Short acting/most addictive

A

Short acting = TOM

Triazolam
Oxazepam
Midazolam

Also the highest addictive potential

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

GABA(A)-R

What binds to it

A

Benzos
Barbs
EtOH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

AED

MOA

Benzos

A

Enhance GABA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

AED

MOA

CBZ

A

Modulate Na channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

AED

MOA

Ethosuximide

A

Modulate Ca Channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

AED

MOA

felbamate

A

Enhance GABA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

AED

MOA

Gabapentin

A

Modulate Ca Channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

AED

MOA

Lamotrigine

A

Modulate Na Channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

AED

MOA

Levetiracetam

A

Unknown

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

AED

MOA

Oxcarbazepine

A

Modulate Na channels

39
Q

AED

MOA

Phenobarbital

A

Enhance GABA

40
Q

AED

MOA

phenytoin

A

modulate Na Channels

41
Q

AED

MOA

pregabalin

A

modulate Ca channels

42
Q

AED

MOA

tiagabine

A

Enhance GABA

43
Q

AED

MOA

Topiramate

A

Module Na channels
Enhance GABA
Inhibit excitatory NTs

44
Q

AED

MOA

Valproate

A

Modulate Na channels
Modulate Ca channels
Enhance GABA

45
Q

AED

MOA

Zonisamide

A

Modulate Na channels

Modulate Ca channels

46
Q

Therapeutic targets by seizure type

Partial seizures

A

 Focal but can become generalized

 Effective drugs limit sustained repetitive discharges

47
Q

Therapeutic targets by seizure type

Generalized seizures

A

 May have brief impairment or loss of consciousness

 Effective drugs reduce T-type Ca++ conductance

48
Q

Therapeutic targets by seizure type

Generalized tonic-clonic

A

Tonic spasm followed by synchronous clonic jerking

Effective drugs limit sustained repetitive discharges

49
Q

AED drug selection

Partial with or w/o generalization

1st line/2nd line/other drugs to consider/drugs to avoid

A
1st line:
CBZ
Oxcarbazepine
Valproate
Lamotrigine
Phenytoin
2nd line:
Topiramate
Phenobarbital
Levetiracetam (A)
Zonisamide (A)
Pregabalin (A)
Gabapentin (A)
Tiagabine (A)

Other drugs to consider:
Felbamate (R)
acetazolamide

Drugs to avoid: None

50
Q

AED drug selection

Generalized tonic-clonic

1st line/2nd line/other drugs to consider/drugs to avoid

A
1st line:
CBZ
Oxcarbazepine
Valproic Acid
Lamotrigine
Phenytoin

2nd line:
Topiramate
Levetiracetam (A)
Zonisamide (A)

Other drugs to consider:
Phenobarbital
acetazolamide

Drugs to avoid: Tiagabine

51
Q

AED drug selection

Absence

1st line/2nd line/other drugs to consider/drugs to avoid

A

1st line:
Ethosuximide
Lamotrigine
Valproate

2nd line:
Topiramate
Clonazepam

Other drugs to consider:
Levitiracetam

Drugs to avoid (could worsen seizure):
CBZ
Oxcarbazepine
Gabapentin
Tiagabine
phenytoin
52
Q

AED drug selection

Myoclonic

1st line/2nd line/other drugs to consider/drugs to avoid

A

1st line:
Valproate
Topiramate

2nd line:
Clonazepam
Lamotrigine
Levetiracetam
Zonisamide (A)

Other drugs to consider:
Felbamate

Drugs to avoid:
CBZ
Oxcarbazepine
Gabapentin
Tiagabine
pregabalin
53
Q

AED drug selection

atonic

1st line/2nd line/other drugs to consider/drugs to avoid

A

1st line:
Valproate
Lamotrigine

2nd line:
Clonzazepam
Topiramate
Zonisamide

Other drugs to consider:
Levetiracetam
Felbamate
Phenobarbital

Drugs to avoid:
CBZ
Oxcarbazepine
phenytoin

54
Q

AED drug selection

tonic

1st line/2nd line/other drugs to consider/drugs to avoid

A

1st line:
Lamotrigine
Valproate

2nd line:
Clonazepam
Topiramate

Other drugs to consider:
Levetiracetam
Zonisamide
Phenobarbital
Phenytoin
Acetazolamide
Felbamate (R)

Drugs to avoid:
CBZ
oxcarbazine

55
Q

AED drug selection

Lennox-Gastaut

1st line/2nd line/other drugs to consider/drugs to avoid

A

1st line:
Valproate

2nd line:
Topiramate
Lamotrigine
Zonisamide (A)

Other drugs to consider:
Felbamate

Drugs to avoid: None

56
Q

AED drug selection

Infantile spasms

1st line/2nd line/other drugs to consider/drugs to avoid

A

1st line:
ACTH
Corticosteroids

2nd line:
Clonazepam
Valproate

Other drugs to consider: None
Drugs to avoid: None

57
Q

AED drug selection

febrile

1st line/2nd line/other drugs to consider/drugs to avoid

A

1st line:
Phenobarbital
Valproate

2nd line: None

Other drugs to consider: none

Drugs to avoid:
Phenytoin
CBZ

58
Q

AED drug selection

Neonatal seizures

1st line/2nd line/other drugs to consider/drugs to avoid

A

1st line: Phenobarbital
2nd line: Phenytoin

Other drugs to consider: None
Drugs to avoid: None

59
Q

Pharmacokinetics of anti-epileptic drugs

Serum concentration monitoring

A

 Used primarily as a guide to direct therapy
 Useful in optimizing AED therapy, teasing out drug interactions, detecting noncompliance, and during pregnancy
 Important to consider that individual patients determine their “therapeutic” and “toxic” concentrations
 AED serum concentrations are not monitored with newer agents

60
Q

Pharmacokinetics of anti-epileptic drugs

Important considerations

phenytoin

A

 Phenytoin undergoes capacity-limited metabolism (elimination NOT proportional to serum concentration) and the capacity is reached at therapeutic concentrations

 Phenytoin is highly protein bound to albumin (90%). The “free” phenytoin concentration (unbound) is a more accurate description of the therapeutic effects of this drug. Thus, changes in protein binding in certain disease states (renal or hepatic disease, burns, etc.) can effect the free concentration and the effect of the drug.

61
Q

Pharmacokinetics of anti-epileptic drugs

Important considerations

CBZ

A

Carbamazepine undergoes “autoinduction” whereby it induces its own metabolism such that concentrations may be initially “therapeutic” only to be reduced once autoinduction occurs. This process begins within the 1st week after starting therapy and plateus at 2-3 weeks.

62
Q

Figure out if you need to know chart on

pg. 481

A

Do it

63
Q

Pharmacokinetics of agents in status epilepticus

Onset of action/half-life/duration

diazepam

A

Onset of action
Half life
Duration of anti-seizure effect

0.5-2 min
24-57 hr
10-20min

Highly lipophilic; may be given rectally

64
Q

Pharmacokinetics of agents in status epilepticus

Onset of action/half-life/duration

lorazepam

A

Onset of action
Half life
Duration of anti-seizure effect

2-3 min
8-25 hr
~6hr

DOC in SE – longer duration vs diazepam

65
Q

Pharmacokinetics of agents in status epilepticus

Onset of action/half-life/duration

midazolam

A

Onset of action
Half life
Duration of anti-seizure effect

<5 min
1.5-4hr
5-10min

66
Q

Pharmacokinetics of agents in status epilepticus

Onset of action/half-life/duration

Phenytoin

A

Onset of action
Half life
Duration of anti-seizure effect

15min
IV: 10-15hr
Similar to ½ life

67
Q

Pharmacokinetics of agents in status epilepticus

Onset of action/half-life/duration

fosphenytoin

A

Onset of action
Half life
Duration of anti-seizure effect

10-30min
IV: 10-15hr
Similar to ½ life

68
Q

Induction

Def/AED major inducers

A

Induction = increased synthesis of drug metabolizing isoenzymes in the liver resulting in an increase in the rate of metabolism of drugs that are substrates of those enzymes and thus the plasma concentration of those drug is decreased. If the affected drug has an active metabolite, induction can result in increased metabolite concentration and possibly an increase in drug toxicity. The time course of induction is dependent on the rate of enzyme synthesis and degradation and the time to reach steady state concentrations of the inducing drug. Thus the time course is generally gradual and dose-dependent.
AED MAJOR INDUCERS: CARBAMAZEPINE, PHENYTOIN, PHENOBARBITAL, FELBAMATE

69
Q

Inhibition

Def/AED major inhibitors

A

Inhibition = drug or its metabolite blocks the activity of one or more drug metabolizing enzymes, resulting in a decrease in the rate of metabolism of the affected drug and thus higher plasma concentrations. Inhibition is competitive & dose-dependent and begins as soon as sufficient concentrations of the inhibitor are achieved. (can be seen within 24 hour of inhibitor administration)

AED MAJOR INHIBITORS: VALPROIC ACID

70
Q

Figure out if you have to know charts on pg. 483

A

Do it

71
Q

AED

Lab tests

A

Baseline (i.e. prior to starting therapy) lab tests should include liver function tests (SGOT, SGPT, alkaline phosphatase), serum albumin, complete blood cell count with differential, urinalysis, serum creatinine (for renally eliminated drugs) and serum electrolytes. Additionally for carbamazepine should obtain baseline urinalysis and serum sodium; and for valproic acid obtain baseline serum ammonia.

In otherwise healthy and asymptomatic patients, routine laboratory monitoring after starting therapy is unnecessary with clinical laboratory tests only being repeated if indicated by the patient’s clinical condition. For patients with abnormal baseline laboratory tests, further workup is required to evaluate their cause and follow-up monitoring performed as indicated.

72
Q

Phenytoin

Adverse drug rxns

Conc related/idiosyncratic/pregnancy category

A
Conc-related:
Ataxia
Diplopia
Nystagmus
Sedation
Drowsiness
Idiosyncratic:
Acne
Gum Hypertrophy
Hirsutism
Megaloblastic anemia
Rash
Lupus-like syndrome
Behavior changes
Metabolic bone disease
Intellectual blunting
Pregnancy category:
D
-Fetal hydantoin syndrome
-cleft lip and palate
-mental retardation
-low set ears
-skeletal spinal abnormalities
-heart malformation
73
Q

Phenobarbital

Adverse drug rxns

Conc related/idiosyncratic/pregnancy category

A

Conc-related:
Sedation
Drowsiness
Ataxia

Idiosyncratic:
Rash 
cognitive impairment
Hyperactivity
ADD
Passive-aggressive
Behavior (mood change)
Intellectual blunting

Pregnancy category:
D

74
Q

CBZ

Adverse drug rxns

Conc related/idiosyncratic/pregnancy category

A

Conc-related:
Diplopia
Nausea
Drowsiness

Idiosyncratic:
Hyponatremia
Leukopenia
Aplastic anemia
Rash
Pregnancy category:
D
-neural tube defects
-minor craniofacial defects
nail hypoplasia
75
Q

Valproate

Adverse drug rxns

Conc related/idiosyncratic/pregnancy category

A
Conc-related:
GI upset
Sedation
Unsteadiness
Thrombocytopenia
Tremor
Idiosyncratic:
Acute hepatic failure
Acute pancreatitis
Alopecia
Weight gain
Hyperammonemia
Pregnancy category:
D
-neural tube defects
-fetal valproate syndrome (developmental delays, limb and digit abnormalities)
-black box warning in pregnancy
76
Q

Ethosuximide

Adverse drug rxns

Conc related/idiosyncratic/pregnancy category

A

Conc-related:
GI upset
Drowsiness
Dizziness

Idiosyncratic:
Hiccups
Blood dyscrasias
Headache

Pregnancy category:
C

77
Q

Felbamate

Adverse drug rxns

Conc related/idiosyncratic/pregnancy category

A

Conc-related:
GI upset
Insomnia
Anorexia

Idiosyncratic:
Aplastic anemia
Hepatotoxicity
Weight loss

Pregnancy category: C

78
Q

Gabapentin

Adverse drug rxns

Conc related/idiosyncratic/pregnancy category

A

Conc-related:
Sedation
Drowsiness
Ataxia

Idiosyncratic:
Weight gain
Aggressive behavior
Pedal edema

Pregnancy category: C

79
Q

Lamotrigine

Adverse drug rxns

Conc related/idiosyncratic/pregnancy category

A

Conc-related:
Insomnia
Ataxia
Diplopia

Idiosyncratic:
Rash
Headache

Pregnancy category: C

80
Q

Topiramate

Adverse drug rxns

Conc related/idiosyncratic/pregnancy category

A
Conc-related:
Slowed thinking
Psychomotor slowing
Speech/language problems
Drowsiness
Ataxia
Dizziness
Idiosyncratic:
Renal calculi
Weight loss
Glaucoma
Paresthesia
Metabolic acidosis

Pregnancy category:
C

81
Q

Oxcarbazepine

Adverse drug rxns

Conc related/idiosyncratic/pregnancy category

A

Conc-related:Somnolence
Dizziness
Diplopia
Nausea

Idiosyncratic:
Hyponatremia
Rash

Pregnancy category: C

82
Q

Tiagabine

Adverse drug rxns

Conc related/idiosyncratic/pregnancy category

A
Conc-related:
Dizziness
Somnolence
Blurred vision
Depression
Weakness
Irritability
Slowed thinking

Idiosyncratic:
Non-convulsive status
Mood instability

Pregnancy category: C

83
Q

Zonisamide

Adverse drug rxns

Conc related/idiosyncratic/pregnancy category

A
Conc-related:
Sedation
Dizziness
Cognitive impairment
GI upset
Idiosyncratic:
Rash
Weight loss
Kidney stones
Hypohidrosis

Pregnancy category: C

84
Q

Levetiracetam

Adverse drug rxns

Conc related/idiosyncratic/pregnancy category

A

Conc-related:
Somnolence
Dizziness

Idiosyncratic:
Depression
Aggression
Infection

Pregnancy category: C

85
Q

Pregabalin

Adverse drug rxns

Conc related/idiosyncratic/pregnancy category

A

Conc-related:
Somnolence
Dizziness
Blurred vision

Idiosyncratic:
Weight gain
Peripheral edema
Increased CK
Decreased platelet count

Pregnancy category: C

86
Q

Concerns of long-term AED administration

Bone disorders

A

Bone Disorders: Bone disorders particularly osteoporosis have been associated with AEDs. Bone mineral density decreases leading to osteoporosis and fractures have been associated with some AEDS (phenobarbital, phenytoin, carbamazepine and valproate) in both women and men. The newer AEDs have not been systematically evaluated for these relationships. Potential mechanisms of osteoporosis development include increased catabolism of vitamin D, impairment of calcium absorption, impaired bone resorption and formation, hyperparathyroidism, vitamin K deficiency, and calcitonin deficiency. Osteoporosis is of particular concern in patients with epilepsy because of the increased risk of fractures during seizures. Experts recommend bone density testing every 5 years during AED treatment in men and premenopausal women and before AED initiation in postmenopausal women. Treatment with vitamin D at doses of 400-4000IU/day, calcium supplementation, bisphosphonates, or calcitonin may be necessary.

87
Q

Concerns of long-term AED administration

Intellectual function

A

Recent studies have demonstrated that significant interference with higher cognitive functions; including attention span, concentrating ability, memory, information processing, motor speed and IQ; occurs during AED therapy

88
Q

Concerns of long-term AED administration

cognition

A

Based on published data from prospective, chronic dosing studies, phenobarbital and topiramate have the highest potential for causing cognitive dysfunction. AEDs with traditional gamma-aminobutyric acid (GABA)ergic mechanisms have the most detrimental effects on cognitive function, possibly because they impair attention. A number of consistent risk factors have been established. Polypharmacy and high blood levels of an antiepileptic drug (AED) increase the risk of cognitive side effects.

89
Q

Concerns of long-term AED administration

memory

A

Impaired memory is among the most common complaints of patients with epilepsy. Multiple factors contribute to memory impairment in patients with epilepsy.

90
Q

AED therapy in pregnancy

AAN rec

A

Sex hormone fluctuations during maturation may exacerbate seizures at particular points during the life of women, eg. during menarche, menses, pregnancy, or later in the perimeno- pausal years.

American Academy of Neurology recommends monotherapy during reproductive years. There is a teratogenic potential of anti epileptic drugs. Ideally, in well-controlled seizures, taper and discontinue anti epileptic drugs before conception. Risk of continuing must be weighed against the benefits. Post partum adjustment of the anti epileptic drugs dose will be necessary if the dose was increased during pregnancy, and usually can be reduced by eight weeks after delivery. All women of child bearing years should receive folate supplementation (at leaset 1 mg/day) before and during the pregnancy.

91
Q

AED

In-utero effects

A

In utero exposure to antiepileptic drugs (AEDs) can cause intrauterine growth retardation, congenital malformations, and cognitive dysfunction. The most common major malformations are cleft lip/palate, heart defects, neural tube defects, and urogenital defects. Current treatment guidelines advise use of AED monotherapy and folate supplementation beginning before and continuing throughout pregnancy. Prenatal screening for major malformations should be offered.

92
Q

AED

Safety while breast feeding

A

Safety while breast-feeding is a common concern. Authorities recommend that it is safe with no risk of hematological or hepatotoxicity, although some sedation may occur with phenytoin, carbamazepine and phenobarbital. The efficacy of birth control pills is decreased by the use of enzyme-inducing anticonvulsants. Some prescribe estrogen/progesterone pill with higher hormonal doses or an alternative and preferred approach, is to use a second method of contraception.

93
Q

AEDs that decrease effectiveness of oral contraceptives

A
CBZ
Felbamate
Oxcarbazepine
Phenobarbital
Phenytoin
Primidone
Topiramate (doses >200mg/day)
94
Q

AEDs that do not decrease the effectiveness of oral contraceptives

A
Benzodiazepines
Gabapentin
Lamotrigine
Levetiracetam
Tiagabine
Valproate
Zonisamide