lecture 3

Question 1

a drug is terminated by its ____

Answer 1

metabolism

Question 2

____ are inactive when given, activated in the body

Answer 2

prodrugs

Question 3

sites of drug metabolism

Answer 3

• skin
• lungs
• kidney
• *liver

Question 4

rapid metabolism in the liver

Answer 4

first pass metabolism

Question 5

drugs that highly metabolized in liver

Answer 5

nitroglycerine and morphine

Question 6

liver cell enzymes or enzyme complexes are called

Answer 6

cytochrome P450 (CYP)

Question 7

what liver cells contain cytochrome P450?

Answer 7

smooth endoplasmic reticulum cells

Question 8

most significant CYP?

Answer 8

CYP 3A4

Question 9

what type of reactions do CYP catalyze?

Answer 9

oxidation

Question 10

CYPs can be reduced or inhibited by ____

Answer 10

environmental factors

Question 11

CYP inhibitors

Answer 11

grape fruit juice, some antibacterials, antifungals antihistamines

Question 12

CYP activators

Answer 12

phenytoin, phenobarbital, st. john’s, rifampin

Question 13

CYP inhibitors ____ dose in body, CYP activators ____ dose in body

Answer 13

increase, decrease

Question 14

Phase 1 reactions work to:

Answer 14

make small changes to make drug polar, get inside kidney tubule

Question 15

Phase 1 CYP450 reactions

Answer 15

• hydroxylation
• N-oxidation
• S-oxidation
• N-dealkylation
• O-dealkylation

Question 16

Phase 1 non CYP450 reactions

Answer 16

• deamination (remove amine group, maybe to ketone)
• hydrolysis (esterase - ester into alcohol and water)
• peptidase (cleaves peptide bonds)
• phsphatase (removes phosphate)

Question 17

Phase 2 reactions work to:

Answer 17

• add a moiety to the drug, a large molecule

Question 18

Phase 2 reactions:

Answer 18

• acetylation
• glucuronidation
• methylation
• sulfation
• glycination

Question 19

phase 1 is ____, phase 2 is _____

Answer 19

inactivation, detoxification of the drug

Question 20

drug excretion mechanism

Answer 20

• feces, urine, lung, sweat, breast milk

Question 21

factors that can alter absorption

Answer 21

• age; older you get the less you metabolize

- environment; other drugs can affect absorption

Question 22

factors that can alter distribution

Answer 22

• fat

- gender

Question 23

factors that can alter metabolism

Answer 23

• genetic factors (CYP450 difference, slow acetylation)
• age
• disease, pregnancy, exposure of drugs

Question 24

slow acetylators

Answer 24

• procainamide and hydralazine

Question 25

how many stages of testing a new drug

Answer 25

• 4

Question 26

first part of testing

Answer 26

• animal testing

Question 27

phase 1

Answer 27

• dose dependent effect in normal human volunteers

Question 28

phase 2

Answer 28

• in small # of patients with target disease

Question 29

phase 3

Answer 29

• in larger # of patients

Question 30

phase 4

Answer 30

• apply for new drug application (NDA)