Drug Dev/Laws

Question 1

Preclinical Trials

Answer 1

DISCOVERY
okay’ed on animals- ID potential RISKS and TOXICITY in 2 diff species
ID max dose and lethal dose

Question 2

Clinical Trials - Phase 1

Answer 2

SAFETY

done in healthy volunteers

Question 3

Clinical Trials - Phase 2

Answer 3

EVALUATE EFFICACY and ACTIVE DOSES
done in 100 pts with disease/condition
short-term S/E and tox

Question 4

Clinical Trials - Phase 3

Answer 4

CONFRIM EFFICACY and SAFETY
1000 pts with disease
usually inc toxicities are seen

Question 5

Phase 4

Answer 5

Goal: ESTABLISH Safety & Tolerability

Question 6

Pharmacokinetic Principles

Answer 6

What influences absorption rates?

1. • or - charge
2. lipophilic
3. site of absorption
4. Formulation
5. Bioavailability

Question 7

Oral administration

Answer 7

Absorption: variable

convenient

Question 8

IM

Answer 8

Absorption: Rate depends on drug formulation and blood flow

Painful

Question 9

IV

Answer 9

Absorption: Immediate effect

Good for emergencies and large volumes of meds

Question 10

Inhalation

Answer 10

Absorption: Rapid lung absorption

Gets to site of action with minimal systemic effects, need good technique

Question 11

Transdermal

Answer 11

Absorption: Formulation dependent

Convenient, prolonged release with constant levels

Question 12

Topical

Answer 12

Absorption: Poor systemic absorption
good for derma, opthalmic, nasal, otic meds
Dosing not as precise

Question 13

What population is volume of distribution important?

Answer 13

Obese, pts with a lot of fluid, or known to have a high vol dist need to have a higher drug conc

Question 14

Define prodrug?

Answer 14

Must be broken down by the liver to be converted to active metabolites *First pass effect
Take into accnt pts liver

Question 15

First pass effect

Answer 15

Orally admin drugs metabolized significantly resulting in significant reduction in dose reaching the circulation

Question 16

Phase 1 rxn

Answer 16

• creates a lipid soluble cmpd -> water soluble cmpd

ex: oxidation via cytochrome P450

Question 17

Significance of Cytochrome P450

Answer 17

Pathway drug MUST take to be broken down.

• Induction: increase metabolism/excretion of drug -> dec therapeutic effect
  ex: Rifampin
• Inhibition: decrease metabolism/excretion of drug -> inc effect
  ex: Erythromyocin + Sumvastin

Question 18

-AZOLE P450

Answer 18

1A2, 3A4 Inhibitor

Question 19

AMIDARONE P450

Answer 19

3A4 Substrate

Question 20

RIFAMPIN P450

Answer 20

1A2, 3A4, 2C9, Inducer

Question 21

PHENYTOIN P450

Answer 21

2C9 Substrate

3A4, 2C9 Inducer

Question 22

FLUOXETINE P450

Answer 22

2C9 Substrate

Question 23

Phase II RXN

Answer 23

produce a metabolite with improve water solubility

• elimination of drug from tissue
  ex: glucronidation, sulfation
• –Acetaminophen metabolism uses both

Question 24

Steady-state conc

Answer 24

time to steady state is independent of conc

it is attained after ~ 4 half lives

Question 25

Loading dose

Answer 25

May require more drug initially to reach maintenance (ex. seizure meds), and then can drop to maintenance

Question 26

Pharmacodyamics

Answer 26

study of physiological effects of drugs and their MOA

Question 27

Regulatory Proteins

Answer 27

mediate actions of chemical signal

ex: NT, hormones

Question 28

Enzymes

Answer 28

Dihydrofolate reductase - receptor for methotrexate

Question 29

Transport proteins

Answer 29

Na+/K+ ATPase - receptor for digoxin

Question 30

Structural proteins

Answer 30

Tubulin - receptor for colchicine