Fundamental Principles of Pharmacology II Flashcards
Definition of Emax
Max effect that a drug can produce
Definition of EC50
Conc of a drug that produces 50% of the max response (umol, nmol, pmol)
Definition of transduction
A molecule binds to extracellular binding site that induces a response on the cytosidic side
Definition of affinity (Kd)
Molar con of a drug required to occupy 50% of the receptors at equilibrium
The higher the affinity, the lower the Kd
Definition of efficacy
Drug binds to the receptor and activates the receptor
Usually an agonist
Definition of partial agonist
Low efficacy, less effective
Definition of full agonist
High efficacy, very effective at producing a biological response
Definition of antagonist
Act to inhibit the effects of a NT/drug
Has affinity but doesnt activate it (no efficacy)
Definition of competitive antagonists
Compete with agnostic for same site on receptor but doesnt activate it
Definition of non competitive antagonist
Act as a different site on the receptor or another molecule closely associated with it
Definition of dose ratio
Ratio of the conc of agonist producing the same response in the presence and absence of the antagonist
Definition of pA2 (affinity of an antagonist)
-ve log of the molar conc of antagonist that necessitates that you double the agonist con to produce the same response
Describe the relationship between the drug conc and the response
What are the key 3 features of this relationship
What determines the max response
Drug conc response curve gives rectangular hyperbola
Log drug conc response curve gives a symmetrical sigmoid
At the lowest conc, no response
In the linear segment, linear relationship between drug conc and response
At the highest conc, increasing [drug] does not increase response
Max response determined by tissues or drug
What is Max and EC50 and the importance of both these values
Emax, max effect that a drug can produce
EC50, conc of drug that produces 50% of max response
Indicates the position of the curve on the conc axis
Used to quantify drug potency
Describe receptors and their functions and properties
Protein macromolecules, normally inserted across lipid bilayer of cell
2 functions
- Recognition/detection
- Trasnduction
Selectively bind to certain chemicals (hormones, NT)
Describe how drugs are classified and why specificity is important
Classified by the drugs they bind to
Drugs designed to bind specifically to a type of receptor
Leads to fewer side effects
Describe the relationship between drugs, receptors and binding
Describe what happens to the drug after it has bound to the receptor
D+R <=> DR
Binding is reversible in most drugs
Drug is not altered by the receptor, not like enzymes
Describe what affinity (KD) is and what it involves
Molar conc of drug required to occupy 50% of the receptors at equilbrium
Increased affinity, decreased Kd as fewer drug molecules needed to bind to the receptor
Receptors are continually bombarded by chemicals. Only those with affinity will bind
Drugs with a lower Kd stay bound for a long time, have a slow dissociation rate
What is the difference between affinity and efficacy
Affinity, whether drug binds to receptor
Efficacy, whether drug activates receptor (normally agonist)
After binding, agonists produce a conformational change in receptor structure
Describe how agonists work
A+R<=affinity=>AR<=efficacy=>AR*=>response
Activation of receptor => biological response
Efficacy, the ability of a drug to activate the receptor
What are the 2 types of agonist
Partial
Full
Describe partial agonists and their graph
Low efficacy, less effective
Often fail to produce a full response despite occupying all receptors
Sigmoid curve does not reach 100 % response but is very far to the R
Describe full agonists and their graph
High efficacy, v effective at producing a response
Often produce max response whilst only activating some receptors
Sigmoid curve reaches 100% response but is very far to the L
What are the 2 types of antagonists
Competitive
Non competitive
Describe how competitive antagonists work
Compete with agonist for same site at the receptor molecule
No efficacy
Can be reversible/ irreversible
Describe how non competitive antagonists work
Act at a different site on the receptor or another molecule slowly associated with it
Describe how reversible competitive antagonists work
What are 3 examples
Inhibit effect of NT/hormone
Effects overcome by increasing [agonist]
-Propanolol, Mepyramine, Pancuronium
What is the parallel shift to the right
Reversible competitive antagonists produce a parallel shift to the R
log [agonist] on x axis
Response on y axis
As the conc of agonist increases, the response increases as more antagonist is being outcompeted
However, if you increase the conc of antagonist, the curve shifts to the R so you need a greater conc of agonist to overcome the inhibition
How would you calculate antagonist affinity
Extent of shift measured with dose ratio
Dose ratio, ratio of [agonist] producing the same response in the presence and absence of antagonist
Size of shift = measure of affinity of antagonist for receptor
What is the pA2 of an antagonist
Affinity of an antagonist quantified with pA2
-log of molar conc of antagonist that necessitates that you double [agonist] to produce same response
Describe the sigmoid curves produced by irreversible competitive antagonists
Shift is not parallel so block is not surmountable
As log [agnost] increases, response decreases, curve shifts to the R and gets shorter
