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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



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

PEAK AND TROUGH
CONCENTRATIONS
determines the permissible peak
plasma concentration

MTC

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