Flashcards in Drug mechanisms and actions Deck (27)
What is a magic bullet?
A drug that has an affinity only for the intended target (molecule/ receptor) and has no affinity for normal body constituents
Give examples of drug targets and some drugs that work on them
-Enzymes: ACE inhibitors, aspririn
- Carrier molecules: digoxin
- Ion channels
- Receptors: benzodiazepine (GABA)
- Structural proteins (e.g. tubulin)
What are dose response curves?
A graph where you plot the concentration of a drug (log) against its response.
Useful to compare drugs acting at the same target to assess the affinity, efficacy and margins of safety.
Why do we use the log dose in dose response curves as opposed to linear?
Because in log it is easier to see when saturation occurs
An agonist has AFFINITY and EFFICACY causing a biological response.
-Can have full or partial agonists
What is the definition of efficacy?
The tendency of the drug to activate the receptor once it has bound
What do EC50 and ED50 stand for?
-Effective concentration: concentration at which 50% of the maximal effect is achieved
-Effective dose: Dose for 50% of the population to obtain therapeutic effect
How do you calculate the therapeutic index?
Divide the toxic dose by the effective dose
What measures can used to evaluate a drugs strength and effectiveness?
- Potency and efficacy
Amount of drug needed to produce 50% of its maximal effects
In terms of pharmacology what is the difference between specificity and selectivity?
-Selectivity relates to a drugs ability to target ONLY a selective population whereas....
-Specificity: capacity of a drug to cause an action WITHIN a population (target)
-Binds to receptor but doesn't activate it. i.e. they have affinity BUT 0 efficacy
What is competitive antagonism?
-Compete for the receptor binding site
- Structure= similar to the agonist
-Antagonist binds to receptor preventing agonist from binding
-It is SURMOUNTABLE: increasing conc of agonist can overcome it
Which way does the dose response curve shift is you add a competitive antagonist?
To the right
Describe non competitive antagonism
- They EITHER bind to a different receptor site which changes shape of the agonists binding site to it can't bind
- blocks chain of events that occurs post binding(affects signalling pathways)
What is irreversible antagonism?
-Antagonist dissociates from the receptor only very slowly or not at all.
-Antagonist forms covalent bonds with the receptor
-Irreversible antagonism = INSURMOUNTABLE
Name some irreversible enzyme inhibitors
What is meant by an inverse agonist?
A drug that reduces the activation of a receptor- have a negative efficacy.
What does IC50 mean? What is it used for?
-Concentration of antagonist to inhibit 50% of the agonists maximum effect
- Used to measure antagonist drug potency
What is Tachyphylaxis?
Reduction in drug tolerance, develops after short period of repeated dosing (i.e. drug becomes less effective)
List ways in which drug targets can become less sensitive
-Change in receptors: become resistant to drug stimulation
- Loss of receptors: endocytsosis
- Exhaustion of mediators
-Increased metabolic degredation ( high con of drug needed)
What are the potential outcomes of drug-drug interactions?
-ENHANCEMENT of one or more drugs
- Development of NEW EFFECTS
- INHIBITORY effects on one or more drugs
What are the 3 mechanisms of drug interactions?
- Pharmaceutical (related to physiochemical poperties/ formulation)
-Pharmacokinetic (related to ADME)
-Pharmacodynamic (related to interactions within receptor signalling- antagonism, synergisms)
What is meant by summation?
Two drugs administered together= the effect is equal to the sum of the individual effects of the drug (1+1=2)
What is meant by potentiation?
Drug/ food increases effect of another drug BUT has no effect when given alone (1+0=2)
What is meant by synergism?
2 drugs given together produce effects greater than would be seen if either drug given individually. (1+1=3)