pharmakinetics Flashcards
Dose-concentration relationship
Effects of the biologic system on
drugs
pharmacokinetics
Deals with the processes of absorption,
distribution and elimination of drugs
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
Rate of input of the drug (by absorption)
into the plasma
Rate of distribution to peripheral tissues
(including the target organ)
Rate of elimination, or loss, from the body
PLASMA CONCENTRATION
2 BASIC PARAMETERS
Unique for a particular drug in a particular
patient
Average values in large populations that
can be used to predict concentrations
1. VOLUME OF DISTRIBUTION (Vd)
2. CLEARANCE (CL)
2 BASIC PARAMETERS
Measure of apparent space in the body available to contain the drug Amount of drug in the body to the plasma/serum concentration Intracellular and extracellular compartments
VOLUME OF DISTRIBUTION (Vd)
OLUME OF DISTRIBUTION (Vd) EQUATION
Amount of drug in the body
OVER
Plasma drug concentration
When a drug is avidly bound in peripheral tissues, it’s concentration in plasma may drop to very low values even if the total amount in the body is large
High volume of distribution (Vd)
When a drug is completely retained in
the plasma compartment
Volume of distribution is equal to the
plasma volume
2 BASIC PARAMETERS
Rate of elimination compared to plasma
concentration
Depends on the drug and the organs of
elimination in the patient
CLEARANCE (CL)
Drugs eliminated with first-order kinetics
Clearance is a constant
Elimination rate is equal to clearance times
plasma concentration
Elimination will be rapid at first and slow as the
concentration decreases
CLEARANCE (CL)
clearance equation
CLEARANCE (CL)
Rate of elimination of drug
over
Plasma drug concentration
t½
Time it takes for the amount or concentration
of a drug to fall to 50% of an earlier
measurement
HALF LIFE
Constant regardless of concentration
Drugs eliminated by first-order kinetics
Particularly useful
Not a constant
Drugs eliminated by zero-order kinetics
Derived parameter from the volume of distribution and clearance Determines the rate at which blood concentration rises during a constant infusion and falls after administration is stopped
HALF LIFE
HALF LIFE EQUATION
HALF LIFE
0.693 x Vd
OVER
CL
Rate of drug administration is equal to
rate of elimination
Dose in=dose out
STEADY STATE CONCENTRATION
Fraction of the administered dose of the
drug that reaches the systemic circulation
Equal to the amount absorbed over the
amount administered
BIOAVAILABILITY
BIOAVAILABILITY
Dependent on
Extent of absorption 1 st-pass effect Rate of absorption Site of administration [eg, topical drugs (ointments) which have very slow rate of absorption]
BIOAVAILABILITY
Drugs are more absorbed in the because it has a
small
intestines
larger surface
area
BIOAVAILABILITY
TYPE OF ADMIN THAT GIVES
Unity or 100%
Intravenous administration
BIOAVAILABILITY TYPE OF ADMIN Reduced by incomplete absorption 1 st-pass metabolism Distribution into other tissues before the drug enters the systemic circulation
Administration by other routes
WHAT TO DO TO To offset low bioavailability
Sublingual Rectal-50% probability of bypassing the 1 st-pass effect Inhalation or nasal Transdermal patches
TIME COURSE OF DRUG EFFECTS
Directly related to concentration
Eg, anticoagulants
- IMMEDIATE EFFECT
TIME COURSE OF DRUG EFFECTS
Due to distributional delay
Delayed expression of the physiologic
substance needed for the effect
- DELAYED EFFECT
TIME COURSE OF DRUG EFFECTS
Constant infusion
Aminoglycosides causes renal toxicity
if given constantly
Intermittent dosing only
- CUMULATIVE EFFECTS
Fraction of the drug removed from the perfusing blood during passage to the organ Measure of the elimination of the drug by that organ Drugs with high hepatic extraction ratio have large 1 st-pass effect
EXTRACTION
Desired therapeutic effects are produced
TARGET CONCENTRATION
Plan for drug administration over a period of time Achievement of therapeutic levels of the drug in the body without exceeding the minimum toxic concentration
DOSAGE REGIMENS
Dose needed to maintain a steady state of concentration Maintain plasma concentration within a specified range over long periods of therapy Enough drugs to replace eliminated drugs Clearance is the most important parameter in defining rational drug dosage
MAINTENANCE DOSE
For drugs with long half-lives and longer
time to reach a steady state
Given to promptly raise the concentration
of the drug to the target concentration
LOADING DOSE
LOADING DOSE If the therapeutic concentration must be achieved rapidly and the volume of distribution is large, a --- loading dose maybe needed at the onset of therapy Volume of distribution (Vd) is important
large
PHARMACOKINETIC VARIABLES
Compliance of patient is important
Variation in bioavailability are usually
due to variation in metabolism during
absorption
- ABSORPTION
A. PHARMACOKINETIC VARIABLES
Most important parameter in designing
dosage regimen
Creatinine clearance
- CLEARANCE
- Good indicator of renal function
- Adjust the dosage of the drug
- No reliable indicator for liver function
CREATININE CLEARANCE
PHARMACOKINETIC VARIABLES
Clearance and volume of distribution
- HALF LIFE
PHARMACODYNAMIC VARIABLES
Emax
No more increase in effect even if the
concentration is increasing
- MAXIMUM EFFECT
A. PHARMACODYNAMIC VARIABLES
Increased, exaggerated response to
small doses
- SENSITIVITY
More highly protein bound drug will
displace the less protein bound drug
Inert
PLASMA BINDING PROTEINS
Most appropriate time to measure drug
concentration
Absorption is complete
2 hours after the dose
PLASMA BINDING PROTEINS
Acidic drugs bind to —-
Basic drugs bind to —–
albumin
alpha 1 acid glycoprotein
PLASMA BINDING PROTEINS
More highly protein bound drug will
displace the —— drug
Inert
less protein bound
Average total amount of drug in the body does not change over multiple dosing intervals Rate of drug input equals the rate of elimination Condition in 3 to 4 t ½ must elapse before checking drug blood concentration
STEADY STATE CONCENTRATION
Safe “opening” between the MEC and the MTC of the drug Used to determine the range of plasma levels that is acceptable when designing a dosing regimen
THERAPEUTIC WINDOW
PEAK AND TROUGH CONCENTRATIONS determines the desired trough levels of a drug given intermittently MTC determines the permissible peak plasma concentration
MEC
PEAK AND TROUGH
CONCENTRATIONS
determines the permissible peak
plasma concentration
MTC
