Pharmacology Flashcards
volume of distribution
large = distribution into many tissues, usually drug with long half-life
small = highly protein-bound drugs
premature neonates have a higher Vd compared with term infants - decreased protein binding ability due to decreased total protein, albumin, glycoprotein levels
x weight in denominator
zero order kinetics
excrete a constant amount of drug per unit time regardless of serum drug concentrations
linear decrease of serum concentration over time (ex. alcohol)
half-life DEPENDENT on drug dosage (large = cleared more slowly = longer half-life)
fraction of drug that is eliminated is not constant
first order kinetics
excrete a certain percentage of drug per unit time
rate of elimination = serum drug concentration
exponential decrease of serum concentration over time
half life is INDEPENDENT of drug dosage
fraction of drug that is eliminated is CONSTANT
steady state
a state of equilibrium where the amount of drug going in exactly replaces the amount of drug that is excreted
at equilibrium, both the peak and trough levels will be the same for each subsequent dose
half life
time required for the serum drug concentration to decrease by 1/2
approximately 5 half-lives needed to reach steady state (5 t1/2 = 96.875% final steady state concentration
clearance
degree of efficiency a drug is removed from body over time
FIRST ORDER PROCESS = amount of drug removed depends on drug concentration
clearance depends on the infant’s body weight, surface area, volume of distribution, cardiac output, renal/liver function, protein binding of drug
clearance = eliminiation rate constant x volume of distribution
preterm infants have larger Vd = slower clearance compared to term/older children
elimination rate contstant
Kel
FRACTION of the drug eliminated over time
represented by the slope of the log serum concentration decay curve
drugs that interfere with fetal and neonatal oxidation of vitamin K
anticonvulsants: phenytoin, phenobarbital
antituberculosis meds: isoniazid, rifampin
other: warfarin, cephalosporins
drug effects causing increased bilirubin levels
binding albumin and displacoing unconjugated bilirubin from albumin
ceftriaxone, sulfonamides, indomethacin
drug effects causing decreased bilirubin levels
increasing P450 metabolism and increasing the conjugation of bilirubin
phenobarbital, rifampin
serum level
important for:
- drugs with narrow therapeutic range
- drugs with unpredictable dose/response relationship
- drugs with severe toxic effects
- neonates with liver/renal disease
should be drawn during elimination phase (after distribution is completed) and when steady state is reached (5x t1/2)
peak level
dependent on the infusion rate
- longer = lower peak level
dependent on dosage of drug
- high peak = decrease dose of drug
not as useful for antibiotics that display time-dependent killing
trough level
dependent on interval of drug
- high trough = extend interval of drug
most valuable in assessing toxicity risk
for antibiotics with time-dependent killing
- need to keep trough at least 2xx the MIC for specific organism
dosing interval
minimize plasma fluctuations in drug levels
maintain dosing interval >/= half-life
therapeutic window
range of plasma drug concentration with good therapeutic success and minimal toxicity
warfarin and digoxin = narrow therapeutic indexes
penicillin = wide therapeutic index
