pharmakinetics Flashcards by Carmina Mislang

Dose-concentration relationship
Effects of the biologic system on
drugs

pharmacokinetics

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Deals with the processes of absorption,
distribution and elimination of drugs
Makes possible the calculation of loading
and maintenance doses

pharmacokinetics

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Concentration of a drug at the receptor site
(in contrast to drug concentrations that are
more rapidly measured, eg, blood)

EFFECTIVE DRUG CONCENTRATION

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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

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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)

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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)

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OLUME OF DISTRIBUTION (Vd) EQUATION

Amount of drug in the body
OVER
Plasma drug concentration

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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)

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When a drug is completely retained in

the plasma compartment

 Volume of distribution is equal to the

plasma volume

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2 BASIC PARAMETERS

Rate of elimination compared to plasma
concentration
Depends on the drug and the organs of
elimination in the patient

CLEARANCE (CL)

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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)

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clearance equation

CLEARANCE (CL)
Rate of elimination of drug
over
Plasma drug concentration

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t½
Time it takes for the amount or concentration
of a drug to fall to 50% of an earlier
measurement

HALF LIFE

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Constant regardless of concentration

Drugs eliminated by first-order kinetics

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Particularly useful

Not a constant

Drugs eliminated by zero-order kinetics

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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

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HALF LIFE EQUATION

HALF LIFE
0.693 x Vd
OVER
CL

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Rate of drug administration is equal to
rate of elimination
Dose in=dose out

STEADY STATE CONCENTRATION

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Fraction of the administered dose of the
drug that reaches the systemic circulation
Equal to the amount absorbed over the
amount administered

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

1. IMMEDIATE EFFECT

TIME COURSE OF DRUG EFFECTS Due to distributional delay Delayed expression of the physiologic substance needed for the effect

2. DELAYED EFFECT

TIME COURSE OF DRUG EFFECTS Constant infusion Aminoglycosides causes renal toxicity if given constantly Intermittent dosing only

3. 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

1. ABSORPTION

A. PHARMACOKINETIC VARIABLES Most important parameter in designing dosage regimen Creatinine clearance

2. 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

4. HALF LIFE

PHARMACODYNAMIC VARIABLES Emax No more increase in effect even if the concentration is increasing

1. MAXIMUM EFFECT

A. PHARMACODYNAMIC VARIABLES Increased, exaggerated response to small doses

2. 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