Pharmacodynamics Flashcards
How does a drug exert its effects?
By binding to a target receptor
What proportion of targets do G protein-coupled receptors account for?
30%
List the order of molarity starting with picomolar.
Picomolar Nanomolar Micromolar Millimolar Molar
Define what a ligand is.
A molecule that binds specifically to a receptor
How does an agonist act at a receptor?
An agonist activates a receptor
How many moles is 1 micromolar?
10-6 M
How do antagonists function?
They block the binding site of endogenous molecules, meaning the receptor cannot be activated
Define the term efficacy.
A molecules efficacy is its ability to evoke a response in the cell its acting on
Do antagonists have any affinity and/or efficacy?
Antagonists have affinity as they can bind their target, but they have no efficacy, as they do not evoke any response in the cell
Do agonists have any affinity and/or efficacy?
Agonists have affinity as they bind their target, and they have efficacy, as their binding evokes a response in the cellular target
How can you measure drug-receptor interactions by binding?
By measuring the binding of a radioligand, which you can measure
How are high affinity drugs pharmacologically useful?
You will not need a high amount of the drug as its affinity for its target is already high
What is Bmax? What is Emax?
Bmax is the number of molecules that lead to maximal binding, while Emax is the number of molecules that lead to a maximal effect
What is the difference between concentration and dose?
Concentration is the amount of drug given to a known site of action, while dose is the concentration of drug given to a site of unknown action
What is the EC50?
The EC50 is a measure of the effective concentration of a ligand that gives 50% of the maximal response/effect - the EC50 is a measure of potency
Other than affinity and intrinsic efficacy, what else might affect a molecules potency (EC50)?
The number of receptors a cell contains
What are receptors termed that are bound by their ligand but have no effect on a ligands efficacy within the cell?
Spare receptors
Other than affinity and intrinsic efficacy, what else might affect a molecules potency (EC50)?
The number of receptors a cell contains
What are receptors termed that are bound by their ligand but have no effect on a ligands efficacy within the cell?
Spare receptors
What receptors are the therapeutic target in asthma? What does binding cause?
B2-adrenoreceptors - binding of an agonist causes relaxation
Describe the mechanism of action of salbutamol.
Salbutamol acts as a B2 adrenoreceptor agonist - it stimulates a G protein cascade through adenyl cyclase to increase levels of cAMP, activating protein kinase A - this leads to a series of events which leads to bronchodilation, widening the bronchial passages
What is the difference between a partial agonist and a full agonist?
A partial agonist has less efficacy than a full agonist
What is the role of spare receptors?
They increase sensitivity
What happens to spare receptors when a cell is over-stimulated?
The cell will remove receptors from its surface if over-stimulated - the cell is therefore less sensitive as a higher concentration will need to bind in order to bring about a response - this is seen in drug addiction
What happens respectively to receptor number in low activity and high activity?
In low activity receptor numbers generally tend to increase (receptors are up-regulated), while in high activity receptor numbers are generally decreased (they are down-regulated)
What is down-regulation of receptors (due to over-stimulation) otherwise called in drug addicts?
Tolerance
What is withdrawal/abstinence syndrome?
Neonatal abstinence withdrawal syndrome results from the cessation of the administration of drugs by the mother - this may lead to the child experience withdrawal symptoms as if they had been taking the drug themselves
List 3 examples where a partial agonist may be relevant?
- due to an absence/low levels of an endogenous ligand
- when concentrations/doses of a full agonist are too high (acting as an antagonist)
- to induce a more specifically controlled response
Give an example of a partial agonist. What receptors are their target?
Opioids are partial agonists - these usually target u-opioid receptors
What are the effects of opioids?
Pain relief
Euphoria
Respiratory depression (leading to death)
If a heroin addict injects buprenorphine, why will he/she immediately become ill? What does this say about the affinity of the 2 substances?
Buprenorphine (a partial agonist) will act as an antagonist - this antagonism will lead to withdrawal symptoms and as such the individual will feel ill - buprenorphine has a higher affinity to u-opioid receptors than heroin
How can you change a partial agonist into a full agonist?
Increasing the receptor number, meaning more partial agonists will bind and produce greater efficacy (check)
List 3 types of antagonism.
- reversible competitive antagonism
- irreversible competitive antagonism
- non-competitive antagonism
How does increasing the concentration of a reversible competitive antagonist affect an agonist concentration-response curve?
It will shift the curve to the right
Give an example of a reversible competitive antagonist. Clinically, how may this be useful?
Naloxone - this may be used in respiratory depression after opioid overdose - it’s high affinity means it will compete effectively with other opioids
What is the IC50?
The concentration of an antagonist needed to give 50% inhibition
What is irreversible competitive antagonism?
Where the antagonist dissociates from to target slowly, or not at all
Where do non-competitive antagonists bind?
Allosteric sites of the target
How does increasing the concentration of a irreversible competitive antagonist affect an agonist concentration-response curve?
Initially it will shift it right, like a reversible competitive antagonist - at higher doses it will also decrease the maximal response (decrease the height of the curve)
What is an allosteric site?
A site on a protein other than the active site where molecules bind to either enhance or reduce the effects of an agonist
