Pharmacodynamics: Dose-response relationship Flashcards
The relationship between the dose (amount) of a drug and the response observed can often be extremely complex, depending on a variety of factors.
These include
absorption
metabolism
elimination of the drug
site of action of the drug in the body
presence of other drugs
disease.
At relatively low levels, Increase in response of a drug is __________ proportional to increase in the dose
Directly
What happens At higher doses?
With an increase in the dose, the amount of change in response gradually decreases until a dose is reached that produces no further increase in the observed response (i.e., a plateau)
The relationship between the concentration of the drug and the observed effect can therefore be graphically represented as a _______________
Hyperbolic curve
Drug- relationship effect is therefore defined as Measurement of the relationship between
_______________ & ________________
the quantity/concentration of a substance and its overall effect on an organism.
_________________ controls the effect of a drug
The concentration of the drug at the site of action
Y axis is known as
X axis is known as
Ordinate
Abscissa
to transform the dose-response relationship into a sigmoidal curve, what is plotted?
Ordinate: response
Abscissa: logarithm of the drug concentration
This transformation makes it easier to compare different dose-response curves—since the scale of the drug concentration axis is expanded at low concentrations where the effect is rapidly changing, while compressing the scale at higher doses where the effect is changing more slowly
From hyperbolic to sigmoid
This representation is more useful because it expands the dose scale in the region where drug response is changing rapidly and compresses the scale at higher doses where large changes have little effect on response. Note that, in reality, it is ligand concentration (and resulting receptor occupation) that affects response - the term ‘dose-response curve’ assumes that the drug dose and ligand concentration are closely linked.
Salient Features of the dose response curve are
Threshold
Slope
E max
How does the body take in toxic insults and still remain healthy?
Below the threshold concentration, there are no adverse effects from exposure to chemical.
Cells in the liver and kidney break down chemicals into non toxic substances to be excreted in urine & feces
Thresholds based on ________________ are more easily determined, while thresholds for ________________ are more difficult to determine.
Acute responses eg death
Chronic responses eg chemicals that cask use cancer
When is slope used
When threshold is difficult to determine, toxicologists look at the slope of the dose-response curve to give them information about the toxicity of a chemical.
Slope is change in response per unit dose
sharp increase in the slope of the curve can suggests that? ___________________
A relatively flat slope suggests that?
As dose increases, there’s a higher risk of toxic responses
Increase in dose gives minimal effect
A steep curve that begins to climb even at a small dose suggests a chemical of
High potency
The potency of a chemical is a measure of
its strength as a poison compared with other chemicals.
Characteristics of LDR curve
Log dose response
i. curve is sigmoid,
2 having between 20 and 80 % as straight lines for statistical analysis eg slope
3 Drugs with a similar mechanism of action have parallel curves.
4 Beyond Emax, further increase in drug concentration cannot produce any increase in response.
- LOG dose is plotted on absicca
- Response is plotted on y axis
Types of drug response relationships
Graded dose-response curve : Intensity of effect
Quantal dose-effect curve : frequency of effect
Characteristics of graded curve
Measured in a single biologic unit
Continuous scale (†dose -› Effect)
Relates dose to intensity of effect
Characteristics of Quantal curve
Used in Population studies
All-or-none pharmacologic effect
Relates dose to frequency of effect
Dose response parameters include
Potency
Efficacy
Relative safety of a drug
POTENCY is a measure of drug activity expressed in terms of
A highly potent drug e.g. ________ evokes a given response at a low concentration. A drug of lower potency e.g. ____________ evokes the same response only at higher concentrations.
the amount of drug required to produce an effect of given intensity.
Fentanyl
Meperidine
Potency is often measured at?
It is also known as
50% concentration/ dose level
EC50 ie efficacy at 50%
Potency is relatively important in clinical use of drugs T/F
False
Potency is relatively unimportant in clinical use of drugs
Efficacy is?
The ability of a drug to produce effect
Emax is
The maximal effect that can be produced by a drug
Efficacy is determined mainly by ___________________ & __________________
the properties of the drug and
its receptor-effector system.
True or False
Efficacy is Important clinical measure.
Partial agonist have greater maximal efficacy than full agonists.
True
False: lower maximal efficacy
_____________ help in estimating the safety of a drug
Dose response curve
Therapeutic Index =
TI = LD50 / ED50
LD50 is?
The median lethal dose of a drug
Types of antagonism are
Pharmacological
Physiological
Chemical
In chemical antagonism,?
Example
caused by combination of agonists with antagonists, with resulting inactivation of the agonists
dimercaprol and mercuric ion
(Dimercaprol is a chelating agent used as an antidote to arsenic, gold, and mercury poisoning, as well as acute lead poisoning)
[Chelating agents are chemical compounds that react with metal ions to form a stable, water-soluble complex. They are also known as chelants, chelators,]
Physiological antagonism is caused by agonist and antagonist acting at two independent sites and inducing independent, but opposite effects. E.g.
histamine and adrenaline.
A physiologic antagonist binds to a different receptor molecule, producing an effect opposite to that produced by the drug it antagonizes. Thus, it differs from a pharmacologic antagonist, which interacts with the same receptor as the drug it inhibits. Familiar examples of physiologic antagonists are the antagonism of the bronchoconstrictor action of histamine by epinephrine’s bronchodilator action and glucagon’s antagonism of the cardiac effects of propranolol.
Pharmacological antagonism is caused by?
•In the case of pharmacological antagonisms, the terms competitive and non-competitive antagonism are used.
action of the agonist and antagonist at the same site.
In Quantal dose effect curve, they are grouped &
Each group is given a different dose
In Quantal experiment, you get 5 parameters.
List and explain these
ED 50 : dose that causes a desired effect on 50% of subjects
TD 50: dose required to cause a toxic effect or undesired effect in 50% of population
LD 50: dose required to kill 50% of the population
TI 50 : LD 50/ED50
High TI is safe eg penicillin
Low TI is unsafe eg digoxin
Margin of safety: ration of LD1/ED99
