Drug Receptors and Pharmacodynamics (M1) Flashcards
As the dose of a drug increases, what does the response increment do?
diminishes
What is the concentration-effect curve equation?
E = (Emax*C)/(C+EC50) where EC50 is concentration of drug that produces 50% of maximal effect
What is the ability of a drug to initiate a cellular effect?
efficacy (or intrinsic activity)
What are drugs that have both receptor affinity and efficacy?
agonist
What are drugs that bind to receptors (affinity) but do not activate them?
antagonist
What is the affect of an irreversible antagonist (noncompetitive)? 1. What kind of bonds do they generally form? 2
- reduces maximal effect the agonist can achieve and may not affect EC50
- covalent bonds
What bind to separate sites on the receptor protein and alter receptor function without blocking the receptor?
allosteric modulators
What are the enzyme effector systems with transduction though G-proteins?
- adenylyl (adenylate) cyclase
- guanylyl cyclase
- phospholipase C
What are the second messengers for transduction though G-proteins?
- cAMP
- cGMP
- IP3
- DAG
What are the protein kinases for transduction though G-proteins?
- cAMP-
- cGMP-
- calmodulin-dependent protein kinase C
What is the result of antagonists upregulating the number of receptors?
supersensitivity
What are examples of ion-channel- coupled ligand receptors?
- serotonin
- GABA
- glutamate
- acetylcholine
What mediate the signaling in enzyme-coupled receptors?
- EGF
- PDGF
- ANP
- TGF-Beta
- other tropic hormones
What make up the polypeptides in enzyme-coupled receptors?
- extracellular hormone-binding domain
- cytoplasmic enzyme domain
- hydrophobic connecting segment
What happens, upon the binding of the ligand to the extracellular domain in enzyme-coupled receptors?
receptor molecules bind together (dimerization) and become active and phosphorylate each other
What are tyrosine kinase inhibitors useful for?
neoplastic disorders
For graded dose-response relationships, what is on the x-axis? 1. y-axis? 2
- log dose of drug
2. percentage of the maximal response
What does the potency depend on?
- affinity
2. efficiency drug-receptor interaction coupled response
What is the effect of competitive antagonists on the dose-response curve?
- shift curve to right
2. does not reduce maximal response
What is the effect of non-competitive antagonists on the dose-response curve?
- shift curve to right
- reduces response (maximal response)
- cannot be overcome with more agonist
In what is the response elicited with each dose of drug described in terms of the cumulative percentage of subjects exhibiting a defined all-or-none effect, plotted against the log dose of the drug?
Quantal Dose-Effect Curves
What is the ED50? 1. The TD50? 2. The LD50? 3
- median effective dose, 50% of subjects get observed effect
- median toxic dose, 50% of animals get particular toxic effect
- median lethal dose, 50% of animals die
What is the ratio of the median lethal dose (LD50) and the ED50?
TI
What is the ratio between the dose that is lethal in 1% of the subjects (LD1) and the dose that produces a therapeutic effect in 99% of subjects (ED99)?
CSF
What is a drug response that is infrequently observed in most patients due to differences in metabolism or allergies?
Idiosyncratic drug response
What is it called when the effect of a given dose diminished?
Hyporeaction
What is it called when the effect of a given dose increased compared with the effect seen in most individuals?
hyperreactive
What is it called when drug responsiveness decreases with continued drug administration?
tolerance
What is it called when drug responsiveness diminishes rapidly?
tachyphylaxis
What is a description of molecular events initiated with the ligand binding and ending with a physiologic effect called?
signal transduction pathway
What do G-protein-coupled receptors that activate an inhibitory Galpha subunit alter activity of adenylyl cyclase to?
decrease production of cAMP
What determines the drug potency on a log dose-response plot?
position of the curve along the log-dose axis
