Lec. 3 - Pharmacodynamics/Pharmacokinetics Flashcards
How is magnitude of drug effect generally quantified?
- large population samples
- Giving doses to individuals and recording how people respond
- plotting dose vs. % of individuals responding
What is ED50?
Dose for therapeutic effect in 50% of population
How can dose response curve help in therapeutics of drug use?
Allows to compare risks and reward of drugs.
Ex. If drug A progresses linearly from sedation to coma then death, whereas drug B asymptotically reaches anesthesia; obviously drug B will be safer overall
How can dose response curves be further elaborated for particular drugs?
Can break up into curves of different effects (ie dose-response curve for effects)
Ex. Alcohol can be broken up into…
- slowed reaction time
- ataxia
- coma
What is the threshold dose of a drug?
And ceiling?
Threshold: Smallest dose at which a response is seen
Ceiling: saturation point, no more observed effects after this point (can be thought of as maxed out receptors
How is ‘maxed out receptors’ theory of ceiling flawed?
Due to the existence of spare receptors, pretty much never will receptors actually ever be fully saturated.
Max effect can be observed even if there are inbound receptors
Describe drug affinity and what it’s effects are
Some drug have a higher affinity for a receptor (ie more likely to bind), so a smaller dose will evoke a larger reaction.
This causes a difference in efficacy
In regards to drug affinity, what are 2 types of drugs?
Full agonist (high efficacy)
Partial agonist (lower efficacy)
What are 2 therapeutic implications of partial agonist
- May have less sideffects (we can’t know)
2. Can block an overdose by blocking agonist access to receptor
What are the the 2 ways to classify an antagonist
- Competitive vs non-competitive (is allosteric)
- reversible vs irreversible
Describe the difference between competitive and non-competitive inhibitors.
How does each affect the dose-response curve?
Competitive:
-competes for same binding site
- At insanely high doses, will reduce the maximal effect (ie lower the asymptote), but generally this is not seen
- Shifts the curve to the right (ie more drug needed for same response)
Non-competitive:
-causes allosteric/conformational change in receptor, preventing or reducing signalling even if agonist binds
-does not shift curve left or right, instead reduces maximal effect (lowers asymptote)
What are the 3 response curves in terms of side effects and toxicity?
- Therapeutic effect curve
- Toxic effect curve
- Lethal effect curve
What is the therapeutic window in terms of…
I) Lethality?
II) Toxicity?
I) Distance between ED50 and LD50, needs a significant margin for safety of drug in humans. Tested in animals to infer in humans.
II) Distance between ED50 and TD50, ideally no overlap (ideal therapeutic window)
What’s the therapeutic index?
Why can it be flawed?
TI = TD50 / ED50
Can be flawed because it’s a ratio of 2 points on 2 curves, doesn’t account for slope!
What are the 2 types of outliers for dose-response curve?
Toxicity outlier -> needs a huge amount of drug in order to get desired effect
Benefit outlier -> needs only very small amounts of drug for positive effect
