Principles of Pharmacodynamics Flashcards
What is transduction with respect to the drug-receptor concept?
Conf change in receptor leads to altered cellular function via effector molecules (e.g. G-proteins, cAMP, 2ndary msgrs)
What are the 3 drug-receptor concept consequences for pharmacotherapy?
1) Receptor mediates actions of agonists and antagonists
2) Receptors are responsible for selectivity of drug action (think size, shape, charge, etc.)
3) Predicting efficacy and potency through dose-response curve
Explain the theoretical aspects of the hyperbolic shape of the dose-response curve
Assumes binding is reversible and that response is proportional to receptors (R) occupied by drug (D)
Curves generated by increasing dose of drug and measuring response
e/Emax = [D]/EC50 +[D] = [D]/ED50 + [D]
Explain the therapeutic consequences of the hyperbolic shape of the dose-response curve
At low doses: Curve is relatively linear
At high doses: Curve levels off –> there’s a limit to the increase in response (all receptors occupied at high doses —> Emax achieved)
What is potency? Include affinity, Kd, EC50
The concentration (EC50) or dose (ED50) required to produce 50% of that drug’s individual maximal effect — used for comparisons
Depends on affinity (Kd) of receptors binding the drug and efficiency of the drug-receptor complex
What is efficacy? Include power, Emax
Most important determinant of drug’s clinical utility
Limit of the dose-response relationship on y-axis— indicates the relationship between binding to receptor and ability to initiate response
Power often used interchangeably with efficacy
What is an agonist?
Drug that activates its receptor upon binding
Brings about the characteristic tissue response
What is a partial agonist?
Occupy the same receptor as a full agonist, but causes a less than maximum response to full dosage levels
Less effective!
What is a full agonist?
Occupy receptors and causes a full/maximal response
What are 4 types of receptor molecules?
1) Specialized
2) General
3) Proteins
4) Nucleic acids and membrane lipids
What is a specialized receptor molecule?
Membrane proteins or ion channels designed to detect chemical signals and initiate a response via signal transduction pathways
What is a general receptor molecule?
Biological molecules with any function including enzymes, lipids or nucleic acids
What is a protein receptor molecule?
binding site for majority of drugs
Has great specificity (think 2ary, 3ary structure)
Ex: hormone receptor, neurotransmitter receptor
What is a nucleic acid/membrane lipid receptor molecule?
They have lower specificity
What are the advantages of a log dose-response curve vs a regular curve?
1) allows for wide range of doses to be plotted for easy comparison between different drugs
2) Dose-response relationship is a straight line over large range of doses
What is antagonism?
an antagonist is a drug that inhibits the action of an agonist but has no effect in the absence of an agonist
two types: receptor and non-receptor
What is a receptor antagonist? Name three types.
AKA: pharmacological antagonist
Bind to the same receptor as the agonist
1) competitive reversible
2) noncompetitive irreversible
3) noncompetitive allosteric
What is a competitive reversible antagonist?
Reversibly binds to active site of receptor, but does not stabilize the conf change required for activation
Blocks agonist from binding and maintains inactive shape
EC50 increases, Emax unchanged
EX: metoprolol
What is a noncompetitive irreversible antagonist?
covalently/pseudo irreversibly binds to active site — removes functional receptors from system, limiting # available
Noncompetitive = cannot be outcompeted at [high]
Curve shifts downwards, Emax reduced
What is a noncompetitive allosteric antagonist?
Drug binds to different site on receptor than agonist
No competition for receptor binding, but inhibit receptor for binding to agonist
Curse shifts downwards, Emax decreases
What are the two types of non-receptor antagonists?
1) Physiological
2) Chemical
What is a physiological non-receptor antagonist?
activates/blocks a distinct receptor that mediates a physiologic response that is opposite to that of activation of the receptor by agonist
What is a chemical non-receptor antagonist?
Does not involve receptor binding
Occurs via inactivation of agonist itself by modifying/sequestering it —> no longer capable of binding to and activating the receptor
