Session 9 Flashcards
What do agonists and antagonists have in common?
Agonists and antagonists bind at the same target proteins
What do agonists and antagonists not have in common?
Agonists elicit a response when bound to target protein, antagonists do not elicit a response and block access to the binding site for the agonist, thus interfering with the normal response.
Adverse side effects of therapeutics are primarily caused by…?
A: Impurities in the drug formulation
B: Cheap imitation drugs
C: Binding of the active ingredient to sites other than those intended
D: Non-selective binding of the active ingredient to different receptor isoforms
E: Inhibition of endogenous molecules by the active ingredient
C: Binding of the active ingredient to sites other than those intended
Although all the answers are possible, the main cause of ADRs is the drug binding to receptors or sites other than those intended.
A 52 year old man with hypertension is started on atenolol (a beta blocker), which slows the heart rate, to help control his blood pressure. Which organs might show major adverse effects?
A: lungs, kidneys, skeletal muscle B: brain, kidneys, GI tract C: adipose tissue, lungs, gall bladder D: brain, lungs, kidney E: brain, skeletal muscle, salivary glands
B: brain, kidneys, GI tract
Although all the answers are possible, the side effects list provided with the drug list brain disturbances, urinary dysfunction and diarrhoea and constipation as being the most severe.
Define the following pharmacodynamics terms:
Affinity Efficacy EC50 Intrinsic efficacy Kd Potency
Affinity - A measure of how tightly a ligand binds to its receptor.
Efficacy - 100% efficacy (Emax) is the maximum response achievable from a drug within a particular system or tissue of the body.
EC50 - The concentration of drug that elicits half the maximal response of a full agonist.
Intrinsic efficacy - A relative measure of how effective a drug or ligand is in inducing the active conformation of the target protein. For a competitive antagonist this is zero. For a full agonist this 100%, for a partial agonist it is somewhere in between, and is usually measured ex-vivo.
Kd - The dissociation constant for the binding of a ligand to a receptor – it is 50% of Bmax the total number of receptors expressed on a cell tissue or defined preparation.
Potency - The dose of drug required to produce a specific effect of given intensity (usually the EC50) as compared to a standard reference. It is a comparative rather than an absolute expression of drug activity
and depends both affinity and efficacy.
Five drugs are being tested for their ability to prevent pain. Dose-response curves are created for each and their Emax and Kd values calculated (respectively):
Drug 1 - 10nM; 1mM Drug 2 - 100mM; 2mM Drug 3 - 10uM; 1.4mM Drug 4 - 100nM; 1.2mM Drug 5 - 1pM; 1.8mM
Based on these values: Drug ____ is the most potent drug; drug_____ has the highest affinity.
A: 5, 1 B: 2, 4 C: 3, 5 D: 5, 2 E: 4, 3
A: 5, 1
The drug with the lowest values for both efficacy and Kd will have the greatest potency and binding affinity, respectively.
A Phase 1 clinical trial for two new proton-pump inhibitors has been performed and the results of the trial are plotted on a graph of [Agonist] (m) (x-axis) against Response (y-axis)
Drug A and B both follow the same shape, but drug A is to the left of Drug B.
Which pharmacodynamics parameter does the plot show is increased by drug A with respect to
drug B?
A. Affinity B. Agonism C. Antagonism D. Efficacy E. Potency
E. Potency
This is a dose-response curve and so potency of drug A is greater than that of drug B. Their efficacies are the same and both appear to be agonists. To measure drug affinity, a binding-dose curve would need to be created.
