Quantitative Aspects of Drugs Flashcards
Define Receptor
A protein whose function is to recognise and respond to an endogenous chemical signal
Other macromolecules with which drugs interact to produce their effect are known as a drug target
How does the pharmacological definition of receptor from a general definition?
Differ from conventional pharmacological receptors in that they respond to protein attached to cell surfaces or extracellular structures, rather than to soluble mediators
How are receptors classified?
Classification and Refinement in drug design is based upon where the action of a drug can be associated with a particular receptor
Ex. H1 receptor vs H2 receptor
What other ways can receptors be classified?
- Direct measurement of ligand binding to receptor
- Molecular sequencing of amino acid structure
- Analysis of biochemical pathways
Define Affinity
Affinity can be defined as the extent or fraction to which a drug binds to receptors at any given drug concentration or the firmness with which the drug binds to the receptor
How is affinity related to potency?
Affinity is one of the factors that determine potency. Affinity is inversely proportional to the potency of a drug (1/ Kd ) , where Kd is the dissociation constant
Define potency
Potency is a measure of necessary amount of the drug to produce an effect of a given magnitude. In general, potency is denoted as the median effective concentration/dose as EC50/ED50/Kd
Define efficacy
Efficacy (intrinsic activity) is the ability of a drug to illicit a pharmacological response (physiological) when interaction occurs with a receptor (relationship between response and occupancy of receptor).
Efficacy depends on the efficiency of the receptor activation to cellular responses and the formation of number of drug-receptor complexes
Why is specificity important?
For a drug to be useful as either a therapeutic or a scientific tool, it must act selectively on particular cells and tissues
Tricyclic antidepressant drugs act by blocking monoamine transporters but are notorious for producing side effects related to their ability to block other receptors
What does Schild Equation show about antagonism?
Used to investigate antagonist action
- Determines whether antagonism is competitive in nature
- Determine equilibrium constant for binding of the antagonist
What is dose ratio?
Factor by which the concentration of agonist needs to be increased by to obtain the same response in the presence of the antagonist as was obtained in its absence
r = 1 + ([B] / KB)
What should you observe if the antagonist is competitive in nature?
- Parallel Shifts to the right in the concentration-response curve
- A log-log plot of r=1 against the antagonist concentration gives a straight line with a slope equal to unity
- No decrease in the maximum response that can be achieved
The latter point is difficult to be certain about because receptor desensitization and tachyphalaxis of tissue responses often make it impossible to obtain the same maximum response
Define pAX
defined as the negative logarithm to base 10 of the molar concentration of an antagonistic drug which will reduce the effect of a multiple-dose (x) of an active drug to that of a single dose
What is a partial agonist?
A ligand that produces a submaximal response
How does efficacy relate to partial agonists?
Differences in levels of responses at a given level of occupancy can be expressed quantitatively in terms of efficacy
A partial agonist has lower efficacy, such that 100% occupancy elicits only a submaximal response
