Receptors Flashcards
What are some examples of drug targets
Enzymes
Nuclei acids (DNA and RNA)
Carrier molecules or transporters- pump ions across cell membranes
Ion channels- pores across vell membranes that allows ions to enter
Receptors
What are receptors
Highly specialised proteins embedded in cell membranes that possess structurally defined bind in sites which specifically interact with particular complementary sites on the drug molecule
Difference between enzyme and receptor
Enzyme facilitates the reaction
Receptor enables the cell to generate a response
Evidence for receptors
Potency= drugs are highly potent as small quantities are required to produce an effect
Unique actions= drugs can have different actions on different tissues
Specificity
Antagonism= the actions of drugs can be prevented by other drugs
Receptor types
Ionotropic = linked to ion channel, takes ms
Metabotropic= activates G protein and second messenger proteins, takes ms-seconds
Enzyme linked= two receptors, further signalling molecules, takes minutes
Steroid= diffuses against cell membrane, transport to the nucleus for activation of transcription and translation, minutes to Hours
Drug receptor interaction
drug + response = drug response complex= response
Reversible reactions because of weak hydrogen bonds
What does the magnitude of the response depend on
Existence of receptors
Number of receptors occupied by drugs
Intracellular signalling cascade
Potency of a drug
Measure of the ability of a drug to bind to receptor
Measure of potency
Ka= association constant
Kd= dissociation constant = 1/Ka
Efficacy
Measure of the ability of drug- receptor complex to produce a response
Ka/Kb
Agonists
Binds to receptors and produce a response
Antagonists
Binds to receptors but do not activate receptors
Types of agonists
Full agonists= able to evoke a maximal response
Partial agonists= incapable of evoking a maximal response
Inverse agonists
Two state models of receptor function
Agonist = much higher affinity for receptor in active state than R
Partial agonist= will bind to both resting state and active state
Inverse agonist
Agent that binds to a receptor but produces a pharmacological response that is opposite to that of an agonist
Antagonists
Bind to receptors with high affinity but do not activate receptors
How can effect of antagonist be overcome
Increasing the concentration of agonists. This allows more chance for the agonist to occupy the receptor
Schild plot analysis
Calculating dose ratio or competitive shift ratio
pA2
Concentration of antagonist that would produce a shift in dose ratio by 2
What are the two types of antagonist
Reversible competitive antagonist
Non competitive antagonist
Reversible competitive antagonism
The antagonist competes with agonist for the same binding site on the receptor, they occupy the site and Ron a drug receptor complex but no response
Non competitive antagonism
Antagonist binding site is distinct from agonist binding site (allosteric)
Effects are reversible
Allosteric modulation
When the allosteric site is occupied by a drug it can modify the action of the agonist so the agonist - receptor complex might be able to activate the intracellular signalling cascade faster or slower
Receptor desensitisation
Receptors respond less to agonist stimulation over time because
- high concentration of agonist
-repeated exposure of receptors to agonists with insufficient time intervals
