2.1

Question 1

What is a receptor?

Answer 1

Specialized target macromolecule that binds drug or ligand and mediates its pharmacologic action

Question 2

What is drug specificity? How are receptors specific?

Answer 2

Have structural features that permit drug specificity
Specificity  selectivity of response
Must have both a drug-binding domain and an effector (active) domain

Question 3

What are some examples of drugs that don’t have to bind to a receptor?

Answer 3

Antacids
Osmotic Diuretics 
manitol	
Heavy Metal Chelating Agents 
EDTA(Ethylenediaminetetraacetate) – lead poisoning	
Barrier Ointments and Cream
A&D ointment, Zinc oxide ointment
Disinfectants
Chlorhexidine (hibiclens)
Alkylating anticancer agents
Cyclophosphamide

Question 4

What are soluble receptors?

Answer 4

Lipid soluble ligand  crosses cell membrane  act on intracellular receptor  in nucleus for transcription/translation

Question 5

What are examples of lipid-soluble receptors?

Answer 5

Ex: steroids, vitamin D, and thyroid hormone  stimulate the transcription of genes
Consequences:

Question 6

What are the consequences of lipid-soluble receptors?

Answer 6

Take time (at least 30min) 
Transcribe genes and synthesize new proteins  Not immediately relieve sx
The effects can persist for hours or days after the drug has long been eliminated (need to wait for the proteins these drugs encode for to be used)

Question 7

What are transmembrane receptors? How do they work? Example?

Answer 7

Drug binds to a receptor on a protein that spans the cellular membrane which starts a cascade of effects within the cell. Ex: tyrosine kinase

Question 8

How does tyrosine kinase work? Broadly? With a specific example?

Answer 8

Broadly- add a phosphate group to tyrosine

More specifically: EGF(epidermal growth factor) binds to receptor  convert from monomeric to dimeric state initiates phosphorylation of tyrosine  promote cell growth

Question 9

What are the consequences of using tyrosine kinase?

Answer 9

Target site for drug therapy
Ex: gefitinib (Iressa), erlotinib (Tarceva) – NSCLC
Inhibit receptor’s kinase activity in the cytoplasm
Inhibit cell growth

Question 10

How do ligand-gates transmembrane channels function? Common example?

Answer 10

Channel that opens when a messenger (ligand) binds to it.

Nicotinic acetylcholine (Ach) receptor
	Ach binds to the receptor 
Open Na+ channel  Na+ to rush into cell  skeletal muscle contraction

Question 11

What are the consequences of ligand-gated channels?

Answer 11

Time to response is fast; can be in milliseconds
Create important drug target (i.e. Verapamil inhibits voltage-gated calcium channels in heart and smooth muscle  antiarrhythmic effects and reducing BP

Question 12

How does a G-membrane channel work?

Answer 12

Transmembrane receptor stimulates GTP-binding signal transducer G protein  increase intracellular second messenger  signal amplified

Question 13

What is an example of a g-membane receptor?

Answer 13

Norepi  stimulates receptor  stimulates production of GTP  amplify the original signal  produce effects

Question 14

Which classes of receptors require gene transcription?

Answer 14

Tyrosine Kinase

Transmembrane diffusing nuclear receptors

Question 15

What are full and partial agonists?

Answer 15

Full Agonist – trigger a full response

Partial Agonist – trigger a “partial” response (i.e. not as pronounce as the full agonist regardless of concentration)

Question 16

What is an allosteric agonist?

Answer 16

Uses a separate active site to magnify response of agonist

Question 17

What is an inverse agonist? What needs to be present for this response to occur?

Answer 17

Receptor needs basal activity; that is, without a ligand bound it does something, so when the inverse agonist binds the signal is suppressed and theres an opposite effect

Question 18

What is a non-competitive antagonist?

Answer 18

bind to receptor equally well whether or not receptors already bound the substrate
Binding to same active site

Question 19

What is an allosteric non-competetive antagonist?

Answer 19

binding to a separate site

antagonist that doesn’t need to compete. Just turns off fxn.

Question 20

What is an un-competetive antagonist?

Answer 20

ligand binds to a receptor, THEN a new site opens up, that allows an antagonist to bind

Question 21

What is a neutral antagonist?

Answer 21

blocks the docking of the agonist but does not trigger an effect
Like a hat- blocks the receptor but doesn’t do anything

Question 22

What is efficacy?

Answer 22

Percent of maximum effect that can be achieved?

Question 23

What is potency?

Answer 23

How much is needed to trigger a given effect

Question 24

What is EC50? Why is it used?

Answer 24

The concentration of drug that produce 50% of response – use to compare potency

Question 25

What is affinity? What influences it?

Answer 25

The tendency of a drug to bind to a receptor Directly proportional to efficacy and potency Mostly influenced by the rate of dissociation (KD) i.e. the lower KD, the higher affinity Allow us to measure the fraction of receptors occupied to reach a full biological response

Question 26

What is a graded response curve?

Answer 26

Continuous data points needed

Question 27

What is a quantal response curve?

Answer 27

Response is discrete: yes/no; impossible to make a graded curve; eg with toxicity alive or dead

Question 28

What is ED50?

Answer 28

50% Effective Dose | The dose at which 50% of maximum effect is achieved.

Question 29

What is LD50?

Answer 29

50% Lethal Dose | the dose at which 50% of the animals die.

Question 30

What is TD50?

Answer 30

50% Toxic Dose | the dose at which 50% of the humans developed toxicity.

Question 31

What is the therapeutic index? How is it measured?

Answer 31

A measure of drug safety Therapeutic index = LD50 / ED50 (animal) Therapeutic index = TD50 / ED50 (human)

Question 32

What is tachyphylaxis?

Answer 32

Responsiveness drop rapidly after administration of a drug (i.e. tolerance) Diminished response with subsequent doses

Question 33

What affects tachyphylaxis in pts?

Answer 33

Age, gender, body size Dz state, genetics Co-administration with other drugs

Question 34

At a cellular level, why does tachyphylaxis occur?

Answer 34

Drug conc. change at receptors site Soluble receptor conc. Change Change in number or function of transmembrane receptors When agonist induces decrease # of receptors  down regulation of receptors or desensitization Change in components different from receptor (i.e. disease compensatory mechanism)

Question 35

What are the 2 types of desensitization?

Answer 35

Homologous desensitization | Heterologous desensitization

Question 36

What is homologous desensitization?

Answer 36

Decreased response at a single type of receptor (i.e. only the activated receptors are “turn off”) Loss of response to one single subtype of receptor agonist-dependent Rapid (seconds~minutes) receptor stays in the plasma membrane (usually) Ex: Continuous administration of Nitrates reduce in drug response  must allow nitrate free period

Question 37

What is heterologous desensitization?

Answer 37

Decreased response at two or more types of receptor (i.e. activation of one receptor resulted in the inhibition of another) = “Cross desensitization” – unresponsiveness to a variety of other agonists after prolonged stimulation by one agonist agonist-independent Slow (min~hrs) receptor is internalized (usually) Ex: Morphine inducing desensitization of opioid-receptors leading to desensitization to other opioid agonists

Question 38

What is drug inactivation?

Answer 38

The loss of ability of a receptor to respond to stimulation by a drug or ligand. Complete turning off the receptor may result from phosphorylation of the receptor  completely block the signaling activity  lead to the removal of the receptor from the cell surface.

Question 39

What is the refractory period/

Answer 39

The time lapse between the first and the next interaction of a drug that can produce an effect on a receptor Voltage-gated Sodium channel mediate firing of the neuronal action potentials are subject to refractory periods.