Flashcards in pharmakinetics Deck (47):
1
Dose-concentration relationship
Effects of the biologic system on
drugs
pharmacokinetics
2
Deals with the processes of absorption,
distribution and elimination of drugs
Makes possible the calculation of loading
and maintenance doses
pharmacokinetics
3
Concentration of a drug at the receptor site
(in contrast to drug concentrations that are
more rapidly measured, eg, blood)
EFFECTIVE DRUG CONCENTRATION
4
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
5
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)
6
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)
7
OLUME OF DISTRIBUTION (Vd) EQUATION
Amount of drug in the body
OVER
Plasma drug concentration
8
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)
9
When a drug is completely retained in
the plasma compartment
Volume of distribution is equal to the
plasma volume
10
2 BASIC PARAMETERS
Rate of elimination compared to plasma
concentration
Depends on the drug and the organs of
elimination in the patient
CLEARANCE (CL)
11
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)
12
clearance equation
CLEARANCE (CL)
Rate of elimination of drug
over
Plasma drug concentration
13
t½
Time it takes for the amount or concentration
of a drug to fall to 50% of an earlier
measurement
HALF LIFE
14
Constant regardless of concentration
Drugs eliminated by first-order kinetics
15
Particularly useful
Not a constant
Drugs eliminated by zero-order kinetics
16
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
17
HALF LIFE EQUATION
HALF LIFE
0.693 x Vd
OVER
CL
18
Rate of drug administration is equal to
rate of elimination
Dose in=dose out
STEADY STATE CONCENTRATION
19
Fraction of the administered dose of the
drug that reaches the systemic circulation
Equal to the amount absorbed over the
amount administered
BIOAVAILABILITY
20
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]
21
BIOAVAILABILITY
Drugs are more absorbed in the because it has a
small
intestines
larger surface
area
22
BIOAVAILABILITY
TYPE OF ADMIN THAT GIVES
Unity or 100%
Intravenous administration
23
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
24
WHAT TO DO TO To offset low bioavailability
Sublingual
Rectal-50% probability of bypassing
the 1 st-pass effect
Inhalation or nasal
Transdermal patches
25
TIME COURSE OF DRUG EFFECTS
Directly related to concentration
Eg, anticoagulants
1. IMMEDIATE EFFECT
26
TIME COURSE OF DRUG EFFECTS
Due to distributional delay
Delayed expression of the physiologic
substance needed for the effect
2. DELAYED EFFECT
27
TIME COURSE OF DRUG EFFECTS
Constant infusion
Aminoglycosides causes renal toxicity
if given constantly
Intermittent dosing only
3. CUMULATIVE EFFECTS
28
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
29
Desired therapeutic effects are produced
TARGET CONCENTRATION
30
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
31
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
32
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
33
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
34
PHARMACOKINETIC VARIABLES
Compliance of patient is important
Variation in bioavailability are usually
due to variation in metabolism during
absorption
1. ABSORPTION
35
A. PHARMACOKINETIC VARIABLES
Most important parameter in designing
dosage regimen
Creatinine clearance
2. CLEARANCE
36
• Good indicator of renal function
• Adjust the dosage of the drug
• No reliable indicator for liver function
CREATININE CLEARANCE
37
PHARMACOKINETIC VARIABLES
Clearance and volume of distribution
4. HALF LIFE
38
PHARMACODYNAMIC VARIABLES
Emax
No more increase in effect even if the
concentration is increasing
1. MAXIMUM EFFECT
39
A. PHARMACODYNAMIC VARIABLES
Increased, exaggerated response to
small doses
2. SENSITIVITY
40
More highly protein bound drug will
displace the less protein bound drug
Inert
PLASMA BINDING PROTEINS
41
Most appropriate time to measure drug
concentration
Absorption is complete
2 hours after the dose
42
PLASMA BINDING PROTEINS
Acidic drugs bind to ----
Basic drugs bind to -----
albumin
alpha 1 acid glycoprotein
43
PLASMA BINDING PROTEINS
More highly protein bound drug will
displace the ------ drug
Inert
less protein bound
44
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
45
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
46
PEAK AND TROUGH
CONCENTRATIONS
determines the desired trough
levels of a drug given intermittently
MTC determines the permissible peak
plasma concentration
MEC
47