Exam 1 Ch 1 Intro Pharm--Nature, Drug Development

Question 1

What is Pharmacology?

Answer 1

Study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes

Question 2

What is Medical Pharmacology?

Answer 2

Science of substances used to prevent, diagnose, and treat disease

Question 3

What is Toxicology?

Answer 3

Branch of pharmacology that deals with the undesirable effects of chemicals on living systems

Question 4

What is Pharmacokinetics?

Answer 4

• What the BODY does to the DRUG
• Great practical importance in the choice and administration of a particular drug for a particular patient e.g. renal function

Question 5

What is Pharmacodynamics?

Answer 5

• What the DRUG does to the BODY

- Determines the group in which the drug is classified e.g. beta blockers

Question 6

Define the meaning of Drug.

Where can a drug be synthesized?

Answer 6

• Any substance that brings about a change in biologic function through its chemical actions.
• Can be synthesized within the body (i.e. hormones) or can be chemicals not synthesized in the body (i.e. Xenobiotics)

Question 7

What type of drug has almost exclusively harmful effects?

Answer 7

Poisons

Question 8

What is a Receptor?

Answer 8

Target molecule in the biologic system that plays a regulatory role

Question 9

What is an Agonist?

Answer 9

A compound that binds to a receptor and produces the biologic response by activating the receptor

Question 10

What is an Antagonist?

Answer 10

A compound that binds to a receptor, but does NOT activate generation of a signal, BLOCKS receptor

Question 11

What does an antagonist chemically?

Answer 11

It interferes with the agonist ability to activate the receptor.

Question 12

Which does not have an effect on its own: an agonist or antagonist?

Answer 12

Antagonist

Question 13

What are the 6 factors that play a role in successful drug-receptor interactions?

Answer 13

S-T-A-R-E-S

S- Size
T- Transportation from site of administration to site of action
A- Atomic Composition
R- Reasonable rate of elimination (appropriate duration of action)
E- Electrical Charge
S- Shape

Question 14

What are Toxins? Where do toxins come from?

Answer 14

• Poisons of biologic origins

- Synthesized from plants or animals

Question 15

Whether a drug is solid (i.e. aspirin), liquid (i.e.nicotine), or gaseous (i.e. nitrous oxide) at room temperature will determine the best what?

Answer 15

These factors will determine the best route of administration.

Question 16

What are some examples of inorganic elements that can be useful or dangerous in their physical nature when using them as a drug?

Answer 16

Lithium
Iron
Heavy Metals

Question 17

What are some examples of organic drugs? The physical nature of organic drugs have important implications for the way they are handled in the body. Why?

Answer 17

Some examples are weak acids or bases.

pH differences in different parts of the body may alter the degree of ionization of weak acids or bases

Question 18

Drug size varies between 100-1000 molecular weights. What is the lower limit set for?

Answer 18

The lower limit is set by the requirements for specificity of action.

Question 19

Drug size varies between 100-1000 molecular weights. What is the upper limit set for?

Answer 19

The upper limit in molecular weight is determined primarily by the requirement that drugs must be able to move within the body (i.e. from the administration site to action site)

Question 20

What occurs when the drug is larger (molecular weight greater than 1000)?

Answer 20

The drug does not diffuse readily between body compartments.

Question 21

In what scenario could very large drugs (MW greater than 1000) be administered to a patient?

Answer 21

Administrated directly into compartment where they have their effect
EX: Alteplase

Question 22

What are the 3 types of drug-receptor bonds?

Answer 22

1. Covalent
2. Electrostatic
3. Hydrophobic

Question 23

What are Covalent Drug-receptor Bonds?

Answer 23

Very strong bonds

In many cases not reversible under biologic conditions, have to wait a while for this bond to be degraded

Question 24

What are Electrostatic Drug-receptor Bonds?

Answer 24

• More common and weaker bonds than covalent bonds
• Vary from relatively strong linkages between permanently charged ionic molecules
• To weaker hydrogen bonds
• And to very weak induced dipole interactions such as van der Waals forces
• *MOST COMMON because of the weaker bonds**

Question 25

What are Hydrophobic Drug-receptor Bonds? What important interaction are these types of drug-receptor bonds involved with?

Answer 25

• Usually quite weak bonds
• Important in the interactions of highly lipid-soluble drugs with the lipids of cell membranes
• *NOT necessarily the weakest, in between ionic and covalent bonds**

Question 26

Why are drugs that bind to their receptors through weak bonds generally more selective than binding by means of very strong bonds?

Answer 26

Weak bonds require selectivity or a very precise fit of the drug to its receptor if an interaction occurs

Question 27

What are the steps in discovering a new drug?

Answer 27

I-D-S-M

1. Identify new drug target
2. Design based on mechanism and structure
3. Screening for activity and previous drugs
4. Modifications chemically

Question 28

Drug is to key as….

Answer 28

Receptor is to lock

Question 29

In the case of a drug’s enantiomer, do they fit to the receptor the same?

Answer 29

No, usually one stereoisomer is more potent than its mirror image and can fit better in the receptor

Question 30

If one receptor is more active than another, is it more active than all?

Answer 30

No, just because more active than one type of receptor, does NOT means it’s more active than another receptor type (ex: carvedilol)

Question 31

Are drug-metabolizing enzymes usually stereoselective?

Answer 31

Yes, but enantiomers may have different durations of actin

Question 32

What are racemic mixtures?

Answer 32

Both “R” and “S” enantiomers

Question 33

What are the steps for screening a drug?

Answer 33

P-T-A-A-S-C

P- Pharmacological Profile
T- Toxic effects (expected and unexpected)
A- Animal Models
A- Activity Screening
S- Study effects
C- Comparisons

Must meet each criteria to move on the the next step

Question 34

Drug metabolizing enzymes are usually stereoselective, and stereoselectivity varies between receptors. How does carvedilol demonstrate this?

Answer 34

Carvedilol is an alpha and beta blocker. The S enantiomer is 100x more potent at the beta receptor than then R enantiomer. However, the R and S enantiomers are equipotent at the alpha receptor.

Question 35

What are three major confounding factors in clinical trials?

Answer 35

1. Variable natural history of most diseases
2. Presence of other diseases and risk factors
3. Subject and observer bias and other factors

Question 36

Describe crossover design

Answer 36

Study participants are randomly assigned to different treatments during period 1. Then, during the washout period, they go back to their normal medication or none at all depending if they were on a medication for their condition prior to the study. During period 2, the treatments are switched.

Question 37

What is the placebo response and how is it quantitated?

Answer 37

Patients respond in a positive way to any therapeutic intervention by interested, caring, and enthusiastic medical personnel. It may involve objective physiologic and biochemical changes as well as subjective changes associated with the disease. It is quantitated by administration of an inert material with exactly the same physical appearance, odor, consistency as the active dosage form.

Question 38

List and describe the phases involved in drug approval, and approximately how long they last on a timeline.

Answer 38

1. In vitro studies (years 0-2): involving biologic products, chemical synthesis and optimization, culminating in choosing a lead compound.
2. animal testing (years 2-4) to determine efficacy, selectivity, and mechanism. IND application submitted at the end.
   Years 4-8:
   Phase 1: 20-100 subjects, “is it safe, pharmacokinetics?”
   Phase 2: 100-200 patients, “does it work in patients?”
   Phase 3: 1000-6000 patients, “does it work, double blind?”
   *Drug metabolism and safety assessment begins during animal testing and proceeds throughout clinical testing.
   Years 8-9: New Drug Application
   If approved, Phase 4: postmarketing surveillance, continuous
   Twenty years after filling NDA, patent expires.

Question 39

What is compliance and how is it confirmed in clinical trials?

Answer 39

Whether patients truly follow protocol; some patients in trials claim they are taking the drug as prescribed but are found on blood analysis to have not taken the drugs. Protocols for compliance are needed.

Question 40

What are adverse drug reactions, and how must they be handled before and after FDA approval of a new drug?

Answer 40

Harmful or unintended response. Before FDA approval, ALL adverse events must be reported. After FDA approval, surveillance, evaluation, and reporting must continue for any adverse event related to the use of the drug. Serious and unexpected events must be reported within 15 days.

Question 41

Describe orphan drugs and state what legislation sought to incentivize their development.

Answer 41

Orphan drugs are drugs for rare diseases, which are difficult to research, develop, and market. Development was incentivized by the Orphan Drug Amendment of 1983