Drug Receptors and Pharmacodynamics

Question 1

Define receptor

Answer 1

• Proteins (usually) on a cell membrane, transmembrane receptors
• Bind ligands
• Involved in signal transduction

Question 2

Ligand

Answer 2

a molecule that is a drug, hormone, neurotransmitter that bind to a receptor

Question 3

Drug-receptor complex

Answer 3

the receptor and ligand together, initiate changes in the activity of the cell via signal transduction

Question 4

Signal transduction/cascades

Answer 4

conversion of external signal into internal signal

Question 5

Ligand-gated channels

Answer 5

i. Regulate the flow of ions through plasma membranes
ii. Activated by a ligand
iii. Binding of ligand causes conformational change in receptor, allows ions to travel through channel

Question 6

Enzyme linked receptors

Answer 6

i. Linked to enzyme in cell
ii. Made up of subunits
iii. When ligand binds, subunits fuse in conformational change
iv. Activated receptor phosphorylates tyrosine kinase → downstream signal
v. Ex insulin

Question 7

G-protein linked receptor

Answer 7

i. Largest group
ii. Large, folded, transmembrane polypeptide
iii. Contains a G protein in plasma membrane near receptor which interacts w/ GDP and GTP
v. When ligand binds, activates g protein and GTP binds alpha subunit – activated G protein can lead to cascade of reactions:
1. Secretion of substances from cell
2. Ion channels open
3. Transcription

Question 8

Intracellular receptors

Answer 8

i. Ligand is lipid soluble, passes through cell membrane
Ex. Corticosteroids
iii. Bind intracellular receptors in cytosol
iv. Ligand-receptor complex into nuclear membrane where binds with DNA to produce mRNA which produces proteins
vi. Actions:
1. Transactivate: increase rate of gene expression
2. Transrepress: one protein represses the activity of another protein

Question 9

Agonist

Answer 9

drug that activates a receptor, elicits a response

Question 10

Partial agonist

Answer 10

produces lower response when it occupies the receptor

Question 11

Antagonist

Answer 11

drug binds to receptor and prevents activation of receptor. Reduce the effects of agonists (another drug or endogenous substance) that usually activate that receptor

Question 12

Competitive antagonist

Answer 12

drug binds to same receptor as agonist; Reversible, weak, short duration

Question 13

Noncompetitive antagonist

Answer 13

Drug binds receptor at site different from the agonist binding site:
• Usually (nearly) irreversible
• Effects cannot be overcome by adding more agonist
• Effect is long-lasting, dependent on turnover rate of receptor molecule

Question 14

Chemical antagonist

Answer 14

drug directly binds an agonist, deactivating it; Ex: antacids neutralize gastric acid

Question 15

Physiologic antagonist

Answer 15

drug has opposite effect through diff physiologic pathway; Ex: . Insulin and glucagon. Overcome insulin’s effects by adding glucagon

Question 16

Down regulation

Answer 16

Type of desensitization; Ligand binding accelerates endocytosis of receptors. Then degraded and rebuilt. When process occurs faster than receptor synthesis, run out of receptors and cell can’t bind ligands

Question 17

Desensitization (aka tolerance)

Answer 17

o Common with agonists
o Attenuation of drug’s effects over time even in continued presence of agonist.
o Often rapidly reversible, second agonist response after termination of first exposure will result in similar response as initial

Question 18

Potency

Answer 18

o Concentration of drug needed to produce 50% of drug’s max effect
o Used to differentiate between agonists that have variable affinity for a receptor.
• More potent if produces effect at a lower concentration

Question 19

Dose response curve

Answer 19

o X axis: concentration of drug
o Y axis: response
o Might have 2 curves on one graph to represent desired effect vs. toxic effect at higher dose

Question 20

Efficacy

Answer 20

greatest response at a dose. How well it works

Question 21

Therapeutic index

Answer 21

ratio that compares blood concentration at which drug is toxic vs. effective
o Large TI, safer the drug.

Question 22

Therapeutic window

Answer 22

dosage range between minimal therapeutic dose and max toxic dose

Question 23

Tolerance

Answer 23

same as desensitization

Question 24

Tachyphylaxis

Answer 24

sudden onset of drug tolerance that is not dose dependent