03 - Agonists and Dose Response Curves (pharmacodynamics) Flashcards
Dose response curves are plotted using the log of the agonist dose or concentration. This usually results in:
a) bell curve
b) straight line
c) exponential curve
d) s-curve
d) s-curve
Quantal dose-response curves look at…
A population
Graded dose-response curves look at…
The response of a specific patient, tissue or system
Why plot a dose response curve (3)?
- Allows estimation of E max
- Allows estimation of ED50/EC50
- To determine efficacy and potency
In the Two-State Hypothesis, the two states are:
Rested (R) and Activated (R*)
In the Two-State Hypothesis, the tendency to form the drug-receptor complex is known as…
Affinity
In the Two-State Hypothesis, the tendency towards activation of the drug-receptor complex is known as…
Efficacy
Total binding - non-specific binding =
Specific binding
Affinity can be calculated by dividing…
K1 / K-1
A drug with a higher K1 will tend to…
Bind
A drug with a higher K-1 will tend to…
Dissociate
KD is the equilibrium…
Dissociation constant
KD is equal to the concentration of ligand at which…
50% of available receptors are occupied
A lower KD means…
a) higher affinity
b) lower affinity
c) no change to affinity
a) higher affinity
Lower KD means less ligand. If less ligand is required to bind the same number of receptors, a higher proportion of it is binding. So the ligand binds more readily, aka a higher affinity.
A graph of agonist concentration against response shows:
a) affinity
b) efficacy
c) potency
d) response mechanism
e) receptor density
c) potency
Response =/= binding
If the relationship between the occupation of receptors and the effect is linear, KD is equal to
EC50
If the maximum response (E max) occurs without all receptors being occupied a system is said to have…
Spare receptors
When considering efficacy, drugs can be divided into (2)…
Full or partial agonists
Full agonists produce maximum response while occupying…
A small percentage of receptors
When compared to full agonists, partial agonists show a…
Truncated curve (lower max response)
Dose-response curve
Name one partial agonist and why this property is useful…
- Varenidine (binds to nicotine receptors, partial response allows smokers to wean off nicotine)
- Tamoxifen (binds to estrogen receptors to treat breast cancer, partial response preserves estrogen receptors because some are still needed)
Receptors may sometimes respond to partial agonists as if they were full agonists. Receptors that do this are in…
Flip states
An inverse agonist differs from an antagonist in that…
It has an effect in addition to simply stopping agonists from binding to the receptor
Benzodiazepines bind to GABA A at the…
Allosteric site
Benzodiazepines increase:
a) Efficacy of acetylcholine
b) KA for dopamine
c) Efficacy of GABA
d) Efficacy and KA of GABA
e) Efficacy and KA of seratonin
d) Efficacy and KA of GABA
PAM stands for…
Positive Allosteric Modulation
NAM stands for…
Negative Allosteric Modulation
Positive Allosteric Modulation increases the affinity of the…
Endogenous agonist
Desensitisation of the receptors is known as…
Tachyphylaxis
Tachyphylaxis may result from (4)…
- Conformational changes
- Internalisation of receptors
- Depletion of mediators
- Altered drug metabolism
