Golan Pharm Chapter 2

Front 1

Pharmacodynamics

Back 1

The effect of drugs on the body, distinct from pharmacokinetics, which is the body's effect on a drug(metabolism)

Front 2

First-line treatment of MI in the absence of catheterization options (and possibly in their presence)

Back 2

Treatment with thrombolytics and anticoagulants.

Front 3

As drug concentration increases . . .

Back 3

. . . the concentration of bound receptors will increase.

Front 4

As free receptor concentration increases . . .

Back 4

. . . the concentration of bound receptors will increase.

Front 5

Does a drug's effect increase with a larger concentration of the drug, larger number of receptors, or both?

Back 5

Both.

Front 6

A lower drug dissociation constant . . .

Back 6

. . . indicates a tighter drug-receptor binding affinity, and therefore a greater number of bound receptors (larger potency) at all doses as opposed to a drug with a higher dissociation constant

Front 7

[DR]/[Rtotal]

Back 7

Fractional occupancy, or the fraction of all receptors that are currently bound to a drug.

Front 8

Two major types of dose-response relationships

Back 8

1. Graded - effect of various doses on a person
2. Quantal - effect of various doses on a population

Front 9

Potency versus efficacy

Back 9

Potency is the concentration of the drug at which it elicits 50% of it's maximal response. Efficacy is the maximal response. As you could imagine, a drug can be highly potent (low, low Kd or EC-50) but also have a low, low efficacy (think about it like Vmax). And vice versa.

Front 10

When a drug is at efficacy?

Back 10

Addition of more drug will have no response (like Vmax). But unlike Vmax, the receptors do not ALL have to be occupied for a drug to have achieved maximal response.

Front 11

Difference between drug-receptor binding curve and graded dose-response curve.

Back 11

Basically, right now, nothing except terminology. On a Drug-R curve, there is Kd and Ro, while on the Dose-R curve we call the same values EC-50 and Emax.

Front 12

Values to know on a quantal dose-response curve.

Back 12

ED50 - 50% of pop. show therapeutic response to drug
TD50 - 50% of pop. show toxic response to drug.
LD50 - 50% of pop. show lethal response to drug.

Front 13

Why is a quantal curve called that?

Back 13

Because it only measures yes or no endpoints (alive/dead, therapy/no therapy), discretely like quanta. A graded curve, by contrast, shows all valued effects of a response from min to max.

Front 14

What concept does agonist-receptor binding illustrate?

Back 14

We think of a drug binding to a receptor as formation of a DR complex, but it doesn't end there. An agonist creates a DR complex and stabilizes the receptor in an "active" configuration. The creation of the complex alone is potency, while the "active" configuration is a measure of efficacy.

Front 15

More potent drugs versus more efficacious drugs

Back 15

Potent drugs have a low Kd, or tighter binding (high affinity) for their receptor. Efficacious drugs, regardless of binding affinity, cause more receptors to be in an "active" configuration.

Front 16

Antagonist

Back 16

A molecule that inhibits receptor activity ONLY IN THE PRESENCE OF AN AGONIST. That agonist can be another drug or an endogenous ligand.

Front 17

Outline of Antagonist subtypes

Back 17

I. Receptor antagonists
a. Active site binding
i. Reversible = Competitive Antagonist
ii. Irreversible = non-competitive antagonist
b. Allosteric binding
i. Reversible/Irreversible - noncompetitive allosteric
II. Nonreceptor antagonists
a. Chemical
b. Physiologic

Front 18

Equation for antagonist behavior

Back 18

AR <--> A + D + R <--> DR. This shows that an Antagonist-Receptor complex cannot go directly to an active state.

Front 19

Mathematically, what does a competitive antagonist do to the Kd of a drug?

Back 19

It raises it, therefore lowering potency by a specific factor. If A is the competitive antagonist, and D is the agonist, or drug, then the Kd is raised by (1+ [A]/Ka)

Front 20

Does a competitive antagonist affect efficacy?

Back 20

No. It shifts the dose-response curve to the right, but does not lower its Emax.

Front 21

Pravastatin

Back 21

A statin. Competitive antagonist to HMG-CoA for the HMG CoA reductase enzyme, therefore lowering cholesterol synthesis.

Front 22

Noncompetitive antagonist

Back 22

Can bind to allosteric or active site. Binds with highest affinity or covalently, therefore cannot be overcome with increased agonist concentration. STOPS RECEPTOR ACTIVATION.

Front 23

Does a noncompetitive antagonist reduce potency or efficacy?

Back 23

Efficacy. It reduces the concentration of available receptors, thus permanently lowering a drug's maximal potential effect.

Front 24

Aspirin

Back 24

Noncompetitive antagonist. Irreversibly acetylates cyclo-oxygenase, stopping thromboxane synthesis. Effects can last as long as 10 days.

Front 25

Chemical antagonist

Back 25

Inactivates agonist by modifying or sequestering it.

Front 26

Protamine

Back 26

Chemical antagonist. Binds to heparin and inactivates the whole family of anticoagulants.

Front 27

Physiologic antagonist

Back 27

Activates or inactivates a receptor that acts in direct opposition to the agonist receptor.

Front 28

Partial agonist

Back 28

Exactly what it sounds like. Elicits a less than maximal effect even when all receptors are bound. Can act like a competitive antagonist, because it competes for the same site and elicits less of a response. Lowers Emax and raises EC50, or Kd.

Front 29

Problem with partial agonist theory?

Back 29

If a receptor only has an active or resting state, how does a partial agonist elicit a "lesser" response? Is there a "lesser" active state?

Front 30

Two hypotheses to explain how a partial agonist could work.

Back 30

1. The partial agonist is capable of stabilizing both the inactive AND active states.
2. A receptor may have several active conformations, some less ideal than others.