Pharmacology – Efficacy & Potency

systemic dose relationship has two components:
Dose – Plasma concentration relationship
-Determined by pharmacokinetics parameters of drug (half life, clearance, volume of distribution)
Plasma Concentration – Response relationship
-Can be studied using in vitro studies

How to Determine a Dose- Response Curve – graded effect is obtained by
administering varying concentration (dose) of drug by intermittent dose method, (washing out preceding dose before adding next). At least 4 to 5 varying doses to cover range between smallest and maximal (largest) response

x and y axis
Doses (x-axis) plotted against response (Y-axis)

Kd (Kdose)
concentration of drug required to occupy half of receptors

threshold dose
Lowest amount or exposure level at which a specified and measurable effect manifests.

maximum dose (Bmax)
The highest dose of a drug or treatment that does not cause unacceptable side effects and no matter how much you add you will have a plateau

What is ED50 (aka EC50)
effective dose/effective concentration: the concentration of drug that produces 50% of the maximal response

Affinity means
whether it gives a response or not
Ability of drug to combine with receptors and produce pharmacologic response (R)

potency
acting on same receptor – amount of drug needed to produce response
a little dose of one produces the effect that more of another drug would = more potent

Efficacy
Maximal response produced by drug observed at saturation – adding more not beneficial

Full agonist
Drug with high efficacy to elicit a maximal tissue response. The higher the affinity of drug
to the Receptor the lower the concentration

Partial agonist
Drug with intermediate level of efficacy, such that even when 100% of the receptors are occupied, the tissue response is submaximal
It activates Receptors to produce sub maximal effect – eg: Nalorphine

Inverse Agonist:
it binds to the same Receptor of an agonist but induces an effect opposite to the agonist
GABA-R : Benzodiazepenes are sedatives while beta-carbolines are anxiogenic to convulsives

Agonist potency depends:
Affinity & Efficacy

Antagonist efficacy and affinity
zero
it has +ve affinity and -ve efficacy

Agonist example
ACh , Histamine

Antagonist example
Have affinity but no efficacy Atropine-Ach

Efficacy of inverse, agonist, competitive antagonist and partial agonist
Inverse: -ve efficacy, agonist: +ve, competitive antagonist: zero, partial: intermediate

Other words for antagonist
blocker inhibitor

How do you overcome a competitive antagonist
add agonist to compete

How do you overcome a non-competitive antagonist?
Cannot compete – wait for receptor turnover

Therapeutic Index
ratio of therapeutic dose to toxic dose (death) – baed on response curves

The formula for therapeutic dose is
Median lethal dose / Median effective dose LD50/ED50

Example of drug toxic at high dose and safe at high dose
toxic – warfarin
safe – penicillin

Receptor Desensitization
loss of drug effect due to change in R- responsiveness

Mechanisms of receptor desensitization
Several mechanisms:
Tachyphylaxis (diminished effect), R are present but unresponsiveness
Down regulated -R undergoes endocytosis so less number of R are available
Rest period in certain drugs as LA

EC50 the drug concentration giving 50% maximal effect (not binding affinity – the magnitude of a drug effect is not proportional to the proportion of receptors occupied by that drug) a drug with a lower EC50 is more potent (half …

What does it mean that DR interactions are concentration dependent? It means that as the concentration of the drug increases the % of receptors bound increases What does it mean the DR interactions are saturable? At a certain concentration 100% …

1. A drug, given as a 100-mg single dose, results in a peak plasma concentration of 20 μg/mL. The apparent volume of distribution is (assume a rapid distribution and negligible elimination prior to measuring the peak plasma level): A. 0.5 …

What is pharmacokinetics? study of drug movement through the body What are the 4 elements of Pharmacokinetics? absorption, distribution, metabolism, excretion WE WILL WRITE A CUSTOM ESSAY SAMPLE ON ANY TOPIC SPECIFICALLY FOR YOU FOR ONLY $13.90/PAGE Write my sample …

Absorption refers to the movement of drug into the bloodstream, with the rate dependent on the physical characteristics of the drug and its formation. Refers to the passage of drug molecules from the site of administration into the circulation. Active …

Paracelsus who is the father of pharmacology and said “all things are poison and nothing is without poison, only the dose permits something not to be poisonous” DOSE MAKES THE POISON (1493-1541) Pharmacology study of interactions of substances with living …

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