1. Pharmacodynamics 1 - Receptors

Front 1

3 main things encompassed by Pharmacodynamics:

Back 1

1. Mechanism of action of drugs
2. Therapeutic uses
3. Side effects

Front 2

What does Pharmacodynamics refer to in general?

Back 2

How a drug acts on the body

Front 3

What does Pharmacokinetics refer to in general?

Back 3

The mechanisms by which the BODY handles a drug.

Front 4

What are the 4 main constituents of Pharmacokinetics?

Back 4

-Absorption
-Distribution
-Metabolism
-Elimination

Front 5

What is the main theory of how most drugs interact with the body and cause an effect on it?

Back 5

Drugs interact with functional macromolecular components of the organism

Front 6

What DON'T drugs do to cause an effect on the body?

Back 6

Drugs do not CREATE effects, they MODIFY ongoing functions.

Front 7

What is one of the most common type of functional macromolecular components with which drugs interact?

Back 7

Receptors

Front 8

What two steps make up the Dual Function of drugs?

Back 8

1. Binding of drug to receptor
2. Transduction of binding into response

Front 9

Which step in the dual function is reversible? Which is irreversible?

Back 9

Binding = reversible
Transduction = irreversible

Front 10

What type of reaction do we call the reaction of Drugs with their Receptors?

Back 10

Bimolecular

Front 11

Who are the 3 researchers that first developed theoretical constructs for how drugs exert effects on physiologic responses?

Back 11

-Claude bernard
-Paul ehrlich
-JR Langley

Front 12

What did Claude Bernard study?

Back 12

The locus of action of CURARE at the frog neuromuscular junction.

Front 13

What is Curare?

Back 13

A paralytic poison that blocks ACh from binding the nicotinic receptor.

Front 14

What is Paul Ehlich given credit for? (3 things)

Back 14

1. Discovering receptors
2. Chemotherapeutic index
3. Specificity of drug interaction

Front 15

What is the chemotherapeutic index?

Back 15

The ratio of a drug's beneficial:toxic effects

Front 16

What did JR Langley study?

Back 16

The antagonism between curare and nicotine

Front 17

What term was coined by JR Langley?

Back 17

Receptive substance

Front 18

Do all drugs produce effects by interacting with receptors?

Back 18

No

Front 19

What are 3 other ways that drugs can produce effects other than by binding to receptors?

Back 19

-Inhibition of enzymes
-Inhibition of transporters
-Inhibition of ion channels

Front 20

What is an enzyme inhibitor? What does it inhibit?

Back 20

Captopril - inhibits ACE (angiotensin converting enzyme)

Front 21

What is a Transporter inhibitor? What transporter does it inhibit?

Back 21

Cocaine - inhibits Dopamine uptake carriers

Front 22

What is an Ion channel inhibitor? What channel does it inhibit and what is the effect?

Back 22

Glibenclamide - blocks the K/ATP channel; effect is increased insulin release from the pancreas

Front 23

How does Heparin work?

Back 23

By binding Thrombin and Antithrombin; not a receptor.

Front 24

Are the pharmacodynamics of drugs that act by alternative mechanisms than binding to receptors any different?

Back 24

No; the same principles govern them all.

Front 25

What are 3 ways in which Receptors are excellent drug targets?

Back 25

-Specificity
-Selectivity
-Sensitivity

Front 26

How do drugs that target Receptors provide SPECIFICITY?

Back 26

Only a subset of receptors will be bound by the drug

Front 27

How do drugs that target Receptors provide SELECTIVITY?

Back 27

When the drug binds its certain subset of receptors, only specific signaling pathways that are coupled to the receptors are activated

Front 28

How do drugs that target Receptors provide Sensitivity?

Back 28

When the drugs bind their receptors, the transduction events are always AMPLIFIED intracellularly.

Front 29

What are the 3 general Classification schemes of receptors?

Back 29

1. Pharmacological
2. Biochemical
3. Molecular/structural

Front 30

What is the Pharmacological classification of receptors based on?

Back 30

Structure activity studies that show the structural features of the LIGANDS

Front 31

Give example of how the Pharmacological classification of receptors works:

Back 31

Muscarinic receptors are bound by the ligand Muscarine;
Nicotinic receptors are bound by the ligand Nicotine

Front 32

What is the Biochemical classification of receptors based on?

Back 32

The transduction mechanism that occurs when ligand binds to a given receptor.

Front 33

How are nicotinic and muscarinic receptors named based on biochemical classification?

Back 33

Nicotinic = ligand gated ion channels
Muscarinic = Gprotein coupled receptors

Front 34

What is the Molecular classification of receptors based on?

Back 34

Families of Similar Gene Products

Front 35

What is the law that determines drug ligands binding to receptors?

Back 35

The law of mass action

Front 36

What is the Law of Mass Action?

Back 36

Effect is determined by the masses of reactants

Front 37

What is K1?
What are its units?

Back 37

The rate constant for association of L + R into LR
Units = (1/sec)(1/M^2)

Front 38

What is K2?
What are its units?

Back 38

The rate constant for dissociation of LR complex
Units = (1/sec)(1/M)

Front 39

What is happening to the rates of association and dissociation of L + R at equilibrium?

Back 39

The two reactions are occuring at the same rate

Front 40

What is K2/K1?

Back 40

The Equilibrium Dissociation Constant --> Kd

Front 41

When does K2/K1 = Kd?

Back 41

At equilibrium

Front 42

What else is K2/K1 equal to?

Back 42

[L][R]/ [LR]

Front 43

What does the Kd equilibrium dissociation constant describe?

Back 43

The goodness of fit between the ligand drug and its receptor

Front 44

What is Kd inversely related to?

Back 44

The affinity of the ligand for its receptor

Front 45

What are the units of Kd?

Back 45

Molar

Front 46

Which Beta adrenergic receptor mediates the antihypertensive effects of B-blockers?

Back 46

Beta-1

Front 47

Which Beta adrenergic receptor mediates bronchoconstriction?
For what patients is this important?

Back 47

-Beta-2
-Important for hypertensive asthmatics - you want to selectively bind B1, not B2

Front 48

If Propanolol has a Kd for the
B1 receptor = 2.4 nM
B2 receptor = 2.7 nM
Which receptor does Propanolol have a higher affinity for?

Back 48

B1 receptor - it has a lower Kd hence a higher affinity for it

Front 49

If Atenolol has a Kd for B1 that is 1400 nM and a Kd for B2 that is 6250 nM, how does Atenolol compare to Propanol in terms of affinity?

Back 49

Its Kd is way higher than Propanolol for both Beta receptors; hence its affinity is much much lower

Front 50

So the 2 equations for Kd are:

Back 50

1. Kd = K2/K1

2. Kd = [L][R]/[LR]

Front 51

What is [R]?

Back 51

The concentration of free receptors

Front 52

Do we really know what [R] is?

Back 52

No; so we define Rt

Front 53

What is Rt?

Back 53

An estimate of the total number of receptors in a cell or tissue including those that are both bound and unbound by drug.

Front 54

What is the resulting equation when you substitute Rt for R in the equation for Kd and rearrange it to solve for [LR]?

Back 54

[LR] = Rt[L]/Kd+[L]

Front 55

Substituting the total amount of receptor into the equation for Kd and rearranging allows us to determine:

Back 55

The concentration of Ligand-Receptor complexes

Front 56

What do we see if we plot the concentration of [LR] against increasing concentrations of [L]?

Back 56

A rectangular hyperbola

Front 57

What does the asymptote of the hyperbola from an [LR] vs [L] graph represent?

Back 57

The total amount of receptors - so the conc of [LR] is equal to Rt at very high conc of [L]

Front 58

What is the conc of [LR] when the concentration of [L] is equal to the dissociation constant?

Back 58

[LR] = 1/2(Rt)