Exam 1 - Metabolism and Excretion

Question 1

redistribution

Answer 1

drug moves away from its site of action; reducing its active concentration at the target site

Question 2

biotransformation (metabolism)

Answer 2

drugs are chemically alterd, usually in the liver, to inactive metabolites that are easier to excrete

Question 3

What are the two major effects of biotransformation?

Answer 3

1. usually converts substances to more hydrophilic compounds that are more readily excreted
2. usually converts substances to compounds that are less pharmacologically active

Question 4

What is Phase I of biotransformation?

Answer 4

introduction of small polar groups on the drug
* reaction classes: oxidations and hydrolysis
* product is usually more polar (hydrophilic)

Question 5

Phase I oxidations

Answer 5

• mixed functions oxidases
• monoamide oxidases

Question 6

explain the reaction of mixed function oxidases

Answer 6

drug + oxygen molecule –> drug-OH + water
* cytochrome P450s or CYPs
* metabolize wide variety of xenobiotics and endogenous compounds

Question 7

explain CYPs

Answer 7

• 3 families: CYP1, CYP2, CYP3
• each family has subfamilies

Question 8

explain the reaction of monoamine oxidases

Answer 8

monoamine (NH2) drug + oxygen molecule –> drug metabolite
* mainly impacts drugs affecting neurotransmission

Question 9

Phase I hydrolysis

Answer 9

cholinesterases (add a water)
* acetylcholinesterase
* plasma cholinesterase

• differ in molecules they prefer to metabolize
• differ in location in the body

Question 10

What is Phase II of biotransformation?

Answer 10

adding a larger polar molecule (glucuronic acid, sulfate) to a hydroxyl (-OH) group on the drug
* reaction classes: transferases
* products usually very polar

Question 11

Phase II enzymes

Answer 11

• glucuronyl transferases (UGTs)
• sulfotransferases (STs)
• catechol-O-methyltransferase (COMT)

Question 12

glucuronyl transferases (UGTs) reaction

Answer 12

drug-OH + activated glucose –> drug-glucuronide

Question 13

sulfotransferases (STs) reactions

Answer 13

drug-OH + activated sulfate –> drug-sulfate

Question 14

catechol-O-methyltransferase (COMT) reactions

Answer 14

mainly impacts monoamine drugs affecting neurotransmission

Question 15

active metabolite

Answer 15

drug metabolite that has significant activity (sometimes greater than parent compound)

Question 16

prodrug

Answer 16

inactive or relatively inactive precursor that is converted to a more active compound

Question 17

reactive metabolite

Answer 17

very toxic compound produced by biotransformation of a relatively inert substance (often reacts with protein or DNA)

Question 18

Where are common sites of biotransformation?

Answer 18

liver, GI tract, lungs, skin, kidneys, plasma

Question 19

Inhibitors of drug metabolism

Answer 19

• imidazoles
• macrolide antibiotics
• bioflavonoids (grapefruit)

Question 20

What are important points about drug metabolism inhibitors?

Answer 20

• decreased metabolism leads to increased drug levels
• each inhibtors affects different CYPs
• common site of drug-drug interaction

Question 21

factors influencing drug metabolism

Answer 21

• genetic (pharmacogenetics)
• disease states

Question 22

pharmacogenetics

Answer 22

the study of how an individual’s genetic makeup influences their response to drugs

Question 23

excretion

Answer 23

the drug and its metabolites are removed from the body; primarily through the kidneys or the liver

Question 24

What will a deficiency in an excretion route result in?

Answer 24

increased plasma concentration with subsequemt enhanced drug effects, unless the drequency or dose of a drug administered is reduced

Question 25

What is the site of filtration in the kidneys?

Answer 25

the glomerulus * drugs move from blood into kidney (renal) tubules along with rest of blood contents

Question 26

processes involved in drug excretion

Answer 26

* filtration (aqueous diffusion) * passive diffusion * carrier transport (transporters)

Question 27

What are the limitations of the kidneys?

Answer 27

* drug size * protein bound drug

Question 28

Where does filtration occur in the kidneys?

Answer 28

the glomerulus

Question 29

Where does carrier transport happen in the kidneys?

Answer 29

mainly in the proximal tubule

Question 30

Where does passive diffusion occur in the kidneys?

Answer 30

at any point along the tubule