Prinicples of pharmacology Flashcards
What is a response?
A function of the number of occupied receptors.
What are the ways of regulating cell function?
Altering membrane potential
Altering enzyme activity
Altering gene expression
How do drugs regulate cell function?
Some drugs affect function directly - e.g. tetrodotoxin, aspirin, acridine dyes.
Most drugs affect cell functions via physiological receptors.
What are the types of receptors?
Enzymes e.g. cyclooxygenase - aspirin receptor
Ion channels e.g. Ca2+ channels blocked by nifedipine, causes relaxation of blood vessels
Transporters e.g. noradrenaline transporter blocked by cocaine
Physiological receptors - for hormones, neurotransmitters, e.g. acetylcholine, histamine, insulin.
How are receptors classified?
Named according to the transmitter or hormone with which they interact.
Most transmitters or hormones interact with more than one type of receptor, protein structure underlies differences between subtypes.
How can transmitters act at more than one receptor?
ACh causes a drop in blood pressure
Atropine blocks the effect of ACh.
Increased dose of ACh causes increase in blood pressure.
Muscarine mimics ACh decrease in blood pressure and is blocked by atropine.
Nicotine mimics ACh increase in blood pressure and is not blocked by Atropine.
What are the receptor superfamilies?
Integral (ligand-gated) ion channels e.g. nicotinic receptor
G protein coupled receptors e.g. muscarinic receptor
Integral tyrosine kinases e.g. insulin receptor
Steroid receptors e.g. oestrogen receptor
Cytokine receptor e.g. prolactin receptor
What is the drug receptor equilibrium?
A + R <—> AR <—> AR* —> Effect
A = drug: agonist, antagonist
R = receptor
Affinity governs binding
AR = Drug/receptor complex
<–> = Binding and dissociation
* switches drug on, efficacy governs activation
What is the law of mass action?
Predicts the rate of a chemical reaction through the mass or amount of reactants and product.
What is the law of mass action equation?
A+R <—> AR
At equilibrium: rate of binding and dissociation are equal - Kd.
Kd is dissociation constant, measured in amount - mol per litre
What is the Kd equation?
Kd = [A][R] / [AR]
What is the equation of receptors?
For a fixed number of receptors:
[RT] = [R] + [AR]
R total
R = concentration of unbound receptor
AR = concentration of drug bound receptor.
What is occupancy?
Fraction of receptors occupied by agonist is defined by occupancy (p)
p = [AR]/[RT]
What is the Langmuir isotherm equation?
p = [A] / Kd + [A]
What is the graph for Langmuir isotherm?
occupancy y axis, up to 1
[agonist] x axis
hyperbola
see image
What is the theoretical log graph for Langmuir isotherm?
Occupancy y axis
log [agonist] x axis
sigmoidal curve - increased concentration increases occupancy until a maximum point
What is the experimental graph for log Langmuir isotherm?
Effect on y axis
log [agonist] x axis
same sigmoidal curve, indicates drug is producing effect by occupancy.
What is affinity?
Affinity of a drug for its receptor is a measure of how well it binds to the receptor.
Measured using Kd - drug dissociation constant from receptor.
What is Kd?
Kd is equal to the concentration at which at equilibrium, half the receptor population will be bound with the drug.
What is EC50?
Effective concentration to produce 50% of the maximum response.
Allows measure of potency.
What is potency?
The amount of drug required to produce a particular level of effect.
What does the graph look like for EC50?
effect on y axis
log [agonist] on x axis
EC50 is half of the effect
Emax is the maximum effect
see image
What is the relationship between drug concentration and effect?
There is a threshold needed to be reached to cause an effect.
It reaches a maximum so is saturated.
It is graded - increasing the concentration produces a sigmoidal curve.
What is the relationship between drugs A and B and effect?
A higher concentration of B is needed to produce an effect.
EC50 values allow comparison of relative potency - drug B is less potent than A.
see graph
