AEDs in special situation

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AEDs in special situation

• Dr. Thomas Iype
• Medical College
• Thiruvananthapuram

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Mentally challenged child
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Mentally challenged child

• Lamotrigine
• Oxcarbazepine

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Patients with psychiatric illness
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Psychiatric illness

• Avoided

• Preferred

• Levetiracetam
• Topiramate

• Lamotrigine

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Patients with allergic reaction to AEDs
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Allergic reaction

• Phenytoin,
• Carbamazepine,
• Oxcarbazepine,
• Phenobarbital,
• Primidone,
• Zonisamide,
• Lamotrigine

• Valproate,
• Gabapentin,
• Topiramate,
• Levetiracetam,
• Tiagabine.

• Aromatic antiepileptic drugs

• Alternate drugs

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Patients with obesity
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Obese

• Valproate
• Gabapentin

• Topiramate,
• Zonisamide

• Avoided

• Considered

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AEDs in patients on HAART or ATT
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AEDs in patients on HAART or ATT

• Non enzyme inducer AED

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AEDs in Porphyria
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Acute intermittent Porphyria

• AD Trait
• Partial deficiency of Porphobilinogen deaminase
• Accumulation of ALA PBG
• Watson-Schwartz test

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Acute intermittent Porphyria

• Treatment
• Haeme arginate
• Atleast 400g glucose each day
• Gabapentin or IV lorazepam

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Porphyria

• Reported to Exacerbate Disease
• Barbiturates
• Carbamazepine
• Fosphenytoin
• Phenytoin
• Primidone
• Valproic acid

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Porphyria

• Theoretically Risky
• Clonazepam (large doses)
• Diazepam
• Ethosuximide
• Lamotrigine
• Oxcarbazepine
• Topiramate

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Porphyria

• Believed to Be Safe
• Bromides
• Gabapentin

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Patients with mitochondrial cytopathy
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Drugs contraindicated in mitochondrial cytopathy

• VPA
• PB

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Patients on OCPs
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Safe AEDs with OC pills

• Valproate,
• Gabapentin,
• Lamotrigine,
• Levetiracetam,
• Zonisamide

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AED in Pregnancy
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Pregnancy

• Teratogenicity
• The first reports of antiepileptic drug
  (AED)-induced birth defects in humans date from
  the 1960s

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Pregnancy Registry Valproate Carbamazepine Lamotrigine
North American 10.7 2.5 2.7
UK 6.2 2.2 3.2
Finnish 9.7 4
Swedish 10.7 2.7
Australian 13.3 3 1.4
Steven Karceski Epilepsy and pregnancy Are
seizure medications safe? Neurology
200871e32-e33
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• Malformations with valproate doses of 1,100 mg
  per day and greater was 30.2,
• With doses that were lt1,100 mgs was 3.2

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AAN Practice Parameter update

• If possible, avoidance of valproate (VPA) and
  antiepileptic drug (AED) polytherapy during the
  first trimester of pregnancy should be considered
  to decrease the risk of major congenital
  malformations (Level B).

Neurology 200973133141
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AAN Practice Parameter update

• Limiting the dosage of VPA or LTG during the
  first trimester, if possible, should be
  considered to lessen the risk of MCMs (Level B).

Neurology 200973133141
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AAN Practice Parameter update

• Avoidance of the use of VPA, if possible, should
  be considered to reduce the risk of neural tube
  defects and facial clefts (Level B) and may be
  considered to reduce the risk of hypospadias
  (Level C).

Neurology 200973133141
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AAN Practice Parameter update

• Supplementing women with epilepsy with at least
  0.4 mg of folic acid before they become pregnant
  may be considered (Level C).

Neurology 200973142-149
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AAN Practice Parameter update

• Avoidance of PHT, CBZ, and PB, if possible, may
  be considered to reduce the risk of specific
  MCMs
• Cleft palate for PHT use,
• Posterior cleft palate for CBZ use, and
• Cardiac malformations for PB use (Level C).

Neurology 200973133141
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Classification of fetal risks due to
pharmaceuticals.

• Category D
• There is positive evidence of human fetal risk
  based on adverse reaction data from
  investigational or marketing experience or
  studies in humans, but potential benefits may
  warrant use of the drug in pregnant women despite
  potential risks.

United States Food and Drug Administration
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Classification of fetal risks due to
pharmaceuticals.

• Category C
• Animal reproduction studies have shown an adverse
  effect on the fetus and there are no adequate and
  well-controlled studies in humans, but potential
  benefits may warrant use of the drug in pregnant
  women despite potential risks.

United States Food and Drug Administration
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AAN Practice Parameter update

• If possible, avoidance of VPA and AED polytherapy
  throughout pregnancy should be considered to
  prevent reduced cognitive outcomes (Level B).

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AAN Practice Parameter update

• If possible, avoidance of phenytoin and
  phenobarbital during pregnancy may be considered
  to prevent reduced cognitive outcomes (Level C).

Neurology 200973133141
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Other concerns of VPA

• Weight and metabolism
• Menstrual irregularities and polycystic ovaries
• Bone health
• Teratogenic effects

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Choice of AED in pregnant women with JME

• LTG
• Very effective in controlling generalized
  tonic-clonic and absence seizures
• Less effective in controlling myoclonic jerks

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Choice of AED in pregnant women with JME

• Topiramate
• Effective in generalized tonic-clonic and
  myoclonic seizures
• limited efficacy in absence seizures

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Choice of AED in pregnant women with JME

• Zonisamide Levetiracetam
• Effective in primary generalized tonic-clonic,
  absence, and myoclonic seizures

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Pregnancy

• In comparison to valproate, lamotrigine use in
  pregnancy was associated with greater occurrence
  of breakthrough seizures, and dose adjustments
  were more frequently required to maintain seizure
  control
• The increase in seizures may be a reflection of
  the lower serum concentrations known to occur
  during pregnancy.

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AAN Practice Parameter update

• Monitoring of lamotrigine, carbamazepine, and
  phenytoin levels during pregnancy should be
  considered (Level B)
• Monitoring of levetiracetam and oxcarbazepine (as
  monohydroxy derivative) levels may be considered
  (Level C).

Neurology 200973142-149
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Erja Kaaja et al NEUROLOGY 200360575579
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AEDs in Elderly

• Demographic shift

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Elderly are more susceptible due

• to lower hepatic and renal clearance of AEDs
• increase in sensitivity of the central nervous
  system (CNS) to side effects.
• AEDs may affect balance, falls and fractures may
  be related to inappropriate AED use.

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Elderly

• Partial seizures
• Lamotrigine
• Gabapentin
• Carbamazepine

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Elderly

• Generalised seizures
• Valproate
• Topiramate

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Lower seizure threshold
Lower seizure threshold
Lower absorption
Diltiazem Verapamil
Enzyme inducers
Enzyme inhibitor
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Antihyperlipidemic

• CBZ, PB PHT are likely to increase the dose
  requirement of statins
• FBM, LEV, TPM, LTG, OXC, TGB, ZNS, VPA GBP do not
  have any drug interaction

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AED in Hepatic Renal dysfunction
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RENAL AND HEPATICCLEARANCE
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RENAL AND HEPATIC CLEARANCE
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Thank you
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classification of fetal risks due to
pharmaceuticals.

• Category A
• Adequate and well-controlled studies have failed
  to demonstrate a risk to the fetus in the first
  trimester of pregnancy (and there is no evidence
  of risk in later trimesters).

United States Food and Drug Administration
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classification of fetal risks due to
pharmaceuticals.

• Category B
• Animal reproduction studies have failed to
  demonstrate a risk to the fetus and there are no
  adequate and well-controlled studies in pregnant
  women OR Animal studies have shown an adverse
  effect, but adequate and well-controlled studies
  in pregnant women have failed to demonstrate a
  risk to the fetus in any trimester.

United States Food and Drug Administration
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classification of fetal risks due to
pharmaceuticals.

• Category C
• Animal reproduction studies have shown an adverse
  effect on the fetus and there are no adequate and
  well-controlled studies in humans, but potential
  benefits may warrant use of the drug in pregnant
  women despite potential risks.

United States Food and Drug Administration
59
classification of fetal risks due to
pharmaceuticals.

• Category D
• There is positive evidence of human fetal risk
  based on adverse reaction data from
  investigational or marketing experience or
  studies in humans, but potential benefits may
  warrant use of the drug in pregnant women despite
  potential risks.

United States Food and Drug Administration
60
classification of fetal risks due to
pharmaceuticals.

• Category X
• Studies in animals or humans have demonstrated
  fetal abnormalities and/or there is positive
  evidence of human fetal risk based on adverse
  reaction data from investigational or marketing
  experience, and the risks involved in use of the
  drug in pregnant women clearly outweigh potential
  benefits.

United States Food and Drug Administration
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Elderly

• PHT 3 mg/kg
• SSRI Fluoxetine, sertraline and paroxetine

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Antihypertensive

• Diltiazem Verapamil inhibit cytochrome P450,
  thus blood levels of CBZ can rise
• Diltiazem increase PHT levels
• CBZ, PB, PHT can increase the requirement of
  antihypertensive medication
• FBM, LEV, TPM, LTG, OXC, TGB, ZNS, VPA GBP do not
  have any drug interaction

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Anticoagulants and antiplatlets

• CBZ increases the requirement of Warfarin
• FBM is likely to increase the effect of Warfarin

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Analgesiscs

• CBZ will reduce the effect of Fentanyl, Tramadol,
  
• Propoxyphene inhibits metabolism of CBZ
• Cimetidine inhibits VPA
• Omeprazole inhitbits CYP2C19 which inhibit PHT

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Endocrine

• CBZ increase the metabolism of Pioglitazone
• FBM decrease hormone blood levels
• OC increase the clearance of LTG by 50
• PB PHT may cause some enzyme induction and
  alter the metabolism of glypizide Tolbutamide

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Respiratory agents

• PB PHT cause increased clearance of thiophylines

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CNS agents

• CBZ, PB PHT reduce the effectiveness of
  tricyclic antidepresant, mirtazepine, sertaline,
  olanzapine, resperidone, quetiapine, Donepezil,
  Galantamine
• Sertaline increases the bloo
• Fluoxamine, Fluoxytine, tricyclic antidepresant,
  sertaline increase levels of LTG

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Pregnancy

• Women with epilepsy (WWE) should be counseled
  that seizure freedom for at least 9 months prior
  to pregnancy is probably associated with a high
  rate (8492) of remaining seizure-free during
  pregnancy (Level B).

Neurology 200973126132
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Pregnancy

• WWE who smoke should be counseled that they
  possibly have a substantially increased risk of
  premature contractions and premature labor and
  delivery during pregnancy (Level C)

Neurology 200973126132
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• There is insufficient evidence to support or
  refute a benefit of prenatal vitamin K
  supplementation for reducing the risk of
  hemorrhagic complications in the newborns of WWE
  (Level U).

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AAN Practice Parameter update

• There is inadequate evidence to determine if the
  newborns of WWE taking AEDs have a substantially
  increased risk of hemorrhagic complications.

Neurology 200973142-149
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AAN Practice Parameter update

• Primidone and levetiracetam probably transfer
  into breast milk in amounts that may be
  clinically important.
• Valproate, phenobarbital, phenytoin, and
  carbamazepine probably are not transferred into
  breast milk in clinically important amounts.

Neurology 200973142-149
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• It has been known that the overall risk of major
  malformations across AEDs is increased about two-
  to threefold

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• AEDs can produce behavioral teratogenesis, which
  results in cognitive impairment

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VPA

• the risk of malformations with valproate is
  clearly greater than expected, at about 10.7

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AAN Practice Parameter update

• the offspring of women with epilepsy taking AEDs
  are probably at increased risk for being small
  for gestational age (Level B)

Neurology 200973133141
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AAN Practice Parameter update

• The offspring of women with epilepsy taking AEDs
  are probably at increased risk of 1-minute Apgar
  scores of 7 (Level C).

Neurology 200973133141
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Renal failure

• Most drugs require an acidic environment to be
  absorbed.
• Phenytoin and phenobarbital require an acidic
  atmosphere to be absorbed completelys
• Phosphate binders for the treatment of
  hyperphosphatemia (aluminum- or
  calcium-containing) with antibiotics or
  iron-containing supplements may result in the
  formation of insoluble complexes that limit
  absorption and slow gastrointestinal motility.