WEEK 1 - PHARMACOLOGY Flashcards
List the target sites for drug action
- Enzymes (e.g. ACE inhibitors, aspirin, neostigmine)
- Carrier Molecules (e.g. flavonoid – Pgp antagonist, digoxin)
- Ion channels (e.g. verapamil - L-type calcium channel antagonist)
- Receptors (e.g. benzodiazepine – GABA receptor agonist, adrenoceptor agonists and antagonists )
- Structural proteins (e.g. Taxol – Tubulin “agonist”)
- DNA (e.g. anti cancer agents like Doxorubicin)
What are receptors?
Protein molecules whose function is to recognise and respond to endogenous chemical signals.
What is meant by dose-response curve?
Dose response curves are typically used to plot the concentration of a drug (usually log) against its “response”
What is an agonist?
Molecule/drug that binds and activates the receptor
What is an affinity?
The tendency of a drug to bind to the receptor
What is Efficacy?
The tendency of a drug to activate the receptor once bound.
What is the difference between a partial agonist and a full agonist?
- If the activation is 100%, namely each time a drug interacts with its target there is a response then the agonist is said to be a “full agonist”
- If the activation is <100%, the agonist is said “partial agonist”. Partial agonists have lower efficacy than full agonists – even with maximal occupancy of receptors.
What is EC50?
Effective concentration. The dose required for an individual to experience 50% of the maximal effect
What is ED50?
Effective dose. The dose for 50% of the population to obtain the therapeutic effect.
What is Potency?
Amount of drug required to produce 50% of its maximal effects.
What is Efficacy?
The maximum therapeutic response that a drug can produce (example: morphine vs buprenorphine)
What is specificity?
Describes the capacity of a drug to cause a particular action in a population
What is Selectivity?
Relates to a drugs ability to target only a selective population i.e. cell/tissue/ signalling pathway, protein etc in preference to others.
What is an antagonist?
Molecule/drug that binds a receptor without activation
What are the main types of antagonism?
- Competitive
- Non-competitive
- Irreversible
What is competitive antagonism - describe this?
- Competitive agonists compete with agonists for the receptor binding site.
- The chemical structure of the agonist and competitive antagonist are often similar (lock and key hypothesis).
- Antagonist binds to receptor in such a way as to prevent agonist binding
- Competitive antagonism is surmountable – additional agonist can overcome the receptor blockade.
What effects does a competitive antagonist have on a dose-response curve?
Addition of a competitive antagonist shifts the dose response curve of the agonist to the right
What is non-competitive antagonism - describe this?
Non-competitive antagonists either bind to a different receptor site
OR
Block the chain of events “post” binding - acting “downstream” of the receptor.
What is irreversible antagonism - describe this?
- Antagonist dissociates from the receptor only very slowly or not at all.
- The antagonist forms covalent bonds with the receptor.
- Irreversible antagonism is insurmountable – additional agonist cannot overcome the receptor blockade.
What is an Inverse agonist?
Drug that reduces the activation of a receptor with constitutive activity (example: GABAA receptor)
Can be regarded as drugs with negative efficacy.
What is IC50 and what is it used for?
- Concentration of antagonist to inhibit 50% of the agonist maximal effect.
- Used to measure antagonist drug potency.
What is Tachyphylaxis (“rapid protection”)?
Reduction in drug tolerance which develops after a short period of repeated dosing (decrease in response). Not common. Often due to a lack of a co-factor.
What is Self-Antagonism?
When a drug becomes antagonistic to its own effects
What are Drug-drug interactions?
“Altered pharmacologic response to one drug caused by the presence of a second drug”