Pharmocology // Exam 1 [Lecture 2]

Front 1

_______: First major legislation. In the 30's there was an antibiotic that was formulated with a solvent- The solvent proved to be toxic and killed about 100 people. This regulation was the one that required safety and toxicity information/testing for our drugs.

Back 1

Food, Drug, and Cosmetic Act, 1938

Front 2

_______: Main legislation that required the other main component to testing- Effectiveness! Rigorous testing requirements for new drugs.

Back 2

Kefauver-Harris Amendments, 1962

Front 3

Which drug legislation came into effect due to the "thromidilyde disaster"- Pregnant women were using it as a sleep aid and there were teratogenic effects.

Back 3

Kefuaver-Harris, 1962

Front 4

________: Defines schedules I, II, III, IV, and V based on potential for abuse. Enforced by the DEA!!

Back 4

Controlled Substances Act, 1970

Front 5

_________: Increased availability of generic drugs.

Back 5

Hatch-Waxman Act, 1984

Front 6

_________: Placed restrictions on labeling of supplements.

Back 6

Dietary Supplement Health and Education Act, 1994

Front 7

T/F: Supplements are required to go through FDA drug review/approval process.

Back 7

FALSE; Supplements are NOT required to go through FDA drug review

Front 8

Which drug legislations are enforced by the DEA?

Back 8

Controlled Substances Act

Front 9

Which drug legislations are regulated by the FDA?

Back 9

Food, Drug, Cosmetic Act

Kefauver-Harris Amendments

Front 10

What is our biggest concern regarding supplements?

Back 10

The interactions with other drugs we give them.

Front 11

Schedule I drugs have the [highest/lowest] potential for abuse.

Back 11

HIGHEST

Front 12

What are examples of schedule II drugs?

Back 12

Morphine, pure opiod drugs, cocaine

Front 13

What is an example of a schedule IV drug?

Back 13

Valium

Front 14

What are schedule V drugs?

Back 14

Over-the-counter (ex: small amount of codeine in cough syrup)

Front 15

What are the three stages of a new drug development?

Back 15

Pre-Clinical

Clinical

Marketing

Front 16

__________: Stage before the drug goes into humans. Test tubes and animals; Define the drug's potential for toxicity.

Back 16

Pre-Clinical

Front 17

__________: How the drug will move around in the body.

Back 17

Pharmacokinetics

Front 18

Submit all data to FDA in IND, and if the FDA approves, what happens?

Back 18

The sponsor will then ready the drugs for human use in phase 1 clinical trial.

Front 19

________: Stage where drug is tested in humans.

Back 19

Clinical

Front 20

Describe the phase 1 clinical trial.

Back 20

-Focused on pharmacokinetics, safety, and dose

-Relatively small number of people (~20-80)

-Usually use healthy people

-Lasts about 1 year

*Some drugs we can't give to healthy people; for example, cancer drugs

Front 21

Describe the phase 2 clinical trial.

Back 21

-Focused on effects and safety

-Around 100-300 people

-Effectiveness: is this drug doing anything to the receptor to produce effect.

-About 2 years in length

Front 22

Describe the phase 3 clinical trial.

Back 22

-Involves a blinded controlled study

-Rigorous design

-Involves ~1000-3000 people

-About 3 years in length

-Main focus: Effectiveness and safety

Front 23

During which phase do most drugs fall out and don't continue in the drug development?

Back 23

Phase 3 clinical trial.

Front 24

If completion of phase 3 clinical trail, what happens?

Back 24

They will submit a new drug application to the FDA --> If the FDA thinks it supports effectiveness and safety, they will go on to MARKETING.

Front 25

T/F: Post marking surveillance has really increased.

Back 25

TRUE

Front 26

What does the "black box" refer to?

Back 26

If a drug gets a black box, it has a particularly notable adverse affect profiled that we need to be aware of.

Ex: Embryo-fetus death

Front 27

An example of a ________ name is N-acetyl-para-aminophenol.

Back 27

Chemical name

Front 28

Example of a ________ name is acetaminophen.

Back 28

Generic name

Front 29

Generic names are assigned by who?

Back 29

The US Adopted Names Council

Front 30

_________ names are proprietary, selected by pharmaceutical companies, and are created for marketing purposes.

Back 30

Brand or Trade Name!

Front 31

What is an example of a brand/trade name?

Back 31

Children's Non-Aspirin

Apap

Children's Feverall

Pain Reliever

Tylenol (for acetaminophen)

Front 32

T/F: We should focus on the generic name; generic name is the way to go with drugs.

Back 32

TRUE

Front 33

Name some factors that determine how a patient responds to drug.

Back 33

-The way we administer the drug

-How the drug moves in the body

-Pharmacodynamics (involves looking at the drugs and how they interact with receptors)

Front 34

What is pharmacodynamics?

Back 34

The actions of the drug on the body.

-Drug + receptor interactions

-Biological responses

Front 35

What is pharmacokinetics?

Back 35

The actions of the body on the drug.

Front 36

__________: Molecule that binds to receptor; Can be drug we give or molecule made in body.

Back 36

Ligand

Front 37

_________: Macromolecule to which the drug binds.

Back 37

Receptor

Front 38

Basically our drugs are either _______ or ________ those naturally occuring ligands.

Back 38

Mimicking OR blocking

Front 39

What are the 4 basic types of receptors?

Back 39

-G protein coupled receptor

-Enzyme linked receptor

-Ion channels

-Intracellular

Front 40

T/F: Receptors are proteins.

Back 40

True

Front 41

Which of the 4 receptors is used by more than HALF of the drugs we give?

Back 41

G protein coupled

Front 42

Where are receptors often located? How does the receptor allow the drug to move?

Back 42

Receptors (as proteins) are often sitting on the cell membrane. A drug that may not be able to move through the cell membrane can interact with the receptor on the outside of the cell membrane and that message move through to the inside of the cell and that's where biochemical reactions occur --> Biological effect.

Front 43

T/F: Generally speaking, receptors tend to localize on certain regions in the body.

Back 43

TRUE

Front 44

How is having localized receptors a good thing?

Back 44

If we can design a drug to act on a receptor that's only in one part of the body where the problem is being experienced then that will result in therapeutic effects and fewer adverse effects

*If we have receptors spread extensively through the body, then we are going to run into a problem with a lot of potential for other effects outside of targeted therapeutic effects.

Front 45

Where are beta 1 adrenergic receptors?

Back 45

The heart and kidneys

Front 46

How do beta 1 adrenergic receptors work/affect response?

Back 46

Beta cells are stimulated and release renin.

Drugs called beta blockers are used to effectively treat various caridovascular disorders by (1) effecting function of the heart to reduce contractility & heart rate, and (2) block renin release in kidney.

Front 47

Where are the thyroid hormone receptors located?

Back 47

Not localized- Located on almost all cells in the body!

Front 48

How will the lack of localization of the thyroid hormone receptors affect drug activity?

Back 48

When we use a drug that effects the thyroid receptors, we will expect much broader activity --> Potential for broad effects and serious toxicities.

Front 49

How is a drug used to relax a blood vessel?

Back 49

Drug interacts with receptor --> Biochemical reactions occur --> Decrease calcium in muscle cells which will relax blood vessel and dilate it.

Front 50

________: Receptor family involving a membrane embedded receptor and enzymatic activity. See ligand binding and activation the receptor resulting in changes.

Back 50

Cell membrane/Embedded enzyme

Front 51

_________: Receptor family where ligand (once attached to channel), will produce a conformational change usually opening the channel and ions will pass through.

Back 51

Ligand-gated Ion Channel

Front 52

_________: Receptor family where ligand binds outside of cell, it can't get through the cell, the message goes across the membrane by this receptor drug interaction.

Back 52

G-Protein Couple Receptor

Front 53

________: Receptor family where drug is able to move into the cell and does NOT need a receptor on membrane. It interacts by going into the nucleus and will increase of decrease transcription of certain genes.

Ex: Steroid hormones, sex hormones, cortisol, thyroid.

Back 53

Transcription factor

Front 54

What are the two types of drug interactions?

Back 54

Agonist

Antagonist

Front 55

When drugs bind to receptors, do you generally want a weak or strong bond?

Back 55

WEAK, so that reversibility is an option.

*Include hydrogen or vanderwhals force

Front 56

Drugs that bind irreversibly to receptors are ______ bonds.

Back 56

Covalent

Front 57

How long do covalent bonds stay?

Back 57

Until the receptor regenerates; when a new one forms.

Front 58

_________: The attraction that the drug has for the receptor; so if it is highly attracted to it, then we might not need as much of the drug.

Back 58

Affinity

Front 59

________: Ability to activate that receptor; what we will find is that our blocker drugs just sit on the receptor, don't really do anything to it.

Back 59

Intrinsic activity

Front 60

_______ drugs activate receptor and mimic our natural chemicals in our body.

Back 60

Agonist

Front 61

__________: Mirror images and cannot be super imposed; Differ in chemical activity.

Back 61

Steroisomers

Front 62

What are the most common types of 2nd messengers?

Back 62

Cyclic AMP and cyclic GMP

Front 63

What is considered the "1st messenger"?

Back 63

The initial connection between the drug and receptor. 2nd messengers are the response to that biological effect

Front 64

T/F: Different signal transduction pathways give us a lot of opportunity about where the drug will act.

Back 64

TRUE

Front 65

Continuous drug + receptor interaction may lead to _________.

Back 65

An altered response; Tolerance

Front 66

__________: Tolerance that develops over a short period of time; within seconds or minutes loses response to that drug.

Back 66

Tachyphylaxis

Front 67

____________: When a receptor is blocked, the receptor reacts by increasing the number of receptors.

Back 67

Upregulation

Front 68

___________: When a receptor is blocked, the receptor reacts by decreasing the number of receptors.

Back 68

Downregulation

Front 69

What is an example of downregulation?

Back 69

-Opiod drugs: Must give higher doses each time.

-Cancer patients that need drugs for pain control: We have to eventually give doses so high that they would kill someone who had not been exposed to those drugs.

Front 70

An agonist drug [activates/blocks] a receptor.

Back 70

Activates

Front 71

What are the characteristics of an agonist drug?

Back 71

-Affinity (characteristics to bind to receptor)

-Intrinsic activity (capability to activate receptor)

Front 72

An antagonist drug [activates/blocks] a receptor.

Back 72

Blocks receptor!

Front 73

Characteristics of an antagonist drug.

Back 73

-Affinity/attraction for receptor

-Cannot do anything by sit there and block molecule from activating the receptor.

-Going to produce effect, but effect is dependent on what the endogenous ligand would be doing b/c it will block that action.

-Can also be used to block another drug at the same receptor

Front 74

What is the common name of the antagonist drug?

Back 74

"Blocker"

Front 75

________: Reduced maximal effect; have some agonistic activity but cannot elicit the full effect that the agonist drug would; less effective drug.

Back 75

Partial agonist

Front 76

T/F: If you have enough agonist present with antagonist, the agonist in high concentrations can overcome the blockage of the antagonist.

Back 76

True; IFFFF it is a "competitive" or "reversible binding"

Front 77

If the antagonist drug is irreversible, what does that mean?

Back 77

It is stuck covalently to the receptor; even if agonist drug is present, it cannot overcome that!

Front 78

Are there drugs that don't work via a receptor?

Back 78

Not many but a few:

-Antacid

-Osmotic laxatives

-Chelating agents

-Resins

Front 79

What shape do you get when you plot dose on a log scale?

Back 79

S-Shaped Curve

Front 80

The ______ is the steepest part of the curve.

Back 80

Slope

Front 81

Which is safer, a steeper or flatter slope?

Back 81

The drug with the flatter slope is safer because you don't see a dramatic increase of response with an increase in dose.

Front 82

From the dose response curve, we can find _______ and ______.

Back 82

Efficacy and potency

Front 83

_________: Maximal response produced by a drug.

Back 83

Efficacy

Front 84

________: Dose of drug required for a given response; Easily seen when comparing two drugs at the 50% point- Look at dose required for that level of response.

Back 84

Potency

Front 85

If efficacy is equal, does potency matter?

Back 85

No, unless there is a notable difference in the number of pills the person has to take.

Front 86

_______: Drug effects for a population of patients; Percentage of patients that are responding at these various doses.

Back 86

Quantal Dose Response

Front 87

_________: Measure of safety between toxic level we find and the therapeutic measure.

Back 87

Therapeutic index

Front 88

If there is a narrow therapeutic index, what does that mean?

Back 88

The number is low and the lines are relatively close together --> Toxicity could occur!

Front 89

If someone is taking narrow therapeutic index (NTI) drugs, what is required?

Back 89

The prescription must be refilled with the same product from the same manufacturer- Cannot substitute for other brands.

Front 90

________: Sum of individual effect. For example, when you combine alcohol with CNS depressant, it heightens both.

Back 90

Additive

Front 91

_______: Two drugs, that because of the way they interact with their receptors and work, they get MORE than additive effects.

Back 91

Synergistic

Front 92

_______: One drug is fighting against the other.

Back 92

Antagonistic

Front 93

_______: One drug that doesn't do a whole lot on its own and you combine it with another drug, you get a dramatic increase in effects.

Back 93

Potentiation

Front 94

T/F: Almost all of our drugs will have toxicity associated with them.

Back 94

TRUE

Front 95

What is interchangeable with "toxicity".

Back 95

"Adverse effect"

Front 96

T/F: Side effect is the same at adverse effect.

Back 96

FALSE; Side effect is not necessarily adverse--> Could have a drug that produces a side effect that doesn't really matter (ex: dry mouth)

Front 97

_________: Effects that occur unrelated to the dose; Unpredictable

Back 97

Idiosyncratic

*Ex: Allergy to penicillin

Front 98

________: cause mutation

Back 98

Mutagenicity

Front 99

________: cause cancer

Back 99

Carinogenicity

Front 100

________: Drug is going to cause effects on developing fetus.

Back 100

Teratogenicity