Receptors

Question 1

____ ____ ____ is still the central dogma
of receptor activation

Answer 1

Lock and Key

Question 2

The 4 superfamilies of receptors:

Answer 2

1. Ligand-gated channels
2. G protein coupled receptors (GPCRs)
3. Enzyme/cytokine receptors
4. Ligand-activated transcription factors

Question 3

KNOW

What are:

• located on cell surface
• act by opening pores in the plasma membrane to allow ions to enter
• usually composed of multiple subunits
• usually multiple binding sites

Answer 3

Ligand-gated ion channels

Question 4

In skeletal muscle, target of succinylcholine is a nicotinic acetylcholine receptor is an example of what type of receptor?

Answer 4

ligand-gated ion channel

Question 5

This receptor is located on cell surface.

• Incredibly diverse array of activators; largest mammalian gene family
• Targets for high percentage of prescription drugs
• Signal transduction involves small _____ ______
• Probably operate as monomers, with some exceptions

Answer 5

G protein coupled receptors

second messengers

Question 6

These molecules can bind to G protein receptors: (7)

Answer 6

autocoids

light

tastants

odorants

neurotransmitters

hormones

Question 7

B-adrenergic receptor in heart is an example of:

Answer 7

G protein coupled receptor

Question 8

Located on cell surface, activated by growth factors or cytokines

i. single polypeptide with intrinsic enzymatic activity
ii. usually tyrosine kinases or guanylate cyclase
iii. sometimes receptor lacks enzyme activity but has
docking sites for another enzymes
iv. often dimerizes on activation to cross-phosphorylate and initiate intracellular signal

Answer 8

Enzyme/cytokine receptors

Question 9

What can bind to enzyme/cytokine receptors? (2)

Answer 9

Growth Factors
Cytokines

Question 10

What are enzyme growth factor inhibitors? (2)

Answer 10

Monoclonal antibodies

Small molecule tyrosine kinase inhibitors

Question 11

What receptor is located in cell nucleus, usually activated by steroids or other hydrophobic molecules

i. fairly common drug targets
ii. dimerize on binding agonist
ii. Agonist occupied dimers bind to DNA and alter gene
transcription

Answer 11

nuclear receptors

Question 12

These receptors blocks chain of activity to follow:

Answer 12

nuclear receptors

Question 13

What inhibitors are important in the treatment of cancer?

Answer 13

EGFR inhibitors

Question 14

Progestin receptor is an example of:

Intracellular protein, binds estrogen, dimerizes, translocates to nucleus and alters transcription of particular genes

Answer 14

nuclear receptor

Question 15

Sub-classification receptor types: (2)

Note: Within each super-family, receptors are classified based on the endogenous compound that binds to and activates them.

Answer 15

Adrenergic receptors: epinephrine and norepinephrine

Cholinergic receptors: acetylcholine

Question 16

______ receptors were historically divided into alpha and beta subtypes, but pharmacologic and genome advancements show alpha-1, alpha-2, and beta receptors each have three. For a total of 9 adrenergic receptor subtypes!

What receptor is “fast”? “Slow”?

Answer 16

Adrenergic

alpha

beta

Question 17

One would expect a ____ agonist to maximize the response curve.

Answer 17

full

Question 18

One would expect a ____ agonist to somewhat increase the response curve.

Answer 18

partial

Question 19

Binding of a drug to its receptor is usually a _______equilibrium

Answer 19

reversible

Question 20

The amount of drug receptor complex formed is related to drug ______.

Answer 20

concentration or dose

Question 21

Agonists have structural features that trigger a conformational change in receptor resulting in 2nd equilibrium leading ultimately to a cellular response. True or false?

Answer 21

true

Question 22

At equilibrium, rate of association = rate of dissociation is known as:

Answer 22

Mass Action Law

Question 23

What is the equilibrium dissociate constant?

Answer 23

K_d

Question 24

How do you solve for affinity? Give formula.

Answer 24

K_d

k_-1/k₁

[D] * [R] / [DR]

Question 25

Know units for: k₁ k_-1 k_d

Answer 25

M_-1*min_-1 min_-1 M

Question 26

The K_D value is expressed in concentration units and is unique for a drug/receptor pair. It is a numerical value describing the sum of chemical bonding forces between the two. True or false?

Answer 26

true

Question 27

Fractional occupancy equation (2 forms)

Answer 27

[DR] / [R_total] [D] / ( [D] + K_d)

Question 28

High Kd tells us ___ affinity.

Answer 28

low and vice-versa

Question 29

Kd tells us: * the affinity between a drug and receptor * reflective of the chemical bonding forces * a unique chemical fingerprint for a drug-receptor pair * approximate concentration of drug that occupies 50% of receptors in a preparation * allows you to predict receptor occupancy for any drug concentration without knowing anything more about the receptor Which is false and why?

Answer 29

tells us exact concentration of drug that occupies 50% of receptors

Question 30

The concentratrion of drug that occupies 50% of receptors in a preparation is\_\_\_.

Answer 30

Kd

Question 31

They fully activate only a fraction of the receptors they occupy.

Answer 31

partial agonists

Question 32

When spare receptors are present the preparation is much more sensitive to agonists, and the EC50 for an agonist may be much _____ than its Kd would predict.

Answer 32

lower (more potent)

Question 33

Often a maximal response can be achieved at less than full occupancy; other times, full occupancy is necessary for a full maximal response. This is known as the ____ \_\_\_\_\_ \_\_\_\_.

Answer 33

spare receptor concept

Question 34

EC50 is equal to Kd. True or false?

Answer 34

false

Question 35

EC50 is not equal to Kd because (4)

Answer 35

spare receptors the receptor activation equilibrium (for agonists) competition with endogenous activators impaired drug access to receptor

Question 36

Factors affecting drug distribution: Cellular reservoirs (3)

Answer 36

* Fat * lipid-soluble drugs * Bones/teeth * metals form insoluble phosphates * Increased Vd, biological half-life

Question 37

The rapidity of anesthesia into the brain depends on 2 factors:

Answer 37

* Blood flow * Crosses bbb easily

Question 38

Propofol has termination due to distribution out of brain and blood. True or false?

Answer 38

true

Question 39

Three phases of propofol PK ## Footnote ``` Redistribution phase (~\_\_\_ min) Rapid metabolic clearance (~\_\_\_ min) Slow phase (\_\_\_\_-\_\_\_hr) elimination from poorly perfused tissues ```

Answer 39

3 45 3-4

Question 40

Amount of drug excreted = glomerular filtration + \_\_\_\_\_\_ \_\_\_\_\_\_ - ______ \_\_\_\_\_\_

Answer 40

tubular secretion tubular reabsorption

Question 41

\_\_\_\_ ______ (units of **ml/min**) is volume of plasma from which drug is fully removed per unit time.

Answer 41

Renal clearance

Question 42

GFR depends on (3)

Answer 42

plasma protein binding volume of distribution blood pressure and blood flow

Question 43

Only _____ drug (both non-ionized and ionized) is filtered.

Answer 43

free

Question 44

Tubular reabsorption of sodium, water, creates a _______ gradient of drug in the urine, which is also concentrated, in the ____ tubule.

Answer 44

concentration proximal

Question 45

Drug reabsorption occurs via _______ diffusion, primarily in ____ \_\_\_\_\_ and ____ \_\_\_\_

Answer 45

passive distal tubule collecting duct

Question 46

Lipid soluble, ____ polar drugs (unmetabolized) are reabsorbed

Answer 46

less

Question 47

\_\_\_\_\_\_ drug is ______ in urine

Answer 47

Ionized excreted

Question 48

Therapeutic modulation of pH of the renal filtrate in drug overdose toxicity acidic drugs: enhanced excretion in ______ urine (NaHCO3)

Answer 48

alkaline