Drug Receptors

Question 1

What does an agonist do?

Answer 1

Produces/promotes a similar response to the intended chemical

(acts like the ligand on the target receptor)

Question 2

What does an antagonist do?

Answer 2

Blocks the effect of the ligand on the target receptor

Question 3

How can two different drugs have the same result for a patient? Example: pt with COPD and pt with Asthma, both have constricted bronchioles but two different drugs could treat them.

Answer 3

One drug (sympathetic beta2 activation) causes bronchial dilation and one drug (parasympathetic m3 antagonism) blocks constriction….both lead to the same end result of opening bronchioles

Question 4

What does pharmacology study?

Answer 4

At the receptor level, what is the mechanism of action?
Ex: Beta 2 agonist, M3 antagonist

Question 5

What does pharmacodynamics (PD) study?

Answer 5

What is the physiological effect of the drug on the body?
Ex: dilates bronchial tubes, increases HR

Question 6

What does pharmacokinetics (PK) study?

Answer 6

What does the body do to the drug?
ADME

Question 7

What does pharmacotherapy study?

Answer 7

Choosing which drug is best for the pt

Question 8

What does a modulator drug do?

Answer 8

Has both agonist and antagonist effects

Question 9

What channels have quick acting effects?

Answer 9

Ligand-gated ion channels and G protein-coupled receptors

Question 10

5 protein subunits form the _____ of a ion channel

Answer 10

Pore

Question 11

T/F a specific ion channel let ions flow in and out of a cell

Answer 11

False. Ion channels either allow ions into a cell OR out of a cell (one way flow)

Question 12

How are voltage gated ion channels activated?

Answer 12

By a charge, activation of one leads to activation of the next one and so on

Question 13

T/F Voltage gated ion channels are specific for one ion

Answer 13

True

Question 14

Voltage gated ion channels do not require a _____

Answer 14

Ligand

Question 15

Where are voltage-gated ion channels found?

Answer 15

On nerves

Question 16

What is an example of a drug that uses a voltage-gated channel?

Answer 16

Lidocaine (antagonist) it blocks voltage-gated Na+ receptors which blocks Na+ permeability

Question 17

How do ligand gated ion channels work?

Answer 17

A endogenous ligand binds to a subunit of the pore which causes the permeability of the channel and allows ions to flow through it

Question 18

What is an example of a ligand gated ion channel?

Answer 18

Nicotinic Acetylcholine Receptor. At rest, the channel is closed and no ions flow through. Acetylcholine binds to 2 of the subunits (alpha) which opens the channel and Na+ flows through (intracellularly which is down the concentration gradient) and finally initiates a muscle contraction.

Question 19

Why do people respond to drugs in different ways?

Answer 19

We all have the same subunits that make up the pores of ion channels, but there are different subtypes of the subunits which we all differ in.
Short answer: we have different receptor subtypes

Question 20

What is Dr. Stremski’s favorite ion channel?

Answer 20

GABA-A (binds to subunit which allows Cl- influx)

Question 21

What does the 5HT3 Ligand-gated channel responsible for?

Answer 21

When serotonin binds to the 5HT3 receptor, the channel opens leading to an influx of Na and K into neurons –> this causes you to puke.
*5HT-3 Anti-emetic drugs are antagonist, they bind to the receptor and block serotonin from binding = no more puking!

Question 22

What is the structure of a G-Protein Coupled Receptor? (GCPR)

Answer 22

• One long peptide chain
• Wraps in and out of the membrane 7 times
• Amino Terminal = extracellular
• Carboxyl Terminal = intracellular

Question 23

Where does a ligand bind in a G-protein coupled receptor?

Answer 23

Active site in the transmembrane region

Question 24

What do G-proteins interact with?

Answer 24

Cytoplasmic region

Question 25

What is an example of a GCPR?

Answer 25

All sympathetic NS receptors are GPCR (classified as Alpha and Beta)

Question 26

Do GPCR require a ligand to be activated?

Answer 26

Yes

Question 27

What are the three components to G-protein coupled receptors?

Answer 27

1. Ligand binds to receptor 2. Receptor triggers the activation of a G-protein 3. G-protein changes the activity of an effector element (usually an enzyme or ion channel)

Question 28

What is the role of adenyl cyclase?

Answer 28

Catalyzes the reaction of ATP --\> cAMP | (less adenyl cyclase, less cAMP)

Question 29

Migraine example (migraines occur because of vasodilation, so to reverse a migraine, you want vasoconstriction)

Answer 29

5HT-1B and 5HT-1D receptors are found in CNS and on blood vessels. Coupled to inhibitory Gi, the 5HT-1 receptors have an inhibitory effect on adenyl cyclase and reduce intra-cellular cAMP. cAMP mediates smooth muscle relaxation of large cerebral arteries --\> inhibition of cAMP leads to vasoconstriction = no more migraine! | (in short: 5HT-1B/1D inhibit adenyl cyclase, which causes a decrease in cAMP which then causes vasoconstriction of cerebral blood vessels which gets rid of a migraine)

Question 30

Which receptor is ionotropic and which is metabotropic?

Answer 30

Ion channels = ionotropic G-coupled protein channels = metabotropic (indirectly linked to ion channels through signal transduction pathways)

Question 31

Ionotropic Receptors: 5 units form a _____ which alters \_\_\_\_\_\_

Answer 31

Pore, Permeability

Question 32

Metabotropic Receptors: combined to ______ which cause synthesis of \_\_\_\_\_\_

Answer 32

G-proteins, activators

Question 33

What is the structure of Tyrosine Kinase Receptor (TKR)?

Answer 33

1. Extracellular hormone binding site 2. Cytoplasmic enzyme domaine that has multiple tyrosine AA

Question 34

Explain how a TKR is activated and the cellular response

Answer 34

1. Two inactive monomers that contain multiple tyrosine AA's 2. A ligand binds to the signal-binding site (extracellular) and the two monomers form a dimer (it is not activated) 3. ATP donates a phosphate to each tyrosine 4. The phosphorylated tyrosines activate kinases which causes a cellular response (DNA Transcription)

Question 35

In what ways can a Tyrosine Kinase Receptor's activity be inhibited?

Answer 35

1. Something can bind in place of the ligand 2. Something can alter the effects of the kinase

Question 36

How do TKRs play a roll in cancer?

Answer 36

- EGF ligand enhances cell growth and division - We stop cancer by blocking cell growth and division - Drug is an antagonist to EGF - the drug binds on the receptor so EGF cannot

Question 37

A ligand has to be \_\_\_\_\_-soluble to act on an intracellular receptor

Answer 37

Lipid

Question 38

Where specifically are intracellular receptors found?

Answer 38

Cytoplasm

Question 39

Is the effect of intracellular receptors immediate or delayed?

Answer 39

Delayed because time is required to copy DNA and make new proteins

Question 40

How long can the effects of intracellular receptors last?

Answer 40

Hours to days (even after the drug is all gone because new proteins are active for days after synthesis and slow turnover of enzymes and proteins)

Question 41

What are examples of biological lipid-soluble ligands?

Answer 41

-Steroids (corticosteroids, sex steroids, vitamin D) and thyroid hormone

Question 42

What happens when a intracellular receptor is activated?

Answer 42

Transcription and translation

Question 43

Overview of all four receptors

Answer 43

Question 44

What do glucocorticoids do?

Answer 44

**They suppress the inflammatory response (antagonist?)** **Occurs via DNA transcription** - Decrease transcription of lipid soluble and protein based inflammatory mediators - Are cytotoxic to lymphocytes (B and T) - Inhibit function of tissue macrophage in antigen processing