Section 1 Flashcards
What is pharmacology?
The study of drugs
what is pharmacodynamics?
drug effects
textbook:
the study of the detailed** mechanism of action** by which the drugs produce their pharmacologic effects.
Describe the important characteristics of a
receptor.
its binding ability, change its shape to get signal into cell and push cell to have response.
Describe the relationship between [drug], binding
to receptors and effect using a dose-response curve
on a dose response curve, the effect is the y axis and the log dose is the x axis.
compare & contrast potency and efficacy
potency is: compares the concentrations of drugs needed to get 50% of maximal effect (EC50)
efficacy is: the measure of maximal effect, you can have full and partial agonists.
What is a receptor?
something that has the affinity to bind to drugs and cause an effect.
They are macromolecules that are oftem membrane bound proteins.
High affinity
low amount of drug needed
slower ending of effect (binds tightly to receptor and is slower to end)
compare & contrast agonists and antagonists
agonists have an effect. Antagonists bind to the receptor but have no effect (on the receptor, they have an effect on the agonist). They block the effect of the agonist and shifts the dose-response curve of an agonist to the right (this is the effect of the antagonist).
an antagonist would make a flat line. antagonism is competitive.
This is how reversals work*
what does a drug as an agonist do?
activates the receptor
What law does binding follow?
The law of mass action
How do you describe the drug receptor complex?
the disociation constant (Kd) is equal to the product of the concentrations of the ligand and protein divided by the concentration of the protein ligand complex once equilibrium is reached.
Kd tells how much drug to give, small Kd less drugs to give
A drug receptor is a specialized target macromolecule that binds a drug and mediates its pharmacological action. These receptors may be enzymes, nucleic acids, or specialized membrane-bound proteins. The formation of the drug-receptor complex leads to a biological response.
What is Kd?
the measure of the affinity/potency
and it also tells you how much of the drug to give.
also is a rtio of the off rate of receptor binding to the on rate.
really low disociation constant, binds tightly
for the log dose graph
what does the straight part represent?
The straight part runs from 10-90% maximal drug effect. it is 81 fold based off law of mass action (low activity to high activity). 1 drug binding site per receptor.
two binding sites means you get a steeper curve
What is the law of mass action?
In chemistry, the law of mass action is the proposition that the rate of the chemical reaction is directly proportional to the product of the activities or concentrations of the reactants. It explains and predicts behaviors of solutions in dynamic equilibrium
What is the measure of affinity/potency?
the Kd, a smaller Kd is more potent. 50% of rectopr bound at Kd is a measure of potency.
Which is more important? Efficacy or potency?
In general, efficacy is very important. A less potent drug with high efficacy will usually produce better results than a less efficacious drug with high potency.
analgesia
and examples given
the inability to feel pain
buprenorphine: a very potent (partial) agonist at opioid receptors. has high afffinity binding (which means you can give less), binds for a long time, does not give as strong an analgesic effect as morphine.
and morphine: a less potent (full) agonist. has lower affinity binding, binds for a shorter period of time, stronger analgesic affect.
about receptors and signaling
What are the type of receptors?
mentioned in the first lecture
- Ionotropic receptors: ion channels (glutamate, GABA)
- metabotropic receptors: use G-proteins, kinases (autonomic receptors - Beta adrenergic receptors)
- Transcription factors - Alter gene expression (Steroid hormones)
What is the drug receptor complex?
the binding of the drug and its receptor.
drug effects
When does the effect happen?
after signal transduction after the drug receptor complex is made after receptor binding when the drug and recdeptor meet.
describe classes of simple signal transduction
pathways
Neurotransmitters work very rapidly through ion channels: Binding very rapid, fall off receptors very rapidly (msec)
Steroids work very slowly through protein synthesis: Take hours to days to synthesize proteins
Antibodies bind slowly (minutes), come off receptors slowly (days-weeks)
describe three situations where binding of drugs
to receptors is not proportional to drug effect.
Complex interactions:
* 1 Cascades of 2nd messengers
* 2 Spare receptors: Only need to activate a small fraction of receptors to get maximal response (Neuromuscular junction)
Tolerance/desensitization:
* 3 Previous exposure to a drug may cause decreased effects
contrast the effects of competitive and noncompetitive antagonists on the dose-response curve of an agonist
Agonists:
* Bind & activate receptor
* Get a dose-response curve
Antagonists:
* Bind & don’t activate receptor
* Flat dose-response curve by themselves
* Shift the dose-response curve of an agonist
explain the effects of partial agonists, inverse agonists etc. using a receptor model where active and inactive receptors are in equilibrium
partial agonists have a lower efficacy and a smaller curve in comparison to a full agonist and not quite as s-shaped.
inverse agonists
