Drug-Receptor Interactions

Question 1

Define: Affinity

Answer 1

strength of the physical interaction between a drug and receptor, how tightly is the drug bound to the receptor?

Question 2

Define: Specificity

Answer 2

how selective a drug binding to one type of a receptors but not others

Question 3

Define: Efficacy

Answer 3

how effective a drug is at eliciting a receptor response

Question 4

Define: Potency

Answer 4

how much of the drug is needed to produce an effect

Question 5

Describe: Radioligand Binding Assay

Answer 5

1. drug is radioactively tagged
2. radioactive ligand is placed in a vessel with receptor
3. the solution is filtered- ligand-receptor complex will remain whereas unbound ligand can be washed away
4. bound ligands will produce a light that can physically measure the chemical interaction between the drug-receptor complex

Question 6

Define: Receptor Fractional Occupancy

Answer 6

(receptor bound with drug)/ (free receptor + receptor bound with drug)

Question 7

What information can be found on a drug binding curve?

Answer 7

Kd = drug concentration when 50% of receptors bound with the drug (affinity= 1/Kd: lower the Kd, higher the affinity)

Question 8

Define: Kd

Answer 8

drug concentration when 50% of receptors bound with the drug, is used to measure affinity

Question 9

What information can be found on a dose response curve?

Answer 9

-EC50= the concentration of a drug that produces 50% of maximal response (potency: lower the EC50, higher the potency)
-maximum response= reflected by the upper limit of the curve (efficacy: higher the maximum line, higher the efficacy)

Question 10

What factors affect a drug’s clinical effectiveness?

Answer 10

-potency
-efficacy
-the ability to reach its receptors

Question 11

Define: Agonist

Answer 11

ligand that binds to a receptor and activates its signaling, shifting the equilibrium towards he active site

Question 12

Define: Antagonist

Answer 12

ligand that binds to a receptor, but does not activate signaling- does not effect the equilibrium between active and inactive state, but prevents agonist binding

Question 13

Define: Inverse Agonist

Answer 13

ligand that produces the opposite effect of the agonist, shifting the equilibrium towards the inactive state

Question 14

Define: Partial Agonist

Answer 14

ligand that produces a lower response than an agonist, shifting the equilibrium slightly towards the active state

Question 15

Describe: Chantix (varenicline)

Answer 15

nicotinic ACh receptor partial agonist that replaces nicotine (a full agonist) for smoking cessation

Question 16

Describe: Narcan (naloxone)

Answer 16

opioid receptor antagonist that has a high affinity for the receptor that treats opioid overdose with little or no symptoms by itself. IM or intranasal spray that is effective 2-5 minutes after administration

Question 17

Define: Competitive Antagonist

Answer 17

competes with the agonist for binding of the same site as agonist

Question 18

How does an agonist + competitive antagonist effect a dose binding curve?

Answer 18

maximal response does not change, but EC50 is increased- a sufficient amount of agonist can overcome a given concentration of competitive antagonist

Question 19

Define: Noncompetitive Antagonist

Answer 19

receptors can have multiple binding sites (allosteric site) so the antagonist binds to a seperate site and interferes with agonist binding or modifies receptor activity

Question 20

How does an agonist + noncompetitive antagonist effect the dose binding curve?

Answer 20

maximal response is reduced, but EC50 may or may not be changed- no amount of agonist can effect the results induced from noncompetitive antagonist

Question 21

Describe: Lock and Key Model

Answer 21

the ligand and receptor are complementary to each other

Question 22

Describe: Induced Fit Model

Answer 22

“hand and glove” model, there are conformational changes of the ligand and the receptor

Question 23

Describe: Conformational-Selection Model

Answer 23

protein receptor fluctuates among several conformational states and only some of the conformations states allow ligand binding

Question 24

What are drug targets mentioned in lecture?

Answer 24

proteins(receptors, enzymes, binding sites on ion channels) and DNA

Question 25

Define: Pharmacophore

Answer 25

minimum chemical feature necessary to elicit the biological response at a given biological target

Question 26

Define: Pharmacodynamics

Answer 26

the study of the effects of the drugs on the body, including the interaction of drugs with their biological targets

Question 27

Describe: Covalent Bonds

Answer 27

strongest bond which causes an irreversible link (for the most part…) so they seldom formed by drug-receptor interactions due to the long half life, BUT non-self cells abnormal-self cells targets may be desired

Question 28

Describe: Ionic bonding

Answer 28

strongest non-covalent bond which results from oppositely charged groups orientation does not matter

Question 29

At physiological pH, pH 7.4, what amino acids can participate in ionic bonding?

Answer 29

lysine (Lys), arginine (Arg), glutamic acid (Glu), aspartic acid (Asp)

Question 30

Describe: Ion-Dipole or Dipole-Dipole Bonding

Answer 30

weak bonding where the is an attraction between permanent dipoles on polar groups within a ligand and target molecule orientation matters

Question 31

List the relative strength of electrostatic interactions from strongest to weakest.

Answer 31

ionic bond> ion-dipole> dipole-dipole

Question 32

Describe: Hydrogen Bonding

Answer 32

a type of dipole-dipole interaction between a proton of a group, X-H ( electronegative atom, X= O, N, S) and another electronegative atom that contains an unshared pair of electrons (N, O, S, or F) orientation matters

Question 33

What are the Hydrogen Bond ACCEPTORS examples presented in class?

Answer 33

ketone, ester, ether, thioether, disubstituted amides, disubstituted carbamates, pyridines, fluorine

Question 34

What are the Hydrogen Bond DONORS examples presented in class?

Answer 34

pyrrole and protonated amine

Question 35

What are the Hydrogen Bond acceptors AND donors presented in class?

Answer 35

alcohol, phenol, amide, unionized primary and secondary amines, unionized carboxylic acid, carbamate, urea, thiol

Question 36

Describe: pi interactions

Answer 36

positively charged groups and the center face of an aromatic ring (partial negative charge)

Question 37

Describe: pi-pi interactions

Answer 37

interaction between aryl rings (benzene rings), could be T-shaped edge to face or parallel-displaced stacking (pi stacking)

Question 38

Describe: Hydrophobic Interactions

Answer 38

weak interaction that describes the tendency of nonpolar compounds (or parts of compounds) to attract other nonpolar compounds- hydrophobic pockets

Question 39

Describe: Van der Waals Attractions

Answer 39

an attraction between nonpolar portions of two molecules due to temporary dipole in a carbon-carbon covalent bond within one molecule, “induced dipole-induced dipole attraction”