LEC 25 Mechanisms of Drug Action Flashcards
Why are drugs with weaker binding forces more selective?
The weaker binding forces means that the drug must be a very close fit to the receptor ie it is more selective toward the receptors it will bind
What are the specific binding characteristics between a drug and a receptor?
- Sensitivity
- Selectivity
- Specificity
- Saturability
- Reversibility
What is the Hill equation?
The graphical representation of the relationships demonstrated by Hill equation is called what kind of curve?
Graded Dose-Response Curve
Drugs that produce an effect are called what?
Agonists
What two parameters can be determined from a dose-response curve?
- Potency (ED50)
- Maximal Effect of a Drug (Emax)
What is potency?
ED50 - the amount of drug that produces half of the maximal effect
What is efficacy?
Emax - the maximal effect produced by a drug
In practice, the dose [D] in a graded dose-response curve is usually plotted on a log scale. This produces what kind of curve?
Why is this better?
Sigmoidal
Makes Emax easier to determine
Differentiate between Kd and ED50.
- Kd is associated with the receptors. It is a measure of affinity for the drug. It is when 1/2 of the receptors are activated (which is usually half of Emax).
- ED50 is a measure of potency of the drug or how well the drug activates a receptor to produce a response
Both are the x axis value at 50% of Emax; same value, but diff meaning
When comparing 2 drugs (A & B), drug A has a lower ED50 than drug B. What does this tell us about A’s potency relative to B
Drug A is MORE POTENT than Drug B
Lower ED50 means more potent
What is a partial agonist?
a drug that binds the receptor and produces a different conformational change that is NOT as efficacious at activating the signalling pathway as a full agonist (“partial response”)
a drug that produces an effect but its Emax is less than full agonist
What kind of data is plotted on quantal dose-response curves?
- plot quantal responses in a population
- “yes or no outcomes”
- Percentage of population showing some defined effect
How do we use a quantal dose effect curve to compare potency for both therapeutic and toxic/lethal effect of a drug?
- Both therapeutic and toxic/lethal responses are plotted on the same graph using different curves
- Compare the ED50 and TD50/LD50
How is the therapeutic index (TI) calculated?
=LD50/ED50
ideally, this should be a large number and will always be greater than 1
