Applied PK Exam 1: Nguyen

ASMs

• 1st Gen ASMs: _____, _____, and _____

• 2nd Gen ASMs: _____ and _____

Carbamazepine, Phenytoin, Valproic Acid, Lamotrigine, Levetiracetam

Absorption

• ASMs and Absorption

  • Only the following ASMs come in _____ formulations

    • _____ (_____®)

    • _____ (_____®)

    • _____ (_____®)

IV, Phenytoin, Dilantin, Fosphenytoin, Cerebryx, Levetiracetam, Keppra

Absorption

• Loading and Maintenance Doses

  • Loading dose definition: An initial higher dose of a drug that may be given at the beginning of a course of treatment before dropping down to a lower maintenance dose

  • IV Loading Doses vs PO Maintenance Doses:

    • Phenytoin _____ mg/kg (max _____ mg) → _____ mg PO qhs

    • Fosphenytoin _____ PE/kg (max _____) → _____

    • Levetiracetam _____ mg/kg (max _____ mg) → _____ mg BID

20, 1500, 300, 20, 1500, None, 60, 4500, 1000-1500

Absorption

• Phenytoin and Fosphenytoin

  • _____ will precipitate out of the solution

  • _____ is dosed as phenytoin equivalents (PE) to make dosing  _____ with phenytoin

  • Serious but rare SEs can occur with _____ administration

  • _____

  • Severe _____ and _____ cardiac _____

  • To prevent these serious ADEs _____ administration is required

    • Phenytoin → rate should not exceed _____ mg/min

    • Fosphenytoin → rate should not exceed _____ mg/min (_____ than Phenytoin)

  • Some hospitals also require close _____ monitoring (due to severe hypotension) and _____ monitoring

Phenytoin IV, Fosphenytoin, interchangable, fast IV, Purple Glove Syndrome, hypotension, life-threatening, arrhythmias, slow IV, 50, 150, 3x more, BP, ECG

Absorption

• Other issues with absorption

  • Phenytoin administered with tube feeds _____ the _____ of phenytoin in the gut

  • Must stop tube feeds ~_____ and ~_____

  • Therapeutic Drug Monitoring (TDM)

  • Phenytoin/Fosphenytoin

    • Total: _____ mg/L

    • Free: _____ mg/L

reduces, absorption, 2 hours prior, 2 hours after, 10-20, 1-2

• Assessment: _____ Phenytoin = Phenytoin is being given with _____

• Recommendation: Stop _____ to phenytoin administration and _____ phenytoin administration

undetectable, tube feeds, tube feeds 2 hours prior, 2 hours after

ENTER AFTER EACH FILLED BULLET POINT

• Phenytoin

  • Phenytoin _____ mg/kg (max _____ mg) → PHT _____ mg PO qhs

  • _____ mg/kg x _____ kg = _____ mg but max is _____ mg

  • Loading Dose: _____ mg

  • No more than _____ mg/min for slow IV administration → _____

• Fosphophenytoin

  • Fosphenytoin _____ PE/kg (max _____ mg) x _____ kg = _____ mg but max is _____ mg

  • Loading Dose: _____ mg 

  • No more than _____ mg/min for slow IV administration → _____

20, 1500, 300, 20, 80, 1600, 1500, 1500, 50, 30 mins

20, 1500, 80, 1600, 1500, 1500, 150, 10 mins

• Close _____ monitoring

• 3 SEs of IV Phenytoin

  • _____

  • _____

  • _____

• Why? Contains propylene glycol, which can cause _____ (especially if infused too quickly).

• Fosphenytoin: Less likely to cause this because it is water-soluble and does NOT contain propylene glycol.

• Phenytoin = _____ (propylene glycol)

• Fosphenytoin = _____

BP and ECG, Purple Glove Syndrome, Severe hypotension, life-threatening cardiac arrhythmias, cardiac toxicity, heart problems, safer IV option

Distribution

• Many ASMs are highly protein bound

• In _____ individuals, phenytoin is _____% protein bound

• _____ phenytoin is pharmacologically _____

• In patients with _____ status there is less <_____% protein binding

• Total phenytoin in blood = _____ mg/L

normal, 90, only free, active, low protein, 90, 10-20

KNOW IMAGE

• Corrected PHT (mcg/mL) = (Observed Total PHT (mg/L)) / [(0.1xalbumin g/dL) + 0.1]

• _____ / [(0.1 x _____) + 0.1] = _____ (Total phenytoin in blood = _____ mg/L) → _____

9, 2.5, 25.7, 10-20, high

Metabolism

• ASM Inducers

  • _____ CYP or UGT enzyme activity

    • _____ clearance of other drugs

    • _____ levels of other drugs

increase, increased, decreased

Metabolism

• Some Examples

  • ASM + ASM

    • PHT + LTG: PHT _____ clearance of LTG via UGT induction, and _____ LTG level to _____-therapeutic

increases, decreases, sub

Metabolism

• ASM Inhibitors

  • Inhibitors decrease CYP or UGT enzyme activity

    • _____ clearance of other drugs 

    • _____ levels of other drugs

decreased, increased

Metabolism

• Some Examples

  • ASM + ASM:

    • VPA + LTG: VPA _____ clearance of LTG via UGT inhibition, _____ LTG and causes _____-therapeutic levels and toxicity (rashes/SJS)

decreases, increases, supra

Elimination

• A handful of ASMs are renally (or partially renally) eliminated and require _____ in patients with _____ → _____

• Phenytoin _____ elimination

dose adjustment, renal disease, Levetiracetam, nonlinear

Elimination

• What does this mean in real life?

  • _____ of phenytoin _____ at _____ doses

  • At that point, a _____ change in dose can lead to a _____ in phenytoin _____

  • A typical phenytoin dose is _____ mg daily

elimination rate, decreases, higher, small, large increase, levels, 300

• Typical maintenance dose: Lev _____ mg PO BID OR Lev _____ mg PO BID

• Levetiracetam is _____ and requires _____ in patients with _____.

• The lower dose of levetiracetam _____ after HD session is an appropriate renally adjusted dose for FM.

1000, 1500, renally eliminated, renal dose adjustment, compromised renal function, 500 mg PO QD

• Current dose: Phenytoin 100 mg TID = _____ mg/day

• Corrected phenytoin level: _____ mg/L

• Therapeutic range: _____ mg/L

• Phenytoin follows _____ (zero-order) kinetics

  • Small dose increase → _____ in drug levels

  • Risk of _____ with _____ dose adjustments

• Dose Recommendation:

  • Level is _____ therapeutic → make a _____

  • Increase by _____ mg/day

  • New dose: _____ mg/day

• Avoid large dose increases with phenytoin because metabolism can become saturated → _____ → _____

• Recheck phenytoin level after reaching steady state

• Remember: _____ level + phenytoin = _____ only (_____ mg/day) due to _____ kinetics.

• Therefore, since FM is already getting 300 mg total daily dose, the recommendation is to _____ total daily dose by

  • _____ increments instead of _____ increments until steady state levels between _____ mg/L are reached

300, 9.5, 10-20, nonlinear, large increase, toxicity, aggressive, slightly below, small dose increase, 25-50, 325-350, rapid increase in concentration, toxicity, low, small dose increase, 25-50, nonlinear, increase, 30 mg, 100 mg, 10-20