Week 1 Flashcards
What is the Law of Mass Action?
That the rate of a chemical reaction is proportional to the product concentration of the reactants raised to their respective coefficients
What is the affinity constant (Kd)?
The affinity constant is a measure of the strength of binding between a ligand and its receptor or binding partner in a specific interaction.
It is given by K+1 / K-1, its units at L/mol
Its reciprocal is in better units so that is more commonly used (mol/L)
What does the Equilibrium Dissociation Constant (Ka) represent?
It is numerically equal to the amount of drug required to occupy 50% of receptor sites at equilibrium.
It is characteristic of the drug and receptor
What are the axis on a Scatchard plot and what can be calculated from the line?
Amount Bound (B) / Ligand concentration on the y-axis and just amount bound (B) on the x
What actually is the Scatchard plot?
It is a graphical representation used in pharmacology to analyse the characteristics of a specific ligand-receptor interaction
In relation to a Scatchard plot, what is Bmax?
Bmax refers to the maximum binding capacity of a receptor system / the total number of available binding sites for a specific ligand on the receptor molecules
In relation to a Scatchard plot The X-intercept is the Bmax
What is the Hill equation and what does it tell us?
P(ar) = [A]/[A] + K(a)
P(ar) = Proportion of OCCUPIED receptors
K(a) = Dissociation constant
We can use individual rate constants to define an equilibrium constant:
K(a) = K-1/K+1
What does this mean?
K+1 and K-1 refer to the rate constants of the forward and backward reaction of a receptor ligand equilibrium
What is Efficacy
An empirical measure of ‘how well’ an agonist can activate its receptor
What did Stephenson postulate?
The stimulus produced by an agonist was proportional to the occupancy of receptor population AND the efficacy of the agonist
What is EC50?
EC50 is an equilibrium constant that depends on both affinity and efficacy.
EC50 = The concentration required to produce 50% response
What is the Del Castillo and Katz Equation when solved for P(ar)*?
P(ar)* = Pmax x [A] / EC50 +[A]
P(ar) = Activated ligand-receptor complex
Pmax = Maximum response
How can you calculate a) Pmax
b) EC50
a) Pmax = E / 1+ E
b) EC50 = K / 1+ E
E = Conc of enzyme
What is the Gaddum equation and what does it tell us?
EC50 / Kb = [A] / [A] + Ka
It describes:
- The relationship between the potency of competitive antagonists
- The concentration of both the agonist and antagonist
What is the purpose of the Gaddum equation? (think practical)
To quantitatively assessing and comparing the effects of competitive antagonists on agonist-induced responses
What is the point of the Schild equation?
What does it tell us?
Extra point for the big advantage of it?
The Schild equation is a tool used to characterise the potency and mechanism of action of competitive antagonists at specific receptors
It tells us:
- Whether an antagonist is competitive
- Gives the dissociation constant
Big advantage = It does NOT rely on any knowledge of the mechanism of the specific agonist receptor complex
What is the actual Schild Equation?
r - 1 = [B] / Kb
Kb = Equilibrium dissociation constant of the antagonist-receptor complex. In other words, the concentration of antagonist at which half maximal inhibition of the agonists effect occurs
r = dose ratio
How do you do Schild analysis? (think practical)
- Agonist response curve
- Incrementally increase concentration of antagonist present
- Fit dose response curves with the Hill equation (agonist concentration needed for 50% response)
a) How do you make a Schild plot?
b) How can you tell if the Schild equation applies to the data?
c) What does the X-intercept refer to?
a - Results from plotting the log of (r-1) against the log of [B]
b - Slope = 1
c - Log Kb
Schild introduced the pA2 scale. What is this?
pAx = -log(Kb)
It refers to the negative log of the antagonist concentration that produces a two-fold shift in the concentration-response curve of the agonist, resulting in a doubling of the EC50 value
It is a purely empirical measure
Why is the membrane potential a thing?
- Uneven distribution of ions inside/outside of the cells
The equilibrium potential of a specific ion is dependent on 4 things… what are they?
- Concentration of the ion inside and outside of the cell
- Temperature
- Valency of the ion
- Energy needed to separate a quantity of charge
What can the Nernst equation determine?
It determines the equilibrium potential of individual ions
Classic Q:
Describe the mechanism of the action potential
- Na+ channels are sensitive to changes in voltage
- Depolarisation causes Na+ channels to open
- Na+ ions move down their concentration gradient into the cell
- After a delay, K+ channels begin to open causing repolarisation (K+ moving out the cell)
- Na+ channels begin to be inactivated (absolute refractory period
- K+ channels slow to close = hyperpolarisation
