NSAIDS

Question 1

Autacoids

Answer 1

Paracrine/autocrine hormones released in response to injury

Serotonin, histamine, kinins, lipid derivatives

Question 2

Eicosanoids

Answer 2

20Carbon chains with short 1/2 lives - means it will act locally

Question 3

Prostaglandin identification

Answer 3

Stimulated uterine contractions and lowered BP

Question 4

PG made from, what do they bind, half lives, and what they do

Answer 4

From AA
Bind surfac receptors 
Short T1/2 
Short duration of response need continuous synthesis
Local responses in tissues

Question 5

Phospholipase A2

Answer 5

Rate limiting enzyme in PG production…liberates AA from the membrane

Question 6

COX enzyme catalyzes formation of

Answer 6

Prostaglandins, prostacyclins, thromboxanes

Question 7

Phospholipase C

Answer 7

Liberates IP3

Question 8

COX reaction

Answer 8

Forms unstable intermediate from AA…then final product formed depending on the cell type

Question 9

AA linear pathway

Answer 9

Creates Leukotrienes…not target for NSAIDs

Question 10

What is NSAID disadvantage?

Answer 10

Bluntly inhibits synthesis of all prostaglandins…there are wide variety of effects

Question 11

Prostaglandins mediate action of

Answer 11

Inflammation
Smooth muscle
Thrombosis
Parturition
GI secretions 
Renal phys
Development

Question 12

Glucocorticoids

Answer 12

Adrenal steroids with anti-inflam effects

Question 13

Glucocorticoid systemic side effects

Answer 13

Immunosuppression

Question 14

Steroid hormones come from

Answer 14

Cholesterol

Question 15

Glucocorticoid action

Answer 15

Inhibits synthesis of COX at gene expression level
Upregulates Lipocortin Annexin 1 that inhibits phospholipase A2

Block RL step

This is longer lasting but longer onset to work

Question 16

NSAID effects

Answer 16

Antiinflam
Antipyretic (fever)
Analgesic (pain)
Platelet effects
Gastric
Renal
Cardiovascular
Gout

Question 17

NSAID action

Answer 17

Competitive inhibitors of COX 1 and 2

Quicker acting than glucocorticoids

Question 18

Aspirin is a

Answer 18

Salicylate

Question 19

Salicylate (aspirin) uses

Answer 19

Prophylactic for thromboembolic (clotting) dz (cardiac and cerebral)

Question 20

Pregancy and aspirin

Answer 20

Decrease birth weight and increase in mortality, anemia, and hemorrhage

Question 21

Aspirin uses

Answer 21

Analgesia
Antiinflam
Antipyretic
INhibit platelet aggregation
Prevent colorectal cancer

Question 22

Aspirin contraindiciation

Answer 22

Peptic ulcers
Pregnancy
Childrne with viral infections
Reye’s syndrome

Question 23

Aspirin mechanism

Answer 23

Irreversible inhibitor of COX…metabolite of salicylate is also an NSAID…acetal group covalently bound to serine hydroxyl group of COX

Question 24

Very low doses of aspirin

Answer 24

1mg/Kg…baby aspirin

Antiplatelet

Question 25

Low doses of aspirin

Answer 25

10mg/ky | Analgesic and antipyretic

Question 26

High doses of aspirin

Answer 26

100mg/kg Antiinflam Need high does because aspirin doesn't work as well in acidic environment of macrophages

Question 27

Side effects of aspirin

Answer 27

Tinnitus Deafness Vertigo

Question 28

NSAIDs and gastric functions

Answer 28

AA normally produces PGI2 and PGF2 that works on parietal and epithelial cells...it decreases the proton pump and therefore increase secretion of mucouse...if this is inhibited, mucous decreases and pH decreases so more likely to cause ulcer

Question 29

Acetominophen is a

Answer 29

Analgesic and antipyretic but NOT antiinflammatory

Question 30

When is acetominophen used as aspirin alt

Answer 30

Peptic ulcer Allergies Viral infection Hemophiliacs

Question 31

Contraindication of acetominophen

Answer 31

Post op

Question 32

Acetominophen main side effect

Answer 32

Fatal hepatic necrosis (liver death)...found in lots of other meds

Question 33

Acetominophen no effect on

Answer 33

Clotting and Gout

Question 34

Acetominophen liver toxicity with alcohol

Answer 34

Glutathione acetyltransferase typically neutralizes...in presence of alcohol CYP2E1 is increased and glutathione is lowered

Question 35

Tx of acetominophen OD

Answer 35

Activated charcoal to decrease abs in first 4 hours N acetyl cysteine (PO or IV) Supportive ABCD tx If this doesn't work, then liver transplant

Question 36

NAC

Answer 36

Precursor to glutathione

Question 37

COX 1 vs COX 2

Answer 37

COX 1 is constituitively active COX 2 is inducible COX1 - stomach, intestine, kidney, platelet COX2 - macros and synoviocytes

Question 38

Glucocorticoids on COX

Answer 38

Block both NSAIDS can be tailored

Question 39

Selectivity for 1 vs 2

Answer 39

Indomethacin and aspirin - COX 1 Naproxen and Ibuprofen - Both Meloxicam, diclofenac, and celecoxib - COX2 more than 1

Question 40

Celecoxib is different because

Answer 40

Better for people at high risk for heart dz...5X more cost thoguh

Question 41

Prostaglandins in development

Answer 41

PGE2 helps patent ductus arteriosis/foramen ovale...NSAIDs can avoid need for surgery

Question 42

COX 1 knockouts

Answer 42

No ulcers, no renal dysfunction, majority died

Question 43

COX 2 knockouts

Answer 43

No inflam disruption Females anovulatory Serious renal deficiencies

Question 44

NSAIDS and cancer

Answer 44

Tumors express high levels of COX 2...both aspirin and COX 2 inhibitors have reduced size and number of colorectal polyps in animal models

Question 45

Piroxicam

Answer 45

Suppressed growth of human cancer cells

Question 46

Sulindac

Answer 46

Decreased incidence in animal models

Question 47

Cardiovascular risk of NSAIDS

Answer 47

Can increase risk of cardiovascular events RIsk may increase with use Possibly increase risk of CV dz Contraindicated for coronary artery bypass grafts periop pain

Question 48

NSAID GI risk

Answer 48

Bleeding, etc. | May occur anytime, espcially in elderly patients

Question 49

NSAIDS with all 3 activities

Answer 49

Celecoxib, diclofenac, ibuprofen, indomethacin, meloxicam, naproxen

Question 50

NSAIDS with just analgesic and antipyretic

Answer 50

Acetominophen