Introduction

Question 1

Pharmacodynamics

Answer 1

What the drug does to the body

Question 2

Pharmacokinetics

Answer 2

What the body does to the drug

Question 3

What types of toxic studies are done?

Answer 3

1. Acute
2. Subacute
3. Chronic
4. Reproductive
5. Carcinogenics
6. Mutagenic

Question 4

Acute studies

Answer 4

2 species, 2 routes

Determine minimal lethal dose

Question 5

Subacute studies

Answer 5

2 species, 3 doses

Note biochemical and physiological effects

Question 6

Chronic

Answer 6

Note biochemical and physiological effects

Question 7

With both subacute and chronic studies, what do we want to know

Answer 7

What doses

If anything causes toxicity

Question 8

Reproduction

Answer 8

Find out if fertility is affected by the drug

Question 9

Carcinogenicity

Answer 9

Note gross and histologic pathology

Question 10

Phase 1 clinical testing

Answer 10

Primary purpose: to determine pharmacokinetics - how is it metabolized

• new side effects?
• NON BLIND

Question 11

Phase 2 clinical testing

Answer 11

Determining effectiveness

• cross over
• single blind

Question 12

Phase 3 clinical testing

Answer 12

• double blind

- cross over

Question 13

Phase 4 clinical testing

Answer 13

Postmarketing surveillance

-report unexpected side effects

Question 14

Pure Food and Drug Act

Answer 14

Insures purity and proper labeling

Question 15

Federal Food, Drug, and Cosmetic Act

Answer 15

Requires toxicity studies to determine safety

Question 16

Kefauver-Harris Amendment

Answer 16

Mandated teratology testing

Requires proof of efficacy

Question 17

FDA Modernization Act

Answer 17

Expedited review for drugs for serious diseases

Question 18

What components make a drug lipophilic?

Answer 18

ring systems
aliphatic groups (e.g. -CH3)
carbon chains

Question 19

What components make a drug lipophobic?

Answer 19

amines
aldehydes
alcohols
carboxylic acids
phenols

Question 20

What is P-glycoprotein? Why is it important?

Answer 20

P-glycoprotein is a transporter. It can carry drugs across lipid membranes (uses ATP).

Question 21

What are some examples of P-glycoprotein importance?

Answer 21

1. pumps certain drugs/toxins actively back into GI lumen
2. proximal kidney tubules can pump drugs into lumen
3. pump some drugs into bile
4. transports some drugs/toxins out of brain, placenta
5. protects hematopoietic stem cells from toxins
6. protects organs of reproduction (ovaries, testes)

Question 22

What does a low Vd mean?

Answer 22

the molecule is lipid soluble - so it will penetrate to all tissues of the body and will be low in the plasma

Question 23

Why do levels of enzymes vary in different patients?

Answer 23

polymorphisms

Question 24

What is the main route of drug excretion?

Answer 24

the kidney

Question 25

The urine is usually …
most drugs are …

How are drugs excreted?

Answer 25

Urine - acidic
Drugs - basic

Bases like acid and are more easily excreted than acids. Bases get ionized so that they are not reabsorbed across lipid tubules

Question 26

Salicylate toxicity and urine

Answer 26

Urine in this condition will be basic, so give a drug to acidify urine and the drug will be excreted