Seizure/SE Drugs

Question 1

BZDs MoA

Answer 1

Bind to GABA-receptor complex and increase GABA-ergic transmission

Question 2

First-line BZD in SE

Answer 2

Lorazepam

Question 3

Second-line BZDs in SE

Answer 3

Diazepam, midazolam

Question 4

ADEs of BZDs

Answer 4

Impaired consciousness, hypotension, respiratory depression

Question 5

Lorazepam dosing

Answer 5

4mg IV (0.1-0.2mg/kg)

Question 6

Diazepam dosing

Answer 6

5-20mg (0.15mg/kg) IV
0.2-0.5mg/kg PR

Question 7

Midazolam dosing

Answer 7

0.15-0.2mg/kg IM

Question 8

Phenytoin/fosphenytoin MoA

Answer 8

Stabilizes neuronal membranes and decreases seizure activity by increasing efflux OR decreasing influx of Na ions across the cell membranes

Question 9

Phenytoin/fosphenytoin ADEs

Answer 9

P-450 interactions
Hirsutism/hypertrichosis
Enlarged gums
Nystagmus
Yellow/browning of the skin
Teratogenicity
Osteomalacia- Vitamin D deficiency
Interference with folate metabolism (anemia)
Neuropathies: vertigo, ataxia, HA
SJS
Neutropenia, thrombocytopenia

Hypotension, bradycardia, QT prolongation → correlated with infusion rate; attributable to propylene glycol

Question 10

Phenytoin/fosphenytoin PK/PD

Answer 10

Peak brain levels: ~6 minutes after infusion is complete
Metabolism: hydroxylation in the liver
Highly protein bound
Eliminated primarily by hepatic metabolism
Follows saturable PK

Question 11

Phenytoin/fosphenytoin dosing

Answer 11

Loading: 20mg/kg IV (max: 50mg/min)

Maintenance: 4-6mg/kg/day in 2-3 divided doses

Question 12

Goal phenytoin levels

Answer 12

10-20mcg/dl of TOTAL phenytoin (trough level)

Actively seizing: target 15-25mcg/dl
Levels >30: seizures
Must correct level for low albumin: <3.5, poor renal function

Question 13

Keppra MoA

Answer 13

Binds to synaptic vesicle protein SV2A → involved in neurotransmitter release

Question 14

Keppra ADEs

Answer 14

Agitation (aggression, anger, emotional lability)
Drowsiness

Question 15

Keppra dosing

Answer 15

20mg/kg IV bolus (max 4.5g)
Maintenance: 1000mg IV BID

Needs adjustment in CKD/AKI

Question 16

Keppra PK/PD

Answer 16

Levels don’t correlate with efficacy

Question 17

VPA MoA

Answer 17

Increases GABA synthesis and release

Reduces excitatory amino acids and attenuate neuronal excitation mediated by NMDA receptors

Blocks voltage-dependent sodium channels → inhibits excitable membranes

Question 18

VPA dosing

Answer 18

Loading: 40mg/kg (max 3g)
Maintenance: 5mg/kg IV q8h, increase PRN based on levels

Question 19

VPA ADEs

Answer 19

Drowsiness, HA
Thrombocytopenia
Pancreatitis (peds patients)
Hyperammonemia

Question 20

VPA PK/PD

Answer 20

Goal levels: 50-100mcg/ml

Question 21

VPA DDI

Answer 21

DDI with phenytoin

Both strongly protein bound
VPA displaces phenytoin off the protein, so there’s more phenytoin available → higher potential for toxicity

Question 22

Lacosamide MoA

Answer 22

Stabilizes hyperexcitable neuronal membranes and inhibits repetitive neuronal firing by enhancing slow inactivation of sodium channels

Question 23

Lacosamide dosing

Answer 23

100-200mg IV BID

Question 24

Lacosamide ADEs

Answer 24

Dizziness, abnormal vision, diplopia, ataxia

Generally well-tolerated

Question 25

Pento/phenobarbital MoA

Answer 25

Suppresses sensory cortex

Question 26

Pentobarbital dosing

Answer 26

5-15mg/kg IV x1
0.5-5mg/kg/hr IV infusion

Question 27

Phenobarbital dosing

Answer 27

Loading: 20mg/kg IV x1
Maintenance: 1-2mg/kg IV BID

Question 28

Pento/phenobarbital ADEs

Answer 28

Respiratory depression (IV)- patients require INTUBATION
Hypotension- may require vasopressors
Lethargy
Nystagmus
Thrombocytopenia
Suppress immune system
Decreased GI motility

Question 29

Ketamine MoA

Answer 29

NMDA receptor antagonist

Question 30

Ketamine dosing

Answer 30

Loading: 1.5-3mg/kg IV x1
Maintenance: 0.1-4mg/kg/hr (max 15mg/kg/hr)