Pharmacokinetics Flashcards
Dose-concentration
Pharmacokinetics
Effects of the biologic system on drugs
Pharmacokinetics
Deals with the processes of absorption, distribution and elimination of drugs
Pharmacokinetics
Makes possible the calculation of loading and maintenance doses
Pharmacokinetics
Concentration of a drug at the receptor site (in contrast to drug concentrations that are more rapidly measured, eg, blood)
Effective Drug Concentration
What the body can do to the drug
Pharmacokinetics
The amount of drug waiting to associate with its receptor
Effective Drug Concentration
How much of the drug can you give initially to a patient.
Loading Dose
How much of the drug should you give to a patient everyday, for the drug to maintain a
certain concentration in the blood of the patient.
Maintenance Dose
Based on trials in healthy volunteers and patients with
average ability to absorb, distribute, and eliminate the drug
“Standard” Dose of a Drug
2 Pharmacokinetic Parameters
1) Volume of Distribution (Vd)
2) Clearance (CL)
Modified by the physiologic and pathologic processes
Pharmacokinetic Parameters
Measure of the ability of the body to eliminate the drug
Clearance
Measure of the apparent space in the body available to contain the drug
Volume of Distribution
Amount of drug in the body to the plasma/serum concentration
Volume of Distribution
Intracellular and extracellular compartments
Volume of Distribution
T/F: Not all of the drug that a patient takes in will take effect, only the effective drug concentration will have an effect on the body.
T
Relates the amount of drug in the body to the concentration of drug (C) in blood or plasma
Volume of Distribution
Drugs with very high volumes of distribution have much _[higher/lower]_ concentrations in extravascular tissue than in the vascular compartment, ie, they are not _[homogeneously/heterogeneously]_ distributed
higher ; homogeneously
T/F: Distribution is faster in muscle, viscera, fat and skin
T
T/F: Initial distribution is in the liver, kidney and brain
T
T/F: Distribution happens in the interstitial and intracellular fluids.
T
Rate of input of the drug (by absorption) into the plasma
Plasma Concentration
Rate of elimination, or loss, from the body
Plasma Concentration
Distribute the drug inside the tissues
Intracellular
Distribute drug outside the cells (e.g. surrounding fluid, blood / systemic circulation)
Extracellular
T/F: Calculated V is an apparent volume that may be appreciated by comparing the volumes of distribution of drugs (e.g., digoxin, chloroquine) with some of the physical volumes of the body.
T
T/F: Volume of Distribution can exceed any physical volume in the body
T
T/F: When a drug is avidly bound in peripheral tissues, it’s concentration in plasma may drop to very high values even if the total amount in the body is large
F; very low values
When a drug is completely retained in the plasma
compartment
High Vd
Volume of distribution is (>, <, =) to the plasma volume
=
2 Major Sites of Drug Elimination
Liver & Kidney
↑ Vd = ___ Plasma Conc.
↓
↑ Vd = Distributed to
Tissues e.g. Urine, Brain
↓ Vd = Stays in the
Blood e.g. Septicemia
Rate of elimination compared to plasma concentration
Clearance (CL)
Depends on the drug and the organs of elimination in the patient
Clearance (CL)
Small water-soluble molecules
Total Body Water (0.6 L/kg)
Ethanol
Total Body Water (0.6 L/kg)
Larger water-soluble molecules
Extracellular Water (0.2 L/kg)
Gentamicin
Extracellular Water (0.2 L/kg)
Large protein molecules
Plasma (0.04 L/kg)
Antibodies
Plasma (0.04 L/kg)
Highly lipid-soluble molecules
Fat (0.2-0.35 L/kg)
Diazepam
Fat (0.2-0.35 L/kg)
Certain ions e.g. lead, fluoride
Bone (0.07 L/kg)
T/F: Total body water in a young lean person might
be 0.5 L/kg; in an obese person, 0.7 L/kg.
F; Young Lean = 0.5, Obese = 0.7
T/F: High Vd can be found in the blood
F; Nowhere to be found in the blood. No matter how much blood taking is performed.
Is the factor that predicts the rate of elimination in relation
to the drug concentration
Clearance
Is similar to clearance concepts of renal physiology
Drug Clearance Principles
T/F: In clearance, drugs are eliminated with first-order kinetics
T
Clearance First-Order Kinetics
Elimination Rate is ____ to Clearance x Plasma Conc.
equal
First-Order = _ Drug Conc., _ Elimination
both ↑
T/F: Clearance is constant and can be calculated via area under the curve (AUC)
T
T/F: Continuous elimination half-life makes the initial concentration smaller & smaller; thus slowing down elimination
T
Clearance of unchanged drug in the urine represents renal clearance
Kidney
Drug elimination occurs via biotransformation, excretion or combination of both
Liver
T/F: For most drugs, clearance is constant over the concentration range encountered in clinical settings
T
2 Types of Elimination in Clearance
1) Capacity-Limited Elimination
2) Flow-Dependent Elimination
T/F: In Capacity-Limited Elimination, clearance will vary depending on the
concentration of the drug achieved
T
A state of “pseudo-zero order” elimination
Capacity-Limited Elimination
Pseudo-Zero Order: At concentrations that are high relative to the Km, the elimination rate is almost __________ of concentration
Independent
T/F: In Capacity-Limited Elimination, if dosing rate exceeds elimination capacity, steady state cannot be achieved
T
T/F: Clearance has no real meaning for drugs with capacity-limited elimination, therefore, AUC should not be used.
T
Drugs are very readily cleared by the organ of elimination
Flow-Dependent Elimination
These drugs are called “high-extraction” drugs
Flow-Dependent Elimination
Type of elimination when blood flow to an organ does not limit elimination, the relation between elimination rate and concentration (C) is expressed mathematically in equation
Capacity-Limited Elimination
Main determinant of drug delivery in flow-dependent elimination
Blood Flow pero pd rin plasma protein binding / blood cell partitioning
Type of elimination when most of the drug in the blood perfusing the organ is eliminated on the first pass of the drug through it.
Flow-Dependent Elimination
Type of elimination wherein it will primarily depend on rate of drug delivery to the organ of elimination
Flow-Dependent Elimination
The time required to change the amount of drug in the
body by one-half during elimination (or during a constant infusion).
Half-Life (t1/2)
Time it takes for the amount of concentration of a drug to
fall to 50% of an earlier measurement
Half-Life (t1/2)
The most useful in designing drug dosage regimens and indicates the time required to attain 50% of steady state or
to decay 50% from steady-state conditions after a change in the rate of drug administration.
Half-Life (t1/2)
T/F: Drugs eliminated by first-order kinetics are constant regardless of concentration
T
T/F: Drugs eliminated by zero-order kinetics are not constant
T
Determines the rate at which blood concentration rises during a constant infusion and falls after administration is stopped
Half-Life (t1/2)
T/F: Half-life depends on both the volume of distribution and the clearance
T
T/F: Drug accumulation happens when repeated drug doses will be accumulated until dosing stops
T
T/F: A change in half-life will not necessarily reflect a change in drug elimination.
T
