Lecture 3: Pharmacodynamics Flashcards
How is Therapeutic Index calculated?
TI = TD50/ED50
TD 50: median toxic dose
ED 50: median effective dose
The ____ the TI, the safer the drug
Higher
What is drug potency?
Amount of drug required to create specific effect
-represented by ED 50
The ____ the ED 50, the more potent the drug
Lower
What is drug efficacy?
Maximal effect drug can produce
-represented by Emax
In terms of drug receptor binding, covalent bonds are irreversible/reversible?
Irreversible
-which is why most drugs bond non-covalently
Higher affinity for the drug will result in a higher or lower Kd?
Lower Kd
Lower affinity for the drug will result in a higher or lower Kd?
Higher Kd
What is drug selectivity?
Property of a drug determined by its affinities at various binding sites
How is drug selectivity measured?
Kd ratio = [Kd off target]/[Kd target]
What does a higher Kd ratio mean?
More selective drug
What is intrinsic activity?
Ability of drug to change receptor function AND produce physiological response
-only seen in agonists
What is the main difference seen in full agonists vs partial agonists?
- Intrinsic efficacy
- Activated receptors
What is pharmacologic antagonism?
Action at same receptor as endogenous ligand or agonist drug
What is chemical antagonism?
Chemical antagonist makes other drug unavailable
What is physiologic antagonism?
Between endogenous pathways regulated by different receptors
What is the difference between competitive and noncompetitive antagonists?
Competitive: Compete for binding site of receptor
Non-competitive: Can bind to allosteric site or is irreversible (covalent bonding)
How does EC50 and Emax change in competitive antagonists?
EC 50: Increases
E max: Does not change
How does EC50 and Emax change in non-competitive antagonists?
EC 50: Does not change
E max: Decreases
How are JAK stat pathways utilize what type of receptors?
Tyrosine kinases
- growth hormone
- erythropoietin
What activates GTPase?
Phosphorylated tyrosine in cytoplasmic domain of receptor binds to RAS GTPase adaptor protein
Why are RTK signaling pathways used in drug targets?
RTK can be overstimulated and RAS GTPase is never turned on
-inhibit GTP and GF signaling
