Dose- Concentration and Effect Relationship

Dose Concentration Relationship

In order for drugs to have an effect , they must be above a
certain minimum concentration in the body .
When the concentration falls below this value, the effect
disappears. If the dose of the drug is gradually increased, the
effect increases in a dose-dependent manner; When the
concentration reaches a certain limit, the effect reaches its
maximum . An increase in concentration above this limit will
no longer cause a further increase in effect. Below this limit,
the intensity of the drug is proportional to the concentration
at the site of action.
The dosage of the drug should be well adjusted so that the
drug is at the site of action for a sufficient period of time in
the optimal concentration range.

Plasma Concentration-Time Curve:

These are the curves obtained by taking blood samples at
regular intervals after drug administration and measuring
the concentration of the drug in plasma at certain times.
 If the curve is plotted not with the concentration in plasma but with the
concentration in the serum or blood, the curve is called the serum
concentration-time curve and the blood concentration-time curve ,
respectively.

Plasma concentration-time curve:

 Plasma concentration-time curve:
  Administration of the drug in a single dose
 As with long-term treatment, it should be given as repeated doses at fixed
intervals.
 It depends on the route of administration and dose of the drug.
 The most important change in administration as a single dose is seen between
iv injection and other forms of administration. In addition, in iv administration,
iv injection and iv infusion form a plasma concentration-time curve differently.

PLASMA CONCENTRATION-TIME
CURVE IN CASE OF SINGLE DOSE OF
THE DRUG
 If the drug is given as a single dose by intravenous injection, the plasma
concentration is initially highest, then the concentration decreases
exponentially.
 Here Ctp is the plasma drug concentration at the end of the progressive t times
after injection, and bald is the elimination rate constant.

If the drug is injected into the tissue or orally,

the drug concentration in the plasma is
zero at the time of drug administration and
within a few minutes after that, or it is
counted as zero because it is below the
sensitivity limit (the lower limit of
quantification) of the quantitative analysis
method used.
 If the drug is injected into the tissue or orally, the drug concentration in
the plasma is zero at the time of drug administration and within a few minutes
after that, or it is counted as zero because it is below the sensitivity limit (the
lower limit of quantification) of the quantitative analysis method used.
 As absorption progresses, the concentration rises and finally reaches a
maximum (peak) value. After that, the concentration starts to decrease
 gradually. It is "absorption rate> elimination rate" before its peak . At the
climax, the speed of these two events becomes equal for a short time. On the
descending part of the curve is the "elimination rate> absorption rate" .

Elimination begins as soon as the drug

appears in the blood, and therefore , while
absorption occurs on the one hand, and
elimination on the other hand, during the
time corresponding to the outbreak phase of
the curve . During the time that coincides
with the descending phase, absorption ends
at any time and elimination continues for a
relatively long time alone.
 Elimination begins as soon as the drug appears in the blood, and therefore ,
while absorption occurs on the one hand, and elimination on the other
hand, during the time corresponding to the outbreak phase of the
curve . During the time that coincides with the descending phase, absorption
ends at any time and elimination continues for a relatively long time alone.
 The absorption of the drug from the site of administration and its elimination
from the body is usually by simple diffusion, ie exponentially according to
first order kinetics . Therefore, the course of the concentration of the drug in
plasma or its amount in the body with respect to time can be considered as the
algebraic sum of an exponential increase and an exponential decrease.

If the plasma-concentration-time profile is

plotted on an arithmetic scale when drugs are
administered via non- intravenous routes, an
asymmetric parabolous curve is obtained
when the drug is administered via
intravenous routes. If the profile is plotted
semi-logarithmically, the descending part of
this curve (elimination period) is in the form
of a straight line .
 If the plasma-concentration-time profile is plotted on an arithmetic scale when
drugs are administered via non- intravenous routes, an asymmetric
parabolous curve is obtained when the drug is administered via
intravenous routes. If the profile is plotted semi-logarithmically, the
descending part of this curve (elimination period) is in the form of a
straight line .
 The shape of the plasma concentration curve changes according to the ratio
between the absorption rate constant (ka) and the rate constant of elimination
from the plasma (kel) in drug administration through the gastrointestinal tract
or iv route.
 The larger ka is relative to kel (ka is usually 5 times or greater than keI ),
the higher the slope of the extractive phase and the sooner the peak is
reached. If ka is less than bald, the curve becomes flattened and peak
concentration decreases .

There are three important parameters in

terms of pharmacokinetics and
biopharmaceuticals in quantitative
evaluation and comparison of plasma
concentration-time curves:
 There are three important parameters in terms of pharmacokinetics and
biopharmaceuticals in quantitative evaluation and comparison of plasma
concentration-time curves:
 Peak (maximum) concentration value (Cmax),
 Time to peak (time taken from the start of absorption to peak
concentration, tmax)
 The area under the curve is (AUC value).
Peak Concentration and Peak Time
 The peak concentration is defined as the maximum of the potency of the
drug and the time to reach the maximum after the administration of the
drug .
 tmax is a parameter dependent not only on ka but also on kel . As long as
the elimination rate of the drug does not change, the increase in the
absorption rate shortens the peak time. Increasing bald, provided that ka
remains constant, prolongs climax time and decreases peak height .

When measuring tmax, the starting point is

the moment of onset of absorption of the
drug from the site of administration in the
body. Although this point is approximately
equal to the time of administration of the
drug, for oral drugs;
 When measuring tmax, the starting point is the moment of onset of absorption
of the drug from the site of administration in the body. Although this point is
approximately equal to the time of administration of the drug, for oral drugs;
 to the rate of drug release in the pharmaceutical form
 sometimes depending on the absorption of the drug from a certain segment
of the intestine.

There is a considerable time (delay) between the

administration of the drug and the onset of absorption,
ie the appearance of the drug in the plasma. In this case,
the time elapsed between drug administration and
peaking is equal to "delay time + tmax".
 When a drug is administered in increasing doses in a particular route (provided
there is no dose-dependent kinetic change), the peak concentration increases
with little change in the time to peak concentration.
Duration of Drugs:
 The duration of action of the drug begins when the concentration of the
drug at the site of action reaches a certain minimum effective
concentration (MEK) level in the body and continues as long as it remains
above this level.
 It is not possible to take a tissue sample or liquid from the site of action of the
drug and measure the concentration there. However, as a rule of thumb, the
minimum effective concentration value in a plasma corresponding to (often not
equal to) MEK in tissue can be determined experimentally, since the measured
concentration of the drug in plasma reflects the concentration in the tissue.

In the plasma drug concentration time curve

graph, the duration of action can be
calculated from the time remaining between
the points found to draw a horizontal line
from the point in the plasma that matches
the MEK and to take the projection of
the start and end point of the effect of this
line on the time axis.
 In the plasma drug concentration time curve graph, the duration of action can
be calculated from the time remaining between the points found to draw a
horizontal line from the point in the plasma that matches the MEK and to take
the projection of the start and end point of the effect of this line on the time
axis.

PLASMA CONCENTRATION - TIME

CURVE IN THE EVENT OF GIVING
REPEATING DOSES WITH FIXED
INTERVALS
  Drugs are used in most of the medical indications for which they are used, in
certain doses and at certain intervals (intervals), for example every six hours,
three times a day, etc. Like, they are applied for a long time to obtain
continuous effect .
 In this case, the drug cannot reach its effective plasma concentration with
its first dose or the first few doses.
 Repeated administration raises the plasma concentration of the drug to the
desired level within the first day or a few days. Thus, the therapeutic effect
begins after the drug has been applied many times.
 With repeated administration, doses after the first dose are given long before
the plasma level provided by the preceding dose drops to the level at the
beginning of that dose. Therefore, the drug concentration in plasma
increases gradually as the number of repeated doses increases.

Since the rate of drug elimination increases

in proportion to the concentration (kelxC),
such a concentration level is reached in which
the amount of drug eliminated from the body
during the T (or t, tau) interval between two
doses is equal to the dose of the drug.
 Since the rate of drug elimination increases in proportion to the concentration
(kelxC), such a concentration level is reached in which the amount of drug
eliminated from the body during the T (or t, tau) interval between two doses is
equal to the dose of the drug.
 At this concentration, the amount of drug entering the body within the T
interval and the amount of drug exiting the body are roughly equal . This
state is called steady state concentration (Css, steady state concentration). In
such a situation, the plasma level of the drug is said to have reached a
"plateau". At steady state the plasma concentration ranges from a
minimum value to a maximum value.

Important parameters of repeated drug

administration:
Important parameters of repeated drug administration:
 Two practically important parameters in repeated drug administration;
 The magnitude of the concentration at steady state
 This is the time it takes to reach concentration.

1. Steady-state (plateau) Concentration:

 This concentration should be above the MEK value of the drug; but it should
not come too close to the toxic concentration level . The drug concentration
in the plasma at steady state does not follow a steady course, but shows a
regular fluctuation around a steady mean steady state concentration.
 After drug dosing under steady-state conditions , the "rate of absorption>
elimination rate" becomes and the concentration increases from the minimum
steady-state concentration value to the maximum value.
 Then the concentration starts to decrease to a minimum since it is "elimination
rate> absorption rate" . As soon as the minimum is reached, the new dose
has just been given and absorption has begun , at this time the rate of
absorption is equal to the elimination rate . The same changes occur again in
drug concentration in the new dose of plasma.

The amplitude of the fluctuations around the

mean concentration varies with the dose of
the drug as well as the ratio between the dose
interval (T) and the elimination half-life (t1 /
2) of the drug. Fluctuations increase if T is
longer than the elimination half-life.
 The amplitude of the fluctuations around the mean concentration varies with
the dose of the drug as well as the ratio between the dose interval (T) and
the elimination half-life (t1 / 2) of the drug. Fluctuations increase if T is
longer than the elimination half-life.
 Reducing T and the one-time dose correspondingly reduces the amplitude of
the fluctuations.
  Fluctuations are generally considered small unless the T time is longer than the
elimination half-life.
 In clinical practice, the dose interval should be chosen so that the T is neither
uncomfortably short nor the fluctuation in the interval between
doses; otherwise, the concentration may drop below MEK for some time
during each interval and the effect disappears during this time .

If the amplitude of the fluctuations is large ,

the probability that the concentration will
reach MTK (minimum toxic concentration)
increases. If a drug has a small safety ratio or
therapeutic index, the magnitude of
fluctuations is dangerous. In such a case, the
drug may be given by continuous iv infusion
to maintain the effect.
 If the amplitude of the fluctuations is large , the probability that the
concentration will reach MTK (minimum toxic concentration) increases. If a
drug has a small safety ratio or therapeutic index, the magnitude of
fluctuations is dangerous. In such a case, the drug may be given by
continuous iv infusion to maintain the effect.
 To obtain information about the plateau concentration reached during the
treatment and to check whether the sufficient level is reached, determining the
drug concentration in the blood sample is a common procedure in treatment
with some drugs; this is called therapeutic drug monitoring (TDM).
 Since the plateau concentration of the drug fluctuates, the concentration
will vary depending on the time of blood sample collection. In such tests, the
sample is taken at a standard time for standardization of measurements. This
time is just before the administration of repeated doses; The concentration
in the samples taken roughly indicates the Cssmin, ie the "trough
concentration" and this is also called the pre-dose concentration .
The drug's İ.V. The Amount of Drug
Accumulated in the Body and the Plateau
Concentration Achieved in the Case of
Repeated Administration:
 In order to calculate these values, the initial (at t = 0) plasma concentration is
found by extrapolation from the log plasma concentration-time curve drawn by
measuring the drug concentration in blood samples taken at appropriate
intervals after the administration of the first dose of the drug .
 The straight line elimination period of the log plasma concentration-time curve
is extrapolated to the left. The concentration corresponding to the point where
the extrapolation line intersects the vertical axis is equal to CTp1. The starting
concentration for the 1st dose is indicated by the symbol C0p1 and is actually a
virtual concentration.

The fraction of the initial concentration

remaining in plasma at the end of the dose
range, ie the CTp1 / C0p1 ratio, determines
the rate at which the drug accumulates at the
end of each dose interval . This accumulation
parameter called
 The fraction of the initial concentration remaining in plasma at the end of the
dose range, ie the CTp1 / C0p1 ratio, determines the rate at which the drug
accumulates at the end of each dose interval . This accumulation
parameter called
 The concentration immediately after the second dose is equal to the
concentration remaining from the first dose plus the initial concentration that
the second dose would have formed if given alone.

Plateau Concentration Achieved by Oral or

Tissue Administration:
  The change in plasma drug concentration (i.e., Cp) over time (t) after the first
dose (D) fits the following equation:
 Plasma drug concentration (Cp) at the end of a period equal to t (t can be at
most T) from the nth dose when this dose is given orally or by other
intravenous routes at intervals equal to T is calculated from the equation on the
right.

Average Drug Concentration at Steady State

 (Cssort): The mean drug concentration at steady state is an imaginary
parameter derived from the average drug assortment value in the body over the
dose range. This value is calculated from the concept that the rate at which the
drug enters the body and is eliminated from the body is equal throughout the
steady-state dose interval.
 When the drug is administered repeatedly at a fixed dose with equal T
intervals, the size of the Assort varies according to the value of T compared to
t1 / 2, indicative of the accumulation of the drug in the body. According to this
equation, if T is equal to or greater than 1.44.t1 / 2, the drug does not
accumulate in the body; For example, when T = 1.44xt1 / 2, Assort is not
more than the amount of drug (bioavailable) that enters the body after the first
dose.

In order to be able to say that the drug has

accumulated in the body , the Assort
value must be greater than the amount of
drug that is bioavailable (or the dose taken if
F = 1, ie 100%) . With the reduction of T
below this limit, the accumulation (Assort)
increases in inverse proportion.
 In order to be able to say that the drug has accumulated in the body , the
Assort value must be greater than the amount of drug that is bioavailable (or the
dose taken if F = 1, ie 100%) . With the reduction of T below this limit, the
accumulation (Assort) increases in inverse proportion.
  Each drug can accumulate in the body if given in sufficient dosage and
frequently enough; thus, the plateau can be reached by adding the plasma
concentrations generated by the doses.

Time to Reach Steady State Concentration

(accumulation or speed to reach steady
state):
 It is related to the time elapsed after repeated administration until the
therapeutic effect occurs.
 The time or rate involved is not dependent on the dose interval  . The rate
at which the drug concentration reaches steady state is dependent on the
elimination rate constant (keI) and hence the elimination half-life . The rise
of concentration towards steady-state occurs exponentially;
 Plasma concentration reaches 50% of the plateau after an elimination half-life
after repeated administration and 75% after twice the half-life.
 Reaching 100% actually takes a long time as the plasma concentration rises
asymptotically. Therefore, the drug is considered to reach a plateau in plasma
after a period equal to 4 times the elimination half-life from the start of drug
administration; in fact approximately 94% of the plateau level was reached
at this time . At a time point within this time the concentration reaches Cmin
and the drug effect begins.

Loading Dose
 If certain drugs (with a long elimination half-life) are administered
repeatedly, the time taken for their plasma concentrations to reach a plateau
may be too long.
 Sometimes the clinical condition of the patient necessitates an immediate
plateau and immediate effect. In these cases, the drug is given at the loading
dose first, and then the treatment is continued by administering the drug
in a maintenance dose sufficient to meet the one eliminated during the dose
interval .

In patients with renal insufficiency, the

elimination half-life of drugs that are
eliminated from the kidney is significantly
prolonged. In parallel with this, the time
taken to reach the plateau level becomes very
prolonged in patients with renal failure if
even drugs with a short half-life are given
repeatedly. To prevent this, it may be
necessary to administer many drugs in such
patients at the loading dose at the beginning
of the treatment.
 In patients with renal insufficiency, the elimination half-life of drugs that are
eliminated from the kidney is significantly prolonged. In parallel with this, the
time taken to reach the plateau level becomes very prolonged in patients with
renal failure if even drugs with a short half-life are given repeatedly. To prevent
this, it may be necessary to administer many drugs in such patients at the
loading dose at the beginning of the treatment.
 The loading dose of the drug can be calculated by determining the maximum
plasma level obtained when steady state is reached as a result of the
administration of the drug at a fixed dose of D and with a fixed T interval, and
the peak concentration obtained by administering the same dose of the drug in
one single route.

PLASMA CONCENTRATION WHEN THE

DRUG IS DELIVERED BY INTRAVENOUS
INFUSION
 Some drugs are given by continuous iv infusion (such as noradrenaline,
lidocaine, heparin and antibiotics in severe infections) . Here the infusion
rate is usually kept constant and the drug enters the body at a constant rate
( according to zero degree kinetics ). Its elimination, on the other
hand, occurs in the usual way according to first order kinetics .
  If the infusion rate, that is the amount of drug entering the body in a unit time
with the infusion, is Q, the concentration increase in body fluids per unit time
(for example 1 minute) is: Q / Vd. Where Vd is the virtual distribution volume
of the drug.
 If its concentration in plasma reaches a constant value; this is the concentration
value (Css) in the steady state.

At steady state the drug concentration in

plasma is directly proportional to the
infusion rate . If Q is changed, the more times
it increases, the more times the Css value
increases.
 At steady state the drug concentration in plasma is directly proportional to
the infusion rate . If Q is changed, the more times it increases, the more times
the Css value increases.
 The time taken to reach a plateau with intravenous infusion is not dependent
on the infusion rate . This time is dependent on the elimination rate constant
(bald) or the associated elimination half-life (t1 / 2): the same is true with
repeated drug administration .

After starting the infusion, the drug

concentration in the plasma increases
exponentially to reach the plateau and the
half-life of this increase is equal to the
elimination half-life of the drug.
 After starting the infusion, the drug concentration in the plasma increases
exponentially to reach the plateau and the half-life of this increase is equal to
the elimination half-life of the drug.
 When the infusion time is 2 times t1 / 2, the concentration is 75%, 4 times 94%,
and 7 times 99% of the plateau.
  To reach the plateau level, as with other routes of drug administration, an
infusion of roughly 4 times t1 / 2 is required. To shorten this time, the infusion
rate may be temporarily increased at the start of the infusion.
 If the infusion rate is decreased or increased after reaching the plateau
level, the drug concentration in plasma reaches a new plateau level. During the
time it takes to reach the new plateau level, the concentration decreases or
increases exponentially. The "half-life" of this exponential reduction or growth
is also equal to t1 / 2, and the new plateau is reached in a time equal to 4xt1 / 2.

Dose-Effect and Concentration-Effect

Relations
 Quantitative examination of the dose-effect relationship is done according to
two types of dose concepts. One of them is a gradual or stepwise dose , and
the other is a quantum dose that creates a certain effect quantum .
 Gradual dose-effect relationship
 Administration of gradually increasing doses of the drug in a given individual
causes the effect to increase as a function of dose. The effect (E) occurs as a
hyperbolic function of the molar concentration (C), according to a rule that
applies to many agonist drugs acting through certain receptors and for many
systems containing receptors.

EC50 is equal to the dissociation constant

(Kd) of the agonist drug-receptor complex, if
there are no spare drug receptors in the
tissue, that is, if the agonist drug creates its
maximum effect by occupying all of its own
receptors in the tissue .
 EC50 is equal to the dissociation constant (Kd) of the agonist drug-receptor
complex, if there are no spare drug receptors in the tissue, that is, if the agonist
drug creates its maximum effect by occupying all of its own receptors in
the tissue .
 Increasing the dose or concentration in fixed increments (eg twice each time
based on EC50) causes the degree of increase in effect to gradually decrease.
  Dose-response relationship, if the change in a concentration range that is lower
than the EC50 concentration of drug in media including linear happens
relationship.

As a rule, the logarithm of the concentration

or dose is taken as the basis for graphing the
relationship between concentration (or dose)
and effect. In this case, the relationship is
called "log concentration-effect" or "log
dose-effect relationship." The curve thus
obtained is not in the form of a hyperbola,
but in the form of a sigmoid, or letter S. This
approach has two main practical benefits:
 As a rule, the logarithm of the concentration or dose is taken as the basis for
graphing the relationship between concentration (or dose) and effect. In this
case, the relationship is called "log concentration-effect" or "log dose-effect
relationship." The curve thus obtained is not in the form of a hyperbola, but in
the form of a sigmoid, or letter S. This approach has two main practical
benefits:
 Narrows the width of the chart, the horizontal axis, and allows the chart to be
drawn on smaller paper.
 It makes the curve showing the relationship become linear over a larger part of
it.

Kuvantal Dose-Effect Relationship

 In some special cases where the pharmacological effect to be investigated is in
the form of "all or nothing" (for example, relief of headache, relief of vomiting,
prevention of convulsion, determination of the dose that sleeps or kills the
animal), a gradual dose-effect relationship is not in question.
 Due to the biological variability among individuals in terms of drug sensitivity,
the doses sufficient to create an “all or nothing” effect differ between
 individuals. The cuvantal effect can sometimes be a predetermined fixed effect
in accordance with the subject of investigation (for example, reducing diastolic
blood pressure by 10 mm Hg or calcemia by 1 mg / dl).

Kuvantal dose-effect relationship is not

studied on a single individual, but on a large
number of individuals . First, the subjects are
divided into a sufficient number of groups
consisting of an equal number of individuals
and a certain dose of medication is given to
the individuals in each group. The dose is
increased when switching from one group to
another. The additional number of
individuals in each group with respect to the
previous group in which the quanttal effect
occurs is determined; this number is
interpreted as the number of individuals that
require that dose for the effect to occur.
 Kuvantal dose-effect relationship is not studied on a single individual, but
on a large number of individuals . First, the subjects are divided into a
sufficient number of groups consisting of an equal number of individuals and a
certain dose of medication is given to the individuals in each group. The dose
is increased when switching from one group to another. The additional
number of individuals in each group with respect to the previous group in
which the quanttal effect occurs is determined; this number is interpreted as the
number of individuals that require that dose for the effect to occur.
 Ideally a bell-shaped Gaussian curve is obtained if the results are plotted by
showing the doses on the horizontal axis and the number of individuals
requiring each dose on the vertical axis.
The projection of the point on the curve at
50% or its equivalent on the horizontal axis
determines the dose that generates the
cuvantal effect in 50% of individuals; this is
called the median effective dose (ED50) .
 The projection of the point on the curve at 50% or its equivalent on the
horizontal axis determines the dose that generates the cuvantal effect in 50% of
individuals; this is called the median effective dose (ED50) .
 In examining the cuvantal dose-effect relationship, it is not possible to
determine the Emax value of the drug and it is not possible. In this type of
examination, information about the variability of drug sensitivity between
individuals can be obtained and the ED50 value, which is a quantitative
indicator of the drug's efficacy, is determined. If the investigated cutaneous
effect is a toxic effect, the TD50 value (median toxic dose) and the LDS0
(median lethal dose) value can be determined if the examination is performed
on the dose that killed the experimental animal.

Evaluation of Drug Strength and Maximum

Effect (Efficacy) Based on Dose - Effect
Relations
 As a rule, the potency of the drug is determined by another drug with the
same effect . A drug that produces the same type of effect with a smaller
amount (dose or concentration) is stronger than the other drug. Therefore, the
drug with a lower EC50 or ED50 value is stronger than the drug with a higher
value.
 Ideally, comparisons for potency are made between drugs acting on the same
receptor, looking at gradual dose-effect relationships; their log dose-effect
curves are parallel. There is no relationship between the potency of the drug
and the size of its maximum effect (Emax value). A partial agonist drug with a
lower Emax may be stronger than another drug with a higher value but less
affinity for the receptor.
In clinical use, the differences between the
drugs used in the same indication in terms of
potency are generally of no practical value.
 In clinical use, the differences between the drugs used in the same indication in
terms of potency are generally of no practical value.
 Since the dose of the low potency drug is higher in proportion to the low
potency, the same degree of effect is obtained with optimal doses of these
drugs.
 For example, diuretic drugs bumetanide and furosemide increase sodium
excretion by affecting the same segment of nephrons in the kidney and have a
diuretic effect; furosemide is 40 times stronger than bumetanide. The usual
dose of furosemide is 40 mg, and that of bumetanidine is 1 mg. When given at
these doses, the two drugs have the same effect (same amount of diuresis or the
same amount of increase in the volume of urine excreted). The reflection of
the difference in strength on clinical use consists in the fact that the
equiactive doses of the drugs that produce a certain effect differ from each
other in proportion to the difference in power.

The efficacy (efficacy) of a drug compared to

another drug with similar effect is a feature
that is not related to its gravimetric potency.
 The efficacy (efficacy) of a drug compared to another drug with similar effect
is a feature that is not related to its gravimetric potency.
 Accordingly, the efficacy of the drug with low Emax is also low. Although a
drug is less effective than another drug, its potency may be higher. The
reverse is also possible. By looking at the gradual dose-effect relationships of
drugs, information about their potency and effectiveness can be obtained.
 In clinical use, effectiveness has practical value. To increase the therapeutic
effect, a drug with high efficacy is generally preferred to a drug with low
efficacy; Because, in a "treatment-resistant" patient who does not respond
adequately to a drug in treatment, an adequate response can be obtained with a
drug that is similar to that drug and has a higher efficacy.
Drugs A, B, and D, which act on the same
receptor, have equal efficacy, but differ in
potency and are ordered according to
potency as follows: Drug A> B> D> C has less
efficacy than A, B, and D, but this drug is
stronger than D and A is less powerful than.
 Drugs A, B, and D, which act on the same receptor, have equal efficacy, but
differ in potency and are ordered according to potency as follows: Drug A> B>
D> C has less efficacy than A, B, and D, but this drug is stronger than D and A
is less powerful than.

Minimum Effective Concentration (MEK),

Degree of Effect and Selectivity of the Drug
 Concentration of drugs in plasma should rise above the minimum effective
concentration (MEK) regardless of the route of administration . A drug
usually does not have one type of effect, but several types of effects. There is
usually a separate MEK limit for each effect and sometimes the difference
between these MEKs is noticeable.
 The onset and duration of different effects of a drug also differ.
 The higher the peak concentration (Cmax) of the drug is over the MEK
level, the greater the effectiveness or intensity of the drug.

If the drug concentration is too high, the

drug creates toxic effects . These toxic effects;
 If the drug concentration is too high, the drug creates toxic effects . These
toxic effects;
 As it may be due to an exacerbation of the drug at the therapeutic effect site
 It may also be due to the increased concentration of the drug affecting new
places in the body that should be avoided. Thus, drugs also have a minimum
toxic concentration level (MTK).
  The MTK values related to the toxic effect of the drug on different places may
also be different.
 The safety range for different toxic effects is also of different magnitude.

The selectivity of the drug, as a rule, is

determined by looking at the dose that
constitutes the (desired) effect or the
difference between the blood concentration
that constitutes the (desired) effect and the
dose or blood concentration that causes a
toxic effect. If the desired effect and the
undesirable effect are due to the effect of
different receptors or sites by the drug, the
dose-effect relationships of these two types of
effects will be different. The lower the EC50
value or ED50 value related to the desired
effect of the drug than the same values
regarding the undesired effect, the more
selective the drug is. Selectivity partially
reflects the specificity of the drug at its site of
action.
 The selectivity of the drug, as a rule, is determined by looking at the dose that
constitutes the (desired) effect or the difference between the blood
concentration that constitutes the (desired) effect and the dose or blood
concentration that causes a toxic effect. If the desired effect and the undesirable
effect are due to the effect of different receptors or sites by the drug, the dose-
effect relationships of these two types of effects will be different. The lower the
 EC50 value or ED50 value related to the desired effect of the drug than the
same values regarding the undesired effect, the more selective the drug
is. Selectivity partially reflects the specificity of the drug at its site of action.

Selectivity in terms of site of action is

determined by the dose or concentration level
at which the drug affects different sites of
action. If the drug affects the first site of
action in a smaller dose or concentration than
the second site, the drug is said to be selective
or specific to the first site of action. The
degree or extent of selectivity is determined
by the difference between doses or
concentrations .
 Selectivity in terms of site of action is determined by the dose or concentration
level at which the drug affects different sites of action. If the drug affects the
first site of action in a smaller dose or concentration than the second site, the
drug is said to be selective or specific to the first site of action. The degree or
extent of selectivity is determined by the difference between doses or
concentrations .
 Sometimes the toxic effect is only an exacerbation of the desired effect of the
drug. In this case, the desired effect represents the lower part of the dose-effect
curve of the drug and the toxic effect the upper part; If the dose-effect curve is
flat, such a drug has a chance to be highly selective.

Therapeutic index ("therapeutic window"):

The concentration of the drug in plasma
should remain in the area between MEK and
MTK. This area is the range of safety that fits
the therapeutic index of the drug and is also
referred to as the therapeutic window. For
some medications, this area is narrow. Of
particular importance is that they are well
dosed; Such drugs can easily cause poisoning
due to overdose. For example, digoxin , a
heart medication,exhibits significant toxicity
and can be fatal at a dose equal to twice the
therapeutic dose.
 Therapeutic index ("therapeutic window"): The concentration of the drug in
plasma should remain in the area between MEK and MTK. This area is the
range of safety that fits the therapeutic index of the drug and is also referred to
as the therapeutic window. For some medications, this area is narrow. Of
particular importance is that they are well dosed; Such drugs can easily cause
poisoning due to overdose. For example, digoxin , a heart medication,exhibits
significant toxicity and can be fatal at a dose equal to twice the therapeutic
dose.

Relationship between Duration of Effect and

Dose
 Increasing the dose causes the plasma concentration-time curve for each
dose to expand in width and height direction ; It prolongs the action of the
drug . However, the duration of action is not directly related to the dose (D),
but to its logarithm.
 Accordingly, it can be said that the duration of action of the drug changes not
with the logarithm of the dose itself, but with the logarithm of the ratio of this
dose to the "only effective" or "minimum effective" dose (Dmin). When the
plasma concentration is equal to MEK, the total amount of drug (Amin) in the
body can be used and;

Amin = Vd x MEK
If the keI value for a drug is 0.46 / hour and
the drug is administered at a dose of 10 x
Dmin, the duration of action will be 5
hours. If the dose of the drug is increased
three times, the duration increases by
approximately 50% to 7.4 hours. The dose of
this drug needs to be increased 10-fold to
double the duration of action (i.e. to 10
hours), which may result in toxic symptoms.
 If the keI value for a drug is 0.46 / hour and the drug is administered at a dose
of 10 x Dmin, the duration of action will be 5 hours. If the dose of the drug is
increased three times, the duration increases by approximately 50% to 7.4
hours. The dose of this drug needs to be increased 10-fold to double the
duration of action (i.e. to 10 hours), which may result in toxic symptoms.
 Therefore, in order to increase the duration of drug treatment, as a rule, rather
than increasing the dose, repeating the same dose at certain intervals is
preferred, or a modified release form of the drug preparation (MS / MR,
"modified release" tablet or capsule) that slowly releases the drug in the
intestine is used.

If the duration of action of a particular drug

when administered iv is determined
individually for various doses and the times
found are plotted against the logarithm of the
dose, this is seen to be a straight line.
 If the duration of action of a particular drug when administered iv is determined
individually for various doses and the times found are plotted against the
logarithm of the dose, this is seen to be a straight line.
 The horizontal axis of the line gives the value of the breakpoint Dmin. This
applies to drugs whose elimination complies with first order kinetics; It
does not apply to drugs showing dose-dependent kinetics.