Phenytoin - Day 5 Students PDF

PHARMACOKINETICS PHENYTOIN JOHN M. TOVAR, PHARMD Associate Professor PCOM School of Pharmacy  What I Will Learn Objectives Discuss phenytoin’s MOA, therapeutic uses, 1 main adverse events and key pharmacokinetic parameters. 2 Determine an a...

PHARMACOKINETICS PHENYTOIN JOHN M. TOVAR, PHARMD Associate Professor PCOM School of Pharmacy  What I Will Learn Objectives Discuss phenytoin’s MOA, therapeutic uses, 1 main adverse events and key pharmacokinetic parameters. 2 Determine an appropriate phenytoin loading dose and maintenance regimen. Determine when to draw phenytoin levels and 3 how to use them to calculate patient specific pharmacokinetic parameters.  rector dimers Remember salt we both is are Phenytoin M umon can waitin Phenytoin 1460W 1 MOA? voltagegated Na channel blocker IV and PO class 1b 2 What do we use it for? seizures arrhythmia digitalis toxicity Fosphenytoin Alannah ortoxic 3 Loading doses? IV and IM ifeng.ly ffff usually used in run epilepticus LD Main adverse events? 4 4 nkr an gingival hyperplasia Impedfort O  Remember Fosphenytoin 1 Water soluble (doesn’t require propylene glycol to remain in solution) can be given IM. Can be infused faster (100-150 mg of 2 PE's/min) Converted into phenytoin by phosphatases in 3 the liver and RBCs. Lower risk of cardiac arrhythmia and 4 hypotension than phenytoin. 1.5 mg of fosphenytoin = 1 mg phenytoin and 5 is referred as 1 mg phenytoin equivalents (PE)  Pharmacokinetics Phenytoin Absorption F is 100% S for phenytoin = 0.92 Therapeutic Range S for fosphenytoin = 0.66 10-20 mg/L S for PE = 0.92 Distribution 90% protein bound (only free is active) formula 0.65 L/kg (always use TBW) be on will sheet Beringer P. (2018). Wunter’s Basis Clinical Pharmacokinetics. Lippincott Check levels 8-12 hours after last oral dose or 1 Williams & Wilkins hour after the end of the infusion (if IV)  Pharmacokinetics Digoxin phenytoin MG Metabolism Liver – CYP 2C9/2C19 hepatic enzymes that are Michaelis-Menten saturated with the drug at concentrations within the Kinetics therapeutic range. Elimination Liver metabolism to inactive metabolites Renal 10 mg/kg/day, use 7 mg/kg/day Km = Michaelis-Menten constant, represents the concentration of phenytoin at which the rate of this enzyme-saturable hepatic metabolism is one-half of maximum Beringer P. (2018). Wunter’s Basis Clinical Pharmacokinetics. Lippincott Km = 1 to 15 mg/L, use 4 mg/L Williams & Wilkins  Pharmacokinetics Phenytoin Population-Based T90% = Km x Vd [(2.3 x Vmax)-(0.9 x MD)] (Vmax – MD)2 Vmax = maximum amount of drug that can be metabolized per unit time in mg/day Km = Michaelis-Menten constant, represents the concentration of phenytoin at which the rate of this enzyme-saturable hepatic metabolism is one-half of maximum Beringer P. (2018). Wunter’s Basis Clinical Pharmacokinetics. Lippincott Williams & Wilkins  O TRUE OR FALSE If the daily dose of phenytoin exceeds Vmax, then steady state is never achieved. DOSING CALCULATIONS LD 20 85Ky Practice MD 15 85kg Problem 1 RW, a 50 year-old man is admitted to the hospital with status epilepticus that was successfully treated with IV lorazepam. Pertinent clinical data include weight, 85 kg; height, 6’0”; SCr, 1.6 mg/dL; and serum albumin, 4.6 g/dL. His physician has written an order for the pharmacy to calculate and order an IV phenytoin loading dose, recommend an initial oral maintenance dose, and order timing of plasma concentrations