Pharmacodynamics Flashcards
Define drug receptor. What are its major functions?
A drug receptor is a cellular macromolecule that interacts with a drug and in doing so initiates a series of biochemical events that result in the characteristic action of the drug.
Functions:
- recognition: receptor binds a drug or endogenous ligand
- transduction: transfer of info
Define selectivity in context of drug receptor-mediated processes.
The hundreds of different receptors types and their unique tissue localization impart specificity of drug action; that is, the ability of a drug to exert a distinctive influence on the body.
What are the major mechanisms of receptor-mediated signal transduction?
- G protein-coupled receptor
- Modulate ligand-gated ion channels
- Intrinsic enzyme activity phosphorylates diverse effector proteins
- Regulation of gene transcription
What are the major attributes of drug receptor-mediated processes?
A. Highly compartmentalized; confers drug specificity
B. Self-limiting (most; excepting intracellular hormone receptors); potential basis for drug tolerance
C. Organized into opposing systems; another potential basis for drug tolerance as well as possible drug-drug interactions.
D. Create opportunities for signal amplification
E. Operate through a relatively small number of 2nd messenger systems; another potential basis for drug-drug interactions (essentially an expansion of attribute C).
What are some non-receptor modes of drug action?
- interactions with small molecules or ions
- physiochemical mechanisms
- target rapidly dividing cells
What are the two underlying assumptions of the Occupancy Theory?
- The effect is proportional to receptor occupancy
- Interaction is monovalent
What is the log dose-response curve?
X-axis: log Dose
Y-axis: % maximal effect
Define EC50.
The concentration of the drug producing 50% of the maximal response. An estimate of the drugs KD.
What is affinity?
Affinity, characterized as 1/KD, describes the ability of a drug to form a complex with a receptor.
The greater the affinity of the drug for its receptor the lower the concentration of drug required to occupy the receptor, i.e. its KD and EC50 are small.
Define potency.
A comparative term used to describe the relative positions of several agonist dose-response curves. i.e. if one curve is to the left of another, it is more potent than the other drug.
Define efficacy.
Characterizes the ability of a drug-receptor complex to produce a response.
What is the difference between a full agonist and a partial agonist?
Full: capable of producing maximal response. Alpha =1
Partial: drug whose maximal response is only a fraction of maximum that can be elicited. Alpha is between 0 & 1. In presence of full agonist, it may act as an antagonist.
What are three mechanisms of drug antagonism?
- Competitive: surmountable & reversible. Shifts curve right.
- Non-competive: insurmountable & irreversible. Maximal response decreases. Kd stays same.
- Physiological: involves interactions between pathways mediated by different receptors. e.g. insulin vs. glucocorticoids.
What is an inverse agonist?
A drug that preferentially binds to the inactive form of a receptor (2 state model), shifting equilibrium to the inactive form. This results in an effect the opposite of that produced by an agonist.
What is a spare receptor?
When occupancy of a small percentage of receptors elicits a maximal response, the system behaves as if it has “spare” receptors.
* EC50 & KD values will be different, which is a clear violation of the Occupancy Theory.
