Anticonvulsants

Question 1

What class is phenobarbital?

Answer 1

barbiturates

Question 2

what is considered a first line agent for the control of seizures in neonates?

Answer 2

phenobarb

Question 3

how effective is phenobarb?

Answer 3

it is frequently ineffective in achieving complete seizure control in neonates

Question 4

what are indications for phenobarb use?

Answer 4

neonatal seizures, generalized tonic clonic seizures, partial seizures and prolonged febrile convulsions; can also be used in NAS and infants with cholestasis (enhances bile secretion)

Question 5

why are newer agents not considered first line?

Answer 5

newer agents (ex: keppra) may develop a role in mgmt of neonatal sz as it becomes more frequently used- more clinical trials are needed

Question 6

what are the advantages of phenobarb?

Answer 6

wide spectrum of phenobarb activity, wide therapeutic range, availability of parenteral and enteral dose forms, low cost and extensive experience of use in peds

Question 7

what are the disadvantages of phenobarb?

Answer 7

resp depressions, sedation, physical dependence, negative cognitive effects, hyperactivity and potential adverse effects on developing neurons

Question 8

what is the effect of age on vol of distribution?

Answer 8

as the infant’s gestation age increases, the vol of distribution decreases ( dec in total body H2O and concurrent increase in total body fat)

Question 9

what is the mechanism of action for phenobarb?

Answer 9

potentiation of inhibitory neurotransmission by prolonging the open state of GABA- mediated sodium channels

Question 10

the suppression of what may also contribute to the therapeutic effects of phenobarb?

Answer 10

the selective suppression of abnormal neurons

Question 11

what is the vol of distribution of phenobarb?

Answer 11

it has a large vol of distribution, distributing into all tissue, 50% bound to plasma protein

Question 12

what is the typical doseage of phenobarb?

Answer 12

loading dose: 20 mg/kg IV; additional doses: 5-10 mg/kg IV Q 30-60 min may be required if sz persist

Question 13

what is the therapeutic level of phenobarb?

Answer 13

30-40 mcg/mL

Question 14

at what rate should phenobarb be administered?

Answer 14

10-15 min

Question 15

what side effects can be seen in serum concentrations of 40-50 mcg/mL of phenobarb?

Answer 15

resp depression &/or coma; bradycardia with levels >50 mcg/mL

Question 16

what side effects can be seen in serum concentrations > 80 mcg/mL of phenobarb?

Answer 16

resp depression &/or death

Question 17

what have current studies demonstrated with regards to phenobarb dosing?

Answer 17

infants may require up to 40mg/kg total loading dose and effective sz control has been r/t phenobarb dose with 70% control in doses of 40 mg/kg

Question 18

what special considerations should be made for infants on ECMO?

Answer 18

require higher doses to achieve effective serum concentrations (r/t large vol of distribution of infant + circuit)

Question 19

what is the half life of phenobarb?

Answer 19

long elimination time, avg 100-200 hours in neonates

Question 20

how is phenobarb metabolized?

Answer 20

primarily in the liver and excreted in urine

Question 21

what class of drug is lorazepam?

Answer 21

benzodiazepine; indicated as an anticonvulsant

Question 22

what is the indication for lorazepam in neonates?

Answer 22

for the acute management of patients with sz refractory to conventional therapy

Question 23

CNS depression is dependent upon what with regards to lorazepam?

Answer 23

dose dependent

Question 24

what is the onset of action of lorazepam?

Answer 24

within 5 min

Question 25

when is peak conc achieved with lorazepam?

Answer 25

within 45 min

Question 26

what is the duration of action of lorazepam?

Answer 26

3-24 hours

Question 27

what is the mean half life of lorazepam?

Answer 27

40 hours

Question 28

what is the typical doseage of lorazepam?

Answer 28

0.05-0.1 mg/kg per dose IV slow push, repeat dosing may be required

Question 29

what should be monitored closely with regards to lorazepam administration?

Answer 29

IV site for signs of phlebitis &/or infiltration; needs close monitoring of renal fx (excreted by the kidneys)

Question 30

what are the adverse effects of lorazepam?

Answer 30

resp depression and some rhythmic myoclonic jerking has been noted in premature infants

Question 31

what class of drug is levetiracetam?

Answer 31

anticonvulsant

Question 32

what are the indications for levetiracetam administration?

Answer 32

2nd line of therapy for sz that are refractory to phenobarb and other anticonvulsants; recently has been used as an alternative to phenobarb in neonates

Question 33

what is the mechanism of action of levetiracetam?

Answer 33

inhibits burst firing without affecting neuronal excitability

Question 34

what is the typical dosing of levetiracetam?

Answer 34

10mg/kg IV Q24h; infuse over 15 min

Question 35

what is the onset of action of levetiracetam?

Answer 35

30 min

Question 36

when is peak conc achieved with levetiracetam?

Answer 36

within 2 hours

Question 37

what is the mean half life of levetiracetam?

Answer 37

6 hours

Question 38

what is the therapeutic serum levels of levetiracetam?

Answer 38

don't routinely monitor drug levels but should be between 10-40 mcg/mL

Question 39

what are the adverse effects of levetiracetam?

Answer 39

overall very minimal; somnolence, fatigue, ataxia, headache and behavioral changes (agitation, hostility, aggression, irritability, depression, nervousness)- difficult to assess in neonates

Question 40

what class of drug is phenytoin?

Answer 40

anticonvulsant

Question 41

how frequently is pheytoin administered?

Answer 41

2nd most commonly administered nonbenzo

Question 42

what are the indications of phenytoin administration?

Answer 42

2nd line therapy for managing neonatal sz, status epilepticus, generalized tonic clonic sz and partial sz with or without secondary generalization

Question 43

what is the mechanism of action of phenytoin?

Answer 43

blockade of voltage-sensitive Na channels, thus inhibiting repetitive neuronal firing

Question 44

what are the additional actions of phenytoin?

Answer 44

alterations of Na, K and Ca conduction, membrane potentials and concentration of AA, norepi, acetylcholine and GABA

Question 45

why are small incremental doses of phenytoin recommended?

Answer 45

as serum phenytoin conc increases, the fraction of drug eliminated per unit of time decreases; small increases in dose can result in disproportionately large increases in the actual serum conc

Question 46

what is the route of metabolism of phenytoin?

Answer 46

hepatic

Question 47

what is the typical doseage of phenytoin?

Answer 47

loading dose: 15-20 mg/kg IV; maintenance dose: 3-5 mg/kg IV Q12h (doses are based on age and wt)

Question 48

why is the rate of infusion of phenytoin important?

Answer 48

slow infusion to prevent cardiac toxicity

Question 49

what is the max rate of phenytoin infusion?

Answer 49

0.5 mg/kg/min

Question 50

what is the only IVF compatiable with phenytoin?

Answer 50

NS; numerous clinically significant pharmacokinetic and pharmacodynamic drug interactions involving phenytoin have been noted

Question 51

what is the therapeutic range of phenytoin?

Answer 51

8-15 mcg/mL

Question 52

why is TDM recommended with phenytoin?

Answer 52

to maximize therapeutic effect and minimize toxicity

Question 53

what are the cardiac toxicity effects of phenytoin?

Answer 53

bradycardias and hypotension; a/w propolineglyco and ethanol consitutents of parenteral formulations