Basic Principles of Pharm part 2

Question 1

Agonist Mimics

Answer 1

Has the same effect as the agonist on the receptor, but works somewhere else (see explanation/picture in lecture 2 at 0:04:15)

Question 2

Irreversible antagonist

Answer 2

Covalently bind to receptor and do not come off. The only way to get rid of it is to get rid of that receptor. Can be allosteric or orthosteric.

Question 3

Partial agonist

Answer 3

Will bind to the active site and elicit a partial response. They compete for the same active site as a full agonist. (see lecture 2 @ 0:12:27)

Question 4

How can a partial agonist act as an antagonist?

Answer 4

The full and partial agonists compete for the same site. If the partial agonist takes up the receptor sites, it is not allowing the full agonist to bind therefore, you don’t have the max response you could have.

Question 5

Partial agonist by itself VERSUS partial agonist in presence of full agonist

Answer 5

Partial is an agonist by itself.

Partial is an antagonist in the presence of a full agonist.

Question 6

Opposite charge antagonist example

Answer 6

Heparin (-) binds to Protamine (+) rendering heparin ineffective (has nothing to do with binding to receptors, has everything to do with drug-to-drug interaction in bloodstream)

Question 7

Physiologic antagonism

Answer 7

Drugs acting at different receptors that counter act each other (ex: Epi binding to Beta and acetylcholine binding to muscarinic)

Question 8

Receptor configuration: unbound

Answer 8

Ri (inactive) Ra (active)

can switch on and off spontaneously

Question 9

Receptor configuration: bound with agonist

Answer 9

Ri –>Ra

favors active state

Question 10

Inverse agonist (and example)

Answer 10

Ri

Question 11

Sympathetic nervous system (SNS)

Answer 11

Fight or flight

Question 12

Parasympathetic nervous system (PSNS)

Answer 12

Rest and digest

Question 13

Factors that determine the duration of a drugs effects:

Answer 13

• As long as the drug stays bound to receptor.
• If a drug initiates the production of a protein, it will take longer to see effects and longer for response to stop.
• Receptor is degraded (in covalent bonding)
• Desensitization

Question 14

Good receptor properties:

Answer 14

• Selective

- Alteration

Question 15

Bad receptor properties:

Answer 15

• “Inert binding sites” (non-selective)

- Drug carriers (don’t elicit a response)

Question 16

Potency

Answer 16

A drug is potent when it requires a very low dose to elicit 50% of that drugs maximal effect (Or its EC50).

Question 17

If a drugs EC50 is low..

Answer 17

..the drug is very potent.

Question 18

Efficacy

Answer 18

The maximal response you will see from a particular drug (see lecture 2 at 0:33:05)

Question 19

ED50

Answer 19

Median effective dose

Question 20

TD50

Answer 20

Median toxic dose

Question 21

LD50

Answer 21

Median lethal dose

Question 22

EC50 vs ED50

Answer 22

EC50: The concentration of drug in blood.
ED50: The actually dose being given.

Question 23

Therapeutic index

Answer 23

Establishes the margin of safety of a drug.

TD50/ED50

Question 24

The higher the Therapeutic Index..

Answer 24

..the safer the drug.

Question 25

Idiosyncratic

Answer 25

means we don't know why one patient responds differently to a drug than another patient

Question 26

Tolerance

Answer 26

Response changes over the course of time

Question 27

Tachyphylaxis

Answer 27

Quick tolerance

Question 28

Causes of variation:

Answer 28

- Alteration in concentration of drug that actually reaches the receptor (rate of absorption/distribution/clearance, age, weight, sex, disease state) - Concentration of endogenous ligand (maybe affected by health or disease - Alteration in function and number of receptors - Changes in components of response distal to receptor (largest and most important cause)

Question 29

Toxic effects

Answer 29

Some drugs produce both desired and adverse effects at the same receptor. other drugs bind to different classes or receptors

Question 30

Pharmacokinetics: ADME:

Answer 30

Absorption Distribution Metabolism Elimination

Question 31

4 main ways a drug will permeate through the body:

Answer 31

``` Aqueous diffusion Lipid diffusion Special carriers Endocytosis and exocytosis (*all of these depend if drug is charged/uncharged and size) ```

Question 32

Aqueous diffusion

Answer 32

Larger aqueous compartments in body (ex: blood) Cells may have aqueous channels Diffusion by concentration gradient Molecules can be large

Question 33

Not aqueous diffusion

Answer 33

Highly charged molecules | Bound to large proteins (carriers)

Question 34

Lipid diffusion

Answer 34

Easiest to cross barriers | example: gases

Question 35

Special carriers

Answer 35

Protein that will bind to a drug and move it from one area to another. Use active transport (energy required) or facilitated diffusion

Question 36

In Fick's law of diffusion, flux is...

Answer 36

..how fast a drug will move from one side of a barrier to another

Question 37

Flux is largely dependent on..

Answer 37

..concentration gradient.

Question 38

If the concentration of one side of a barrier is significantly more than on the other side, what will happen to the flux? (Fick's law)

Answer 38

The flux will be very large

Question 39

If the surface area of a barrier is very large, what will happen to the flux? (Fick's law)

Answer 39

The flux will be very large

Question 40

If a barrier is very thick, what will happen to the flux? (Fick's law)

Answer 40

The flux will be very small

Question 41

Endocytosis Exocytosis

Answer 41

Membrane engulfment of molecule Can be receptor mediated Slow process Very large or charged molecules Merging of vesicle with membrane

Question 42

Henderson Hasselbach Equation

Answer 42

pH= pKa + log [A-]/[HA]

Question 43

If pH = pKa..

Answer 43

..the ratio of ionized versus unionized is equal

Question 44

If pH < pKa..

Answer 44

..favors protonated form

Question 45

If pH > pKa..

Answer 45

..favors un-protonated form

Question 46

What part of the kidneys are most drugs filtered at?

Answer 46

Glomerulus

Question 47

Concentration of drug in renal tubules is dependent on what?

Answer 47

pH

Question 48

"Trapping" drugs in urine: | Weak acids excreted faster in..

Answer 48

Alkaline urine

Question 49

"Trapping" drugs in urine: | Weak bases excreted faster in..

Answer 49

Acidic urine