Drug Metabolism

Question 1

Drug metabolism/Biotransformation is the (physical or chemical?) modification of drugs in the body which transforms relatively lipo___ agents into products more ____, hydro_____ products which can easily be excreted.

Answer 1

Chemical

philic; polar

philic

Question 2

Drug metabolism can Sometimes lead to chemical activation of inactive drugs to their active substrates

T/F
With examples

Answer 2

T
Enalapril to enalaprilat, Codeine to morphine

Question 3

Inactive to active

Enalapril to _______, Codeine to _____

Answer 3

enalaprilat

morphine

Question 4

Drug metabolism occurs Mainly in the _____, involves both ________ and ________ enzymes.

Answer 4

liver

microsomal and non microsomal

Question 5

Drug metabolism Occur in almost all organs of the body

T/F

Answer 5

T

Question 6

other relatively common sites for drug metabolism besides liver include the ____,_____,_____, and _____

Answer 6

lungs, kidney, GIT and the skin

Question 7

Drug metabolism is categorized MAINLY into 2 main reactions - ______ and ______ metabolism.

Answer 7

Phase I and Phase II

Question 8

Phase 1 of drug metabolism must occur before phase 2 of drug metabolism

T/F

Answer 8

F

Could occur in any order.

Question 9

Phase 3 reaction has also been described – Mainly involved in the removal of drugs that _________________ by _______ (_________)

Answer 9

have undergone phase 1 and or 2 reactions

transporters

P-glycoprotein

Question 10

Phase I Reactions/__________ reaction / ________ reaction

Answer 10

functionalization

nonsynthetic

Question 11

Phase 1 reaction

Convert parent compound into a more __________ metabolite by adding or unmasking ________ (-OH, -SH, -NH2, -COOH, etc.) eg._____

Answer 11

polar (=hydrophilic)

functional groups

oxidation

Question 12

Phase 1 reactions include _____,________, and _________ reactions. Others ________,______

Answer 12

Oxidative, reductive and hydrolytic

cyclization and decyclization

Question 13

Main function of phase I reactions is to prepare chemicals for ________ and _____

Answer 13

phase II metabolism and subsequent excretion.

Question 14

The drug May be sufficiently polar after phase 1 to be excreted readily
T/F

Answer 14

T

Question 15

phase 2 metabolism involves,

________ with ________ to further increase aqueous solubility

Include ____,_____,_______,______,_____etc

Answer 15

Conjugation

endogenous substrate

glucoronide, sulfate, acetate, amino acid, glycine

Question 16

Phase ____ is the true “detoxification” step in the metabolism process

Answer 16

II

Question 17

Microsomal enzymes

Located on ____ in the ____,_____,_____,_____

Answer 17

sER

liver, kidney, lungs , intestinal mucosa

Question 18

Example of microsomal enzymes include

____,________,______,_______

Answer 18

Monooxygynases, cytochrome P450, UGT, epoxide hydroxylases

Question 19

Microsomal enzymes are only involved in phase 2 reactions

T/F

Answer 19

F

Involved in phase 1 and 2 reactions

Question 20

Non-microsomal enzymes

Can be found in _______,______,______

examples include ____,______

Answer 20

Cytoplasm, mitochondria, plasma

Esterases, amidases,

Question 21

Microsomal cytochrome P450

Act on only structurally related drugs
T/F

Answer 21

F

They act on structurally unrelated drugs

Question 22

Microsomal cytochrome P450
which _____ drugs

Answer 22

oxidize

Question 23

Microsomal cytochrome P450 ,__________ family of enzymes

Answer 23

monooxygenase

Question 24

_______ enzyme Metabolizes the widest range of drugs.

Answer 24

Microsomal cytochrome P450

Question 25

_______ enzyme metabolizes the widest range of drugs

Answer 25

Microsomal cytochrome P450

Question 26

Cytochrome P450 system These enzymes are _____-bound, _______-containing protein.  

Answer 26

membrane; heme

Question 27

The human CYP family consists of ___ genes, with ___ families and _____ subfamilies.

Answer 27

57 18 44

Question 28

Examples of human CYP enzymes include _____,____,____,_____,_______

Answer 28

CYP2D6, CYP2C19, CYP2C9, CYP3A4 and CYP3A5.

Question 29

The enzymes are named based on the _____ - Eg CYP3A4 belongs to ______ — , ______ —, and ________ —-

Answer 29

family family 3 subfamily A gene number 4.

Question 30

CYP ______ is involved in a significantly higher number of drug metabolism compared to the other enzymes.

Answer 30

CYP3A4

Question 31

Inhibition of CYP enzymes - ___eased degradation of co-medicated drugs, ____eased drug plasma concentrations, Risk of ___________. Inhibitors: _______,______, MAO Inhibitor (_________)

Answer 31

Decr Incre severe adverse events cimetidine Isoniazid Phenelzine

Question 32

Induction of CYP enzymes - ___eased degradation of co-medicated drugs , ____eased drug plasma concentrations , Loss of ________ , Risk of _________. Inducers: _______,________,______, cyclophosphamide

Answer 32

Incr Decr pharmacological effect therapeutic failure barbiturates; rifampicin, carbamazepine

Question 33

Who is a more efficient metabolized between human and rats?

Answer 33

Rats

Question 34

Diseases affecting the liver will (reduce or increase ?) rate of drug metabolism.

Answer 34

reduce

Question 35

Testosterone is an enzyme (inducer or inhibitor?)

Answer 35

inducer

Question 36

felodipine inhibited by _____

Answer 36

grape juice

Question 37

Progesterone in an enzyme (inducer or inhibitor ?) .

Answer 37

inducer

Question 38

Placenta contains metabolizing enzymes T/F

Answer 38

T

Question 39

Drugs with extensive first pass effect include – _______,______,______,______

Answer 39

lidocaine, propranolol, nitroglycerin, morphine

Question 40

Puritane (hinders or enhances?) sleep

Answer 40

Enhances

Question 41

List all the inhibitors of cyp450

Answer 41

Cimetidine Isoniazid Grapejuice fruit Phenelzine Omeprazole Ketoconazole Erythromycin Refonavir

Question 42

List the inducers of cyp450

Answer 42

Carbamazepine Rifampicin Barbiturates Cyclophosphamide St John’s wort

Question 43

Diazapam (hinders or enhances?) sleep

Answer 43

Enhances

Question 44

Diazepam taken with ______ would make you sleep longer Why?

Answer 44

Cimetidine Cimetidine inhibits cyp450 that would metabolize diazepam

Question 45

Why don’t you give insulin orally?

Answer 45

Because of the first pass effect

Question 46

First pass effect is _____ proportional to bioavailability

Answer 46

Inversely

Question 47

L-dopa is given orally T/F With reason

Answer 47

F Sue to the presence of dopa decarboxylase

Question 48

Propranolol has (high or low?) bioavailability

Answer 48

Low

Question 49

Determining bioavailability is important for calculating ________ for nonintravenous routes of administration.

Answer 49

drug dosages

Question 50

Bioavailability is the rate and extent to which an ___________. For example, if 100 mg of a drug is administered orally and 70 mg is absorbed unchanged, the bioavailability is _____ or ____%%

Answer 50

administered drug reaches the systemic circulation 0.7 or 70

Question 51

Bioavailability of a drug given orally is the ratio of the __________ to the __________________

Answer 51

AUC following oral administration AUC following IV administration

Question 52

First-pass hepatic metabolism: When a drug is absorbed from the _______, it enters the ______ before entering the ______. If the drug is rapidly metabolized in the _______ or ______ during this initial passage, the amount of unchanged drug entering the systemic circulation is ____eased.

Answer 52

GI tract; portal circulation; systemic circulation liver or gut wall Decr

Question 53

First-pass metabolism by the ______ or ______ limits the _______ of many oral medications.

Answer 53

intestine or liver efficacy

Question 54

For example, more than __% of nitroglycerin is cleared during first-pass metabolism. Hence, it is primarily administered via the _______ or _______ route.

Answer 54

90 sublingual or transdermal

Question 55

Drugs with high first-pass metabolism should be given in doses sufficient to ensure that enough active drug reaches the desired site of action. T/F

Answer 55

T

Question 56

Very hydrophilic drugs are (poorly or well?) absorbed Why? drugs that are extremely lipophilic are (poorly or well?) absorbed Why?

Answer 56

Poorly because of their inability to cross lipid-rich cell membranes. Poorly because they are totally insoluble in aqueous body fluids and, therefore, cannot gain access to the surface of cells.

Question 57

For a drug to be readily absorbed, it must be largely _____, yet have some solubility in ______ This is one reason why many drugs are either _______ or ______

Answer 57

lipophilic aqueous solutions. weak acids or weak bases.

Question 58

penicillin G, are stable in the pH of the gastric contents. T/F

Answer 58

F unstable

Question 59

insulin, are destroyed in the ______ by degradative enzymes.

Answer 59

GI tract

Question 60

Two drug formulations are bioequivalent if they show comparable _____ and similar times to __________

Answer 60

bioavailability achieve peak blood concentrations.

Question 61

UGT-_____________

Answer 61

Uridine diphosphate-glucuronyltransferase (UGT)

Question 62

UGT converts the (toxic or non-toxic?) form of ____ ( ___________ ) to its (toxic or nontoxic?) form (________), making it able to be dissolved and removed from the body.

Answer 62

Toxic ; bilirubin unconjugated bilirubin Non toxic; conjugated bilirubin

Question 63

List 4 microsomal enzymes

Answer 63

Monooxygynases, cytochrome P450, UGT, epoxide hydroxylases

Question 64

List 2 Non microsomal enzymes

Answer 64

Esterases, amidases,

Question 65

Progesterone in an enzyme ( inducer or inhibitors?)

Answer 65

Inducer

Question 66

Drugs with extensive first pass effect include – ________,________,______,______

Answer 66

lidocaine, propranolol, nitroglycerin, morphine