Pathophysiology and Drug Action Exam 2 (Set 1) Flashcards
Define pharmacology
science of interactions of chemical (drug) compounds with biological (receptor) systems
Define pharmacodynamics
the study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of their actions and effects with their chemical structure
Define pharmacokinetics
the study of the absorption, distribution, biotransformation, and elimination of xenobiotics
Describe the characteristics of drugs
-are defined by their actions (whether they are agonist or antagonist)
-act on receptors
-can be endogenous or xenobiotics
-have covalent, electrostatic, and hydrophobic interactions
-drug shape/design for receptor specificity
What do receptors mediate the actions of?
4 types of ligand that act by binding to a cell surface receptor (orthosteric)
1. agonists
2. antagonists
3. partial agonists
4. inverse agonists
Allosteric
1. positive (PAM)
2. negative (NAM)
what is an agonist?
a ligand that binds to a receptor and produces an appropriate response
what is an antagonist?
ligands which prevent an agonist from binding to a receptor and therefore prevent its effects
what is a partial agonist?
an agonist that will not produce the maximal response of which the tissue is capable, even when it binds to the same number of receptors as a full agonist binds to when it produces a complete response
-may prevent the action of pother agonists, and may appear to be acting as an antagonist
What is an inverse agonist?
compound that binds to a receptor and produces an effect opposite to that of its corresponding agonist
define and name sites of drug action
-where the acts to initiate the chain of events leading to an effect
-extracellular
neutralization of excessive gastric acid by antacids
Cholestryramine resin in reducing cholesterol absorption
-intracellular
infections; cancer chemotherapy; hormones such as estrogen
-on the cell surface
majority of drugs
acetylcholine
catecholamines
growth factors
What is the Concentration-Effect Relationship?
-measures the EC50;EC10;EC90 etc
-concentration of drug that produces 50% of the maximal response
-sigmoidal curve
relate affinity to the law of mass action
the effect of a drug is directly proportional to the amount of drug-receptor complex formed
[D][R]/[DR] = k(off)/k(on)=Kd (dissociation constant)
THE LOWER THE KD THE HIGHER THE AFFINITY
define KD
-KD concentration is reached when 50% of the drug is bound
-KD is the concentration of ligand that will bind half the receptors at steady state
relate affinity to receptor occupancy
-the relationship between occupied receptor B and drug/ligand concentration D
outline components in a receptor binding assay
-requires radiolabeled ligand
-receptor will bind to ligand
-will be filtered and just the ligands will be left (some test ligands some regular ligands)
-displays competitive binding to displace the test ligands
What is Bmax and KD in terms of saturation binding anaylsis?
Bmax is the total number of receptors on given cell or tissue
KD is affinity of ligand for the receptor readily identified at 1/2 Bmax
What is pharmacological profiling?
-heterologous competition testing several unlabeled compounds simultaneously
-can calculate rank affinity from it
How is Ki calculated?
-using the Cheng-Preusoff equation
Cheng-Prusoff: Ki= IC50/[1+L/KD]
-Ki is indirect measure of affinity (KD)
IC50 is determined experimentally
L is radio labeled drug concentration
What is Ki? What does it measure?
-dissociation constant describing the binding affinity between the inhibitor and enzyme
-measures binding affinity (potency)
-highest affinity, lowest KD found on the furthest left line on the graph
What does IC50 measure?
concentration of inhibitor required to reduce the enzymatic activity to half of the uninhibited value
WHAT IS THE CHENG PRUSOFF EQUATION?
Ki=IC50/[1+L/KD]
how does receptor affinity relate to receptor selectivity
greatest affinity does not mean greatest selectivity
greatest selectivity will be large number ex. 50 times selective for DOR over MOR or KOR
best affinity will be low number ex.0.75
What is Bmax?
-total number of receptors on a given cell or tissue
-Bmax values are independent of the ligand
-can influence downstream signaling events
