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Pharmacokinetics is defined as the study of the time course of
- drug absorption
- distribution
- metabolism
- excretion
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CLinical pharmacokinetics
application of pharmacokinetics to the safe and effective management of drugs in an individual
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Principle application of clinical pharmacokinetics
- increase effectiveness
- decrease toxicity
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Pharmacodynamics
relationship between drug concentration at the site of action and pharmacologic response
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fluid most often sampled for drug concentration
blood
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describes the predictable relationship between plasma drug concentration and concentration at the receptor site
kinetic homogeneity
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If the plasma drug concentration is decreasing, the concentration in the tissues will _____.
decrease
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Plasma concentration that is effective and safe in treating specific diseases
therapeutic range
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boundaries dividine subtherapeutic, therapeutic and toxic drug concentrations
no absolute boundaries
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Variability in patient's response is influenced by both
pharmacodynamic and pharmacokinetic factors
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pharmacokinetics of a drug determine
blood concentration achieved
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Pharmacokinetic factors causing variability in the plasma drug concentration
- differences in individual metabolism and elimination
- variations in absorption
- disease states or physiologic states
- drug interactions
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Determination of plasma drug concentrations to optimize a patient's drug therapy is known as
therapeutic drug monitoring
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Two components of therapeutic drug monitoring
- assay for [drug] in plasma
- interpretation of resulting concentration to develope a safe drug regimen
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Therapeutic monitoring is valuable when
- good correlation exists between pharmacologic response and plasma concentration
- wide variation in drug levels in patients
- drug has a narrow therapeutic index
- drug's effects cannot be measured by other means (BP)
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Value of therapeutic drug monitoring is limited in situations where
- no well defined therapeutic [plasma] range
- formation of active metabolites
- toxic effects at low and high concentrations
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compartmental models are called "deterministic" because
the observed drug concentrations determine the type of compartment model required
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describes change in the amount of drug in the body
elimination rate
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Bolus
drug dose is given over a very short time
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Concentration of a drug =
amount of drug/volume in which it is distributed
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Volume of distribution
extent of drug distribution into body fluids and tissues
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usually indicates that the drug distributes extensively into body tissues and fluids
large volume of distribution
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indicates limited drug distribution, possibly into the plasma only
small volume of distribution
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When V is many times the volume of the body
drug concentrations in some tissues may be higher than in the plasma
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The smallest volume that a drug may distribute in is
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A straight line is obtained from the natural log of plasma drug concentration versus time plot only for drugs that follow
first order elimination
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First order elimination occurs when
amount of drug eliminated depends on the amount of drug in the body at that time
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A large volume of distribution indicates that
a larger dose should be administered to achieve a target concentration
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volume of extracellular fluid in the body
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Extracellular fluid is made up of
plasma and interstitial fluid
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fluid portion in combination with formed elements
blood
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fluid portion of blood
plasma
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fluid portion of blood when soluble protein fibrinogen is removed
serum
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To examine the one compartment model, two assumptions are made
- distribution and equilibration is instantaneous
- elimination is first order
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Amount of drug eliminated for each timer interval is constant, regardless of the amount in the body
zero order elimination
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the fraction of a drug in the body eliminated over a given time remains constant in
first order elimination
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natural log of concentration vs. time plot is linear
first order elimination
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plasma concnetration vs time plot is linear
zero order elimination
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ln of plasma concentration vs time plot is non-linear
zero order elimination
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A steep slope indicates a ____ rate of elimination than a flat slope
faster
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slope =
- elimination constant
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fraction of drug removed over a unit of time
elimination rate constant
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equation for ln C
ln C = (-K x t) + ln C0
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time necessary for the concentration of drug in the plasma to decrease by one half
half life
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half life expresses the same idea as
elimination rate constant
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first order reaction T1/2 =
0.693/K
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Dependent variable
concentration
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independent variable
time
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T1/2 for zero order half life
= 0.5(At)/K0
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Half life is not a constant and will decrease as the process continues
zero order half life
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Mammillary compartment model
grouped around a central compartment
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Volume of distribution = 5 L
entire blood
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Half life is constant and will not change as the process continues
first order half life
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Idea behind pharmacokinetics
know the concentrations at times labs were drawn
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slope of a first order plot =
-k/2.303
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Clearance has the units of
- flow
- volume per time (ml/min, L,hr)
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the rate at which a volume of blood is being cleared from drug molecules
clearance
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