Exam 2 Material Flashcards
Science of interactions of chemical compounds with biological systems, how and where drugs act
Pharmacology
Study of biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of their actions and effects with their chemical structure
Pharmacodynamics
The study of absorption, distribution, biotransformation, and elimination of xenobiotics
Pharmacokinetics
Characteristics of drugs
Defined by actions, most act on receptors
Endogenous drugs
foreign to the body, include toxins/poisons
Where endogenous ligands bind
orthosteric site
Receptor where gastric acid is neutralized by antacids
Extracellular receptor
Receptor used to treat infections, cancer therapy, hormones like estrogen
Intracellular receptor
Receptor of acetylcholine, muscarinic, nicotinic, GF receptors
Cell surface receptor
Drug that binds to a receptor and stimulates a biological response
Agonist
Drug that binds to a receptor without altering receptor function, alters interaction of receptor with another drug
Antagonist
Drug must achieve adequate concentrations at site of action to produce characteristic effect
Purpose of drug therapy
T/F No drug has a single effect
True
KD measures
Affinity, determines potency
Lower KD means
Higher affinity
Cheng Prusoff
Ki = IC50/[1+L/KD]
Total number of receptors on given cell or tissue
Bmax
Affinity of ligand for the receptor identified at 1/2 Bmax
KD
DOR,KOR,MOR question
Most selective for DOR - low ki value for DOR, high for MOR and KOR
Least selective - close values of ki for DOR, MOR, and KOR
Binding of an agonist results in
induced fit that activates the receptor
Binding of an antagonist results in
An induced fit that does not activate the receptor
Dose response curve for agonist
Highest
Dose response curve for antagonist
Zero
Dose response curve for inverse agonist
negative
Potency on graph
Farthest left on graph
Efficacy on graph
Height on graph, limited by toxicity
Produces a reduced response even at full receptor occupancy, can’t produce same effect as full agonist regardless of concentration
Partial agonist
Inverse agonist binds to
Orthosteric site
Competitive antagonism on graph
Lines same shape spaced apart
How to reverse competitive antagonism
Increase dose
Schild plot determines
Affinity of agonist or receptor
Non competitive agonist on graph
Lines different heights same starting point
Non competitive agonist increases ____ an decreases ___
KD, Emax
When the max response can be elicited by an agonist that does not result in 100% occupancy
Spare receptor
Functional antagonism
Two drugs influence a physiological system in opposite directions
ex - histamine and epinephrine
Chemical antagonism
Chemical reaction between agonist and antagonist that forms inactive product
Allosteric ligand benefit in therapy
ceiling effect, increased specificity for receptors with similar orthosteric binding sites
Ki value table problems
Ki = 50% occupied
Divide by 10 is 10% occupancy
multiply by 10 is 90% occupancy
Men who studied GPCRs
Lefkowits and Brian kobilka
G protein effectors
Channels, enzymes, regulatory proteins
G protein subtypes/second messengers
Cyclic AMP, Ca2+, Phosphoisinotides
Quantal log dose response
All or none, increasing curve, ED50, LD50, or TD50
Graded log dose response
Increases with increasing concentration, progressive increase, ED50 or TD50, S shaped with center symmetry
Allows comparison of drugs with similar properties
Calculate therapeutic indec
LD50/ED50, larger ratio= greater safety
Drug tolerance
Decreased responsiveness to a drug
Cross tolerance
Tolerance develops to one drug seen with drugs belonging to the same class
Tachyphylaxis
Acute development of tolerance following rapid or repeated administration, can’t overcome with increased dose
Behavioral sensitization
Increased effect of drug the more times its administered
Idiosyncratic reaction
Genetically determined abnormal reactivity to a drug, sensitive to low doses or not sensitive to high doses
Physiological variables
Age, Gender, Pregnancy, Food, Circadian Clock
Pathological factors
Liver disease, Renal disease, Malnutrition
Genetic factors
Pseudocholinesterase deficiency, malignant hyperthermia
