532 - Med Chem Ii - Exam Ii - Nsaids

Front 1

What are the 4 main classes of eicosanoids?

Back 1

1) prostaglandins, 2) thromboxanes, 3) prostacyclins, & 4) leukotrienes

Front 2

What two eicosanoids are biosynthesized from PGH2?

Back 2

Thromboxanes & Prostacyclin

Front 3

Eicosanoid structure

Back 3

derived from w-3 or w-6 C20 unsaturated fatty acids

Front 4

Eicosanoid properties

Back 4

found in every component of the body; involved in all signs of inflammation, redness, swelling, pain and heat

Front 5

Prostaglandin structure

Back 5

15-alpha -OH and a trans double bond at C13; naturally occurring 20C cyclopentano-fatty acid derivatives

Front 6

Thromboxanes

Back 6

facilitate platelet aggregation and are vasoconstrictors

Front 7

Prostacyclin

Back 7

primarily prevents platelet aggregation and is a vasodilator

Front 8

Leukotrienes

Back 8

biosynthesized from arachidonic acid by lipoxygenase and are involved in inflammation and asthma

Front 9

cyclooxygenase reaction

Back 9

arachidonic acid to PGG2

Front 10

Arachidonic acid

Back 10

a w-6 C20 unsaturated fatty acid

Front 11

NSAIDs mechanism of action

Back 11

inhibit PG (prostaglandin) biosynthesis at the cyclooxygenase step

Front 12

Aspirin properties (3)

Back 12

antipyretic, analgesic, and anti-inflammatory properties

Front 13

By what mechanism does aspirin modify COX?

Back 13

Covalently- the only NSAID that does this

Front 14

Does aspirin modify or inhibit COX1?

Back 14

inhibit (irreversibly)

Front 15

Does aspirin modify or inhibit COX2?

Back 15

modify

Front 16

Does aspirin irreversibly or reversibly inhibit COX1?

Back 16

irreversibly

Front 17

Is aspirin more potent at COX1 or COX2?

Back 17

COX1

Front 18

What two things is aspirin synthesized from?

Back 18

1) salicylic acid & 2) acetic anhydride

Front 19

Side effects of aspirin?

Back 19

GI effects (bleeding and ulceration) - related to COX1 inhibition

Front 20

Where is the -OH in salicylic acid derivatives? 

Back 20

In the ortho position. NOT meta or para because that would abolish its activity.

Front 21

SAR of salicylic acid derivatives (3)

Back 21

1) conversion of carboxylate group to amide maintains analgesic activity but NOT anti-inflammatory action, 2) removing -OH or placing in meta or para position abolishes activity, & 3) substitution of aromatic rings at the 5 position enhances anti-inflammatory activity

Front 22

What is the major metabolite of salicylic acid?

Back 22

Salicyluric acid (75%)

Front 23

What is salicyluric acid composed of? 

Back 23

salicylic acid and glycine (via amide bond)

Front 24

What are the arylalkanoic acids?

Back 24

nonselective COX inhibitors that mimic arachidonic acid

Front 25

Similarities between arylalkanoic acids and arachidonic acid? (5)

Back 25

1) acidic group mimics the -CO2H. any other acid group sub decreases activity, 2) the acidic group is located 1 C away from a flat ring (mimics the 5- and 8- double bonds), 3) the second lipophilic group mimics the 11- double bond and enhance the activity, 4) the 5 position of the indole ring are substituted in most cases, & 5) the presence of an indole nitrogen is NOT essential for activity

Front 26

Is the N in the indole ring of indomethacin necessary for activity?

Back 26

NO

Front 27

What class of drug is indomethacin?

Back 27

arylalkanoic acid

Front 28

Is indomethacin more or less potent (analgesic or antipyretic) than aspirin?

Back 28

MORE

Front 29

What is the main structural features of the aryl- or heteroarylpropionic acids?

Back 29

an aromatic ring, 1 carbon, a methyl and a carboxylic acid of that 1 carbon.

Front 30

How to enhance the activity and reduce side effects of the aryl- and heteroarylpropionic acids?

Back 30

Add an alpha methyl group on the alkanoic acid portion

Front 31

What class does ibuprofen belong to?

Back 31

arylpropionic acid

Front 32

Which form of ibuprofen is active?

Back 32

S(+) isomer but the the R(-) enantiomer was inverted to the S(+) in vivo

Front 33

Is ibuprofen more or less potent than aspirin?

Back 33

MORE

Front 34

Is ibuprofen more or less potent than indomethacin?

Back 34

LESS

Front 35

Are the metabolites of ibuprofen active or inactive?

Back 35

INACTIVE

Front 36

Which COX form has a larger binding pocket?

Back 36

COX-2

Front 37

Which COX contains Ile?

Back 37

COX-1

Front 38

Which COX is specific to inflamed tissue?

Back 38

COX-2

Front 39

Which COX is associated with less gastric irritation?

Back 39

COX-2

Front 40

Which COX contains Val?

Back 40

COX-2

Front 41

Is acetaminophen anti-inflammatory?

Back 41

NOPE. but it can treat inflammatory "pain"

Front 42

What is acetaminophen a metabolite of?

Back 42

acetanilide and phenacetin (also antipyretic analgesics)

Front 43

What side effect are the COX-2 selective inhibitors associated with?

Back 43

Cardiovascular problems (Vioxx)

Front 44

How is the reactive metabolite of acetaminophen normally detoxified?

Back 44

Hepatic glutathione (GSH)

Front 45

What are the two hepatotoxic metabolites of acetaminophen?

Back 45

N-hydroxyamideand N-acetylimidoquinone

Front 46

What happens in an APAP OD or with alcohol?

Back 46

the glutathione stores are depleted the quinone reacts with -SH groups on cysteine on hepatic proteins

Front 47

What AA reacts with the quinone in APAP OD or with alcohol?

Back 47

Cys in hepatic proteins