Lecture 1: Introductory Principles Flashcards
Pharmacodynamics
The branch of pharmacology concerned with effects of drugs, and the mechanism of their action. The effect of a drug on the body
Pharmacokinetic
The branch of pharmacology concerned with the movement of drugs through the body. The effect of body on a drug
Agonist
Any substance that can produce a functional response at a target site
Antagonist
A substance that stop a normal physiological response from occurring e.g. blocking neurotransmitter release
Occupancy
How much of a drug blocking receptors or recognition sites
Affinity
Ability to bind The higher the affinity the higher the occupancy
Efficacy
The functional response
Potency
The concentration of a drug needed to get an effect
What are the targets for drug action?
Receptors, Ion channels, enzymes and transporters/carrier molecules
Receptors
A recognition molecule for an endogenous chemical mediator Sensing element in the system of chemical communication that coordinates function of all different cells in body, the chemical messengers
Ion channels
Gateways in cell membrane Selectively allow passage of particular ions Ligand gated ion channel: only open when one or more agonist molecules are bound Voltage-gated channel: gated by changes in the transmembrane potential
How does drugs affect ion channel function?
Bind to channel protein itself or by indirect interaction involving a G protein A drug may directly block a pore or a drug may bind to part of an ion channel
Enzymes
Pharmacologically active drugs that can be activated by the correct enzyme in the area it needs to be activated
Transporters/carrier molecules
Transport of ions and many organic molecules across renal tubule, the intestinal epithelium and the blood brain barrier
What does activation mean?
The receptor is affected by the bound molecule and will elicit a tissue response
What does the occupation of receptors Increase?
The affinity of a drug for any target
What can agonist mimic the effect of?
Endogenous molecule
What does agonist possess?
Significant efficacy
What does antagonist have?
Zero efficacy
What does the law of mass action give rise to?
Dissociation constant
What does the law relate?
That the rate of chemical reaction is proportional to the concentration of the reacting substance
What is the dissociation constant?
A constant between free drug/free receptor concentration and drug/receptor concentration in other equation
What happens when you increase concentration of drug?
Shift equilibrium to right (elevation in drug receptor complex)
What does it mean if a drug has high affinity for its receptors?
Low dissociation constant
What is kd?
The concentration at which half of the receptors are occupied by drugs
What is high affinity of a drug for a receptor?
High occupancy of drug binding to receptor
High affinity drug
Low kd
Low affinity drug
High kd
What are key considerations for binding?
Total binding Non specific binding Specific binding
What is proportional to degree of radioactivity that can be measured within test solution?
Amount of binding you have to a receptor
How can specific binding be measured?
Substractive process
What does the binding curve define?
Relationship be ween concentration and the amount of drug bound
What does scarchard plot give?
Straight line from which the binding parameters K and Bmax can be calculated
What experiment can be used to determine efficacy and potency?
The bioassay experiment
What is an example of bioassay?
Organ bath
Why doesn’t concentration-response curve give direct estimates of affinity of drugs for receptors?
Relationship between receptor occupancy and response is usually non-linear
E-max
Measure of efficacy - the maximal response that the drug can produce
EC-50
Effective concentration that produces 50% is the maximum response - a measure of potency
Potency
A measure of drug activity, governed by both affinity and efficacy
Efficacy
The ability of a drug to cause a functional response as a result of binding to its receptor
What efficacy do partial agonists have?
Less than 1
What are full agonists?
Compounds that are able to elicit a maximal response following receptor occupation and activation
What are partial agonist?
Compounds that can activate receptors but are unable to elicit the maximal response of the receptor system
What does occupancy and affinity show?
How a drug binds to receptor
What does efficacy and potency show?
What happens when the drug is bound to receptor
What is reversible competitive antagonism?
Bind to receptors reversibly A parallel shift to the right of dose-response curve The maximum response is not depressed Both free to associate/dissociate from target site Raising the agonist concentration can restore the agonist occupancy
What is irreversible competitive antagonism?
Produces a parallel shift to the right Depresses the maximum response Effectively remove receptors
How do you quantify antagonism?
An antagonist has no efficacy Hence need a suitable agonist, the action of which can be inhibited by the antagonist of interest Antagonist potency can be expressed in the form of PA2 value
What is the PA2 value?
Negative logarithm of the molar concentration of antagonist which will reduce the response of a tissue to a double dose of agonist to that of a single dose of agonist
The schools plot
Conduct an organ bath experiment examining tissue response to an agonist in the presence of increasing concentrations of antagonist
What is the dose ratio?
Dose needed in presence of antagonist compared to dose needed with no antagonist
What are other times of antagonism?
- Chemical antagonism 2. Pharmacokinetic antagonism 3. Physiological antagonism
