Exam 1 Ch 2 & 3 Drug Receptors & Pharmacodynamics

Question 1

What is tachyphylaxis?

Answer 1

When responsiveness diminishes rapidly after administration of a drug

Question 2

What is one major mechanism by which tumor cells develop resistance to anti-cancer drugs?

Answer 2

Up-regulation of multidrug resistance (MDR) gene-enconded transporter expression

Question 3

What is a target molecule in the biologic system that plays a regulatory role and interacts with a drugs and initiates a chain of events leading to drug’s observed effects?

Answer 3

Receptor

Question 4

What is any substance that brings about a change in biologic function through its chemical actions?

Answer 4

Drug

Question 5

What are the three things that receptors generally do?

Answer 5

1. Determine the quantitative relation between dose or concentration of drug and pharmacologic effects through receptor affinity and total number of receptors.
2. Responsible for selectivity of drug action due to molecular size, shape, and electrical charge of drug
3. Mediate the actions of pharmacologic agonists and antagonists

Question 6

List the type of drug receptors.

Answer 6

Transport Proteins
Orphan receptors
Regulatory proteins
Structural Proteins
Enzymes

Mnemonic: TORSE

Question 7

What do regulatory protein drug receptors do?

Answer 7

Mediate actions of endogenous ligands

Ex: Neurotransmitters, hormones

Question 8

What is an example of enzyme drug receptors?

Answer 8

Dihydrofolate reductase is the receptor for the antineoplastic dug methotrexate

Question 9

What is an example of a transport protein drug receptor?

Answer 9

Na+/K+ - ATPase is a membrane receptor for cardioactive digitalis glycosides

Question 10

what is an example of a structural protein drug receptor?

Answer 10

Tubulin is the receptor for colchicine, which is an anti-inflammatory agent

Question 11

What is an example of an orphan drug receptor?

Answer 11

Ligands presently unknown

Question 12

What is an agonist?

Answer 12

A compound that binds to a receptor and produces the biologic response by activating the receptor

Question 13

What is an antagonist?

Answer 13

A compound that binds to a receptor, but does not activate generation of a signal. It also interferes with the agonist’s ability to activate the receptor. They do not have any effect on their own.

Question 14

What is a Physiologic Antagonist?

Answer 14

A drug that counters the effects of another by binding to a different receptor and causing opposing effects

Question 15

What is a Chemical Antagonist?

Answer 15

A drug that counters the effects of another by binding the agonist drug (not the receptor)

Question 16

What is a Competitive Antagonist?

Answer 16

Maximal effect reached, but at higher does of agonist

Question 17

What is a Non-competitive antagonist?

Answer 17

Reduced maximal effect even at high doses

It is irreversible and allosteric

Question 18

What does a partial agonist produce?

Answer 18

Produces that biologic response but cannot produces 100% of he response even at high does

Question 19

What does the Inverse agonist do?

Answer 19

Have the opposite effects form a full agonist.

Decrease the effects of the receptor

Question 20

What does coupling mean when talking about drugs?

Answer 20

Overall transduction process that links drug occupancy of receptors and pharmacologic response

Question 21

What are spare receptors?

Answer 21

AKA receptor reserve
Receptors are saidn to be “spare” for a given pharmacologic response if it is possible to elicit a maximal biology response at a concentration of agonist that does not result in occupancy of all of the available receptors

Question 22

What happens after an agonist occupies a receptor?

Answer 22

A conformational change in the receptor protein occurs

Question 23

When an agonist occupies a receptor, a conformational change in receptor protein occurs. What happens next?

Answer 23

Receptor Activation occurs

Question 24

When an agonist occupies a receptor, a conformational change in a receptor protein occurs, which results in receptor activation. What does this process start?

Answer 24

The beginning of many steps to produce biologic response.

Question 25

List the types of transmembrane receptors

Answer 25

``` Intracellular receptors Cytokine Receptors Enzyme-Linked Receptors Ligand-gated ion Channels G-protein Coupled Receptors ``` Mnemonic: ICE LG

Question 26

How do Intracellular Receptors work?

Answer 26

A lipid-soluble chemical signal crosses the plasma membrane and acts on an intracellular receptor (which may be an enzyme or a regulator of gene transcription)

Question 27

How do Enzyme-Linked Receptors work?

Answer 27

The signal binds to the extracellular domain of a transmembrane protein, thereby activating an enzymatic activity of its cytoplasmic domain

Question 28

How do Cytokine Receptors work?

Answer 28

The signal binds to the extracellular domain of a transmembrane receptor bound to a separate protein tyrosine kinase, which it activates

Question 29

How do Ligand gated ion channels work?

Answer 29

The signal binds to and directly regulates the opening of an ion channel

Question 30

How do G-protein Coupled Receptors work?

Answer 30

The signal binds to a cell-surface receptor linked to an effector enzyme by a G protein. The transmembrane receptor protein that stimulates a GTP-binding signal transducer protein (G protein), which in turn modulates production of an intracellular second messenger.

Question 31

Intracellular receptors for lipid-soluble agents are known to be what kind of receptors?

Answer 31

Gene-active receptors

Question 32

List 2 examples of lipid-soluble ligands that would bind to an intracellular receptor.

Answer 32

Steroids | Thyroid Hormone

Question 33

What is the therapeutic significance of an intracellular receptor for lipid-soluble agent?

Answer 33

Slower onset of action | Longer duration of action

Question 34

Describe the ligand-receptor transmembrane enzyme domains.

Answer 34

There are 2 domains that are connected by a hydrophobic segment of polypeptide that crosses plasma membrane. One domain is extracellular hormone-binding domain. This domains ligands include insulin, EGF, PDGF, ANP, and TGF-Beta. The other domain is a cytoplasmic enzyme domain that my be a protein tyrosine kinase, a serine kinase, or a guanylyl cyclase.

Question 35

What occurs during downregulation? How do you get downregulation? What is an example?

Answer 35

The ligand binding triggers accelerated endocytosis of receptors from cell surface. The receptors and bound ligands are degraded. When this process occurs at a faster rate than de novo synthesis of receptors, you get downregulation. The cell's responsiveness to the ligand is diminished. EX: EGF receptor tyrosine kinase

Question 36

What do cytokine receptors respond to?

Answer 36

Respond to heterogenrous group of peptide ligands like growth hormone, erythropoietin, interferons, etc.

Question 37

What are cytokine receptors similar to and why is it different?

Answer 37

Very similar to receptor tyrosine kinases Protein tyrosine kinase activity is not intrinsic to this receptor molecule, meaning it does not have intrinsic enzymatic activity.

Question 38

Cytokine receptors have separate protein tyrosine kinase from what family and has what kind of binding?

Answer 38

Separate protein tyrosine kinase from the Janus-kinase (JAK) family binds noncovalently to the receptor

Question 39

What do ligand and voltage-gated ion channels regulate?

Answer 39

Regulate the flow of ions through plasma membrane

Question 40

Describe the voltage-gated ion channels. Give examples.

Answer 40

Do not bind neurotransmitter directly Controlled by membrane potential EX: Verapamil inhibits voltage-gated calcium channels in the heart and vascular smooth muscle. It is a calcium channel blocker.

Question 41

Describe the Ligand-gated Channel. Give an example of a ligand-gated channel.

Answer 41

Increased transmembrane conductance of the relevant ion thus altering electrical potential across the membrane Ex: Acetylcholine binding to nicotonic acetylcholine receptor (nAChR) allows Na+ to flow down concentration gradient into cells causing deplorarization.

Question 42

Name some examples of ligands for the ligand-gated ion channels. What kind of ligands are the examples?

Answer 42

Endogenous ligands include: | Acetylcholine, serotonin, GABA, and glutamate