Introduction to Pharmacodynamics Flashcards
Which regulatory protein families are drug receptors?
- Enzymes
- Carrier molecules (transporters)
- Ion channels
- Neurotransmitter, hormone or local hormone receptors
Which receptors are the targets of NSAIDs?
Enzymes
Which type of channel is depicted?
How is this type of channel activated?
Ligand-gated ion channel.
Activated by changes in emmbrane potential or ionic concentration within the cell, causing intracellular effects.
Which type of channel is depicted?
How is this type of channel activated?
G protein-coupled receptor.
Activated by protein phosphorylation, causing intracellular effects.
They translate signal from the outside to the inside of the cell by a cascading reaction.
Which type of channel is depicted?
How is this type of channel activated?
Enzyme-linked receptor.
Activated by protein and receptor phosphorylation, causing intracellular effects.
Which type of channel is depicted?
How is this type of channel activated?
Intracellular receptor.
Activated by protein phosphorylation and altered gene expression, causing intracellular effects.
What are receptors?
Specialised, localised proteins whose role it is to recognise stimulants and translate this event into an activation of the cell.
Describe the interaction between drug and receptor.
Loose and freely reversible and does not invlove strong chemical bonds.
Describe the relationship between the chemical structure of agonist and antagonist.
- Both bind the same receptor, so there must be chemical similarities.
- One activates the receptor, the other does not, so there must be chemical differences.
What is the law of mass action?
The rate of a chemical reaction is proportional to the product of the concentration of the reactants.
K1
{A} + {B} ⇋ {AB}
K2
Describe the law of mass action applied to pharmacology.
- {D} is the concentration of the drug
- {R} is the concentration of receptors
- {DR} is the concentration of occupied receptors
- K1 is the rate constant for associations
- K2 is the rate constant for dissociations
The law of mass action basically says that by increasing the concentration of a drug, there is a greater drug-receptor interaction.
What is the equilibrium dissociation constant?
Equilibrium when rate of associations = rate of dissociations.
It represents the concentration of drug required to occupy 50% of the receptors at equilibrium.
It is a measure of the affinity of any one drug for a receptor. It is different for every drug.
What is the pD2 for an agonist?
It is conventional to express the equilibrium dissociation constant as -log10 of the dissociation constant. This is called the pD2 for an agonist.
pD2 is the -log10 of the drug that occupies 50% of receptors at equilibrium.
Describe efficacy
The ability to produce an outcome.
The maximum response of a tissue can be obtained by occupying less than 100% of the receptors.
Different drugs have different capacities to initiate a response.
A maximum response is achieved when a particular stimulus is generated by receptor occupation.
Describe this reaction
This reaction represents efficacy.
- D - drug
- R - receptor
- DR - occupied receptor
- K1 - rate constant of associations
- K2 - rate constant for dissociations
- α - rate constant of receptor inactivation
- β - rate constant of receptor activation
What are partial agonists?
Partial agonists can reduce the response to a full agonist because some receptors will be occupied by partial agonist molecules, giving a smaller response than if all the receptors were occupies by full agonist molecules.
Describe competative antagonism.
The antagonist competes for the same position on the receptor.
A true antagonist will have no efficacy, but will only occupy the active site of the receptor without causing any conformational change.
Describe allosteric binding sites.
Regulatory, not active binding sites.
They can modify the affinity or efficacy of a receptor’s endogenous ligand or drug.
Can potentiate or inhibit.
What is irreversible competative antagonism?
Antagonist binds, produces no response, but permanently blocks binding of the agonist.
Draw a graph representing antagonist classification.
Describe the action of an inverse agonist.
Receptors have background noise constantly and the inverse agonist turns this off.
It is not an antagonist because it does induce a change in the receptor.
It is possible to introduce a competative agonist for the inverse agonist.
What is a quantal dose response curve?
A graph showing the theraputic, toxic and lethal dose required for effectiveness in 50% of the population.
