Receptors and Dose-Response Flashcards
Drug
A substance that interacts with specific molecular components of an organism to produce a biochemical and physiological response
Pharmacology
The study of drugs
Toxicology
The branch of pharmacology that deals with undesirable effects of chemicals on living systems
Pharmacogenomics
The relation of one’s genetic makeup to the response to a drug - genetically determined differences in drug response
Allosteric modulators
Bind to sites on a receptor but do not prevent the
binding of the agonist
Constituitive activity
Receptor pool that produces similar effect of an agonist
Pharmacodynamics
Actions of the drug on the body
Pharmacokinetics
Actions of the body on the drug
Equilibrium dissociation constant Kd
Represents the concentration for a drug at which half-maximal binding is observed- that is half the receptors are occupied
Potency
The agonist concentration required to elicit a half-maximal effect
Efficacy
The maximal effect of the agonist
Emax
Agonist
Binds to a receptor and stabilizes the receptor in a particular conformation
Antagonist
Binds to the receptor but has no effect in the absence of the agonist
Competitive antagonism
Receptor antagonism which is surmountable, where increasing the agonist concentration restores agonist occupancy
Partial agonist
Produces only a submaximal response due to less than 100% occupancy of receptors
Constituitive activation
An appreciable level of activation existing even when no receptor ligand is present
Inverse agonism
Decreases the level of activation in the presence of constitutive receptor activation
Covalent
Strongest and longest-lasting drug-receptor interaction
Lock-And-Key model
Refers to drugs binding to specific sites on receptors to elicit their effects
Enantiomers
Optical isomers of a drug where often one isomer is more active
Racemic mixture
Commercial preparation of a drug that contains both enantiomers
Therapeutic response
The desired effect of a drug without side effects or toxic effects
Idiosyncratic response
Rare and unpredictable responses, typically not showing a concentration dependence and may be observed at low doses
Receptor
The component of a cell that interacts with a drug and initiates the chain of events leading to the drug’s observed effects
7 TM receptor
Prominent receptor class activating G-proteins to elicit a cellular response
Receptor binding curves
Comparisons among drugs made more readily using a semi-logarithmic scale for the x-axis
High affinity- what happens to Kd?
Lower Kd
Low affinity- what happens to Kd?
Higher Kd
Spare receptors
Maximal effect is obtained at a lower dose than is required for receptor saturation (EC50
Therapeutic index
The relationship between ED50 and TD50
Therapeutic window
Margin of safety of the drug in a population based on TI
When do you only get Kd?
at equilibrium
-the concs of all species are set by the equilibrium
Ro
total conc of occupies and unoccupied Rs
-so total number of receptors
[LR]/ [Ro]
fraction of total receptors occupied by bound L
EC50
potency
E
quantifiable response of a drug
E/Emax
response over max resonse
Example of a system with spare receptors
histamine induced contraction of guinea pig ileum
If ED99 overlaps with LD1 then is the margin of safety low or high?
low
