lect 11 Non-steroidal anti-inflammatory drugs

Question 1

most common NSAIDS

Answer 1

aspirin

Question 2

two categories of NSAIDS

Answer 2

salicylates (aspirin) and non salicylates (ex ibuprofen, acetaminophen)

Question 3

History: compound extracted from plants and its derivative

Answer 3

salicylic acid and acetylsalicylic acid

Question 4

what does aspirin inhibit

Answer 4

synthesis of prostaglandins

Question 5

what cleaves section of plasma membrane fatty acids and what is being released

Answer 5

Phospholipase A2 and release of arachidonic acid

Question 6

structure of arachidonic acid and what it does

Answer 6

20 carbon, polyunsaturated fatty acid and acted on by enzymes to produce biologically active compounds

Question 7

enzymes that produce prostaglandins and thromboxanes

Answer 7

cyclooxygenases

Question 8

what two cyclo. produce prostaglandins

Answer 8

COX-1 AND COX-2

Question 9

change in structure from arachidonic acid to prostaglandins

Answer 9

formation of a ring and adding two carbons

Question 10

structure, place, role of cyclooxygenases

Answer 10

dimers so 2 equal active site, in the ER, converts arachidonic acid to prostaglandins

Question 11

true or false? prostaglandins have autocrine and paracrine functions

Answer 11

True

Question 12

inactivation of prostaglandins is fast or slow?

Answer 12

rapid fast inactivation

Question 13

other functions of prostaglandins

Answer 13

protect stomach from hydrochloric acid and thromboxanes involved in platelet aggregation and blood clotting

Question 14

true or false? Blocking prostaglandins can prevent intravascular coagulation and heart attacks

Answer 14

True

Question 15

prostaglandins have effects on what? (7)

Answer 15

Renal homeostasis, sleep cycle, reproductive system, vasodilation and vasoconstriction, platelet aggregation, blood flow to organs, pain and inflammation

Question 16

COX 1 activity and use

Answer 16

constitutively active and essential for physiological purposes like stomach protection platelet aggregation

Question 17

COX-2 activity and use

Answer 17

inducible, essential for pathological purposes like pain and inflammation

Question 18

prostaglandins act on what receptors

Answer 18

many different prostanoid receptor that have different subunits

Question 19

NSAIDS block prostaglandins that are implicated in what three things

Answer 19

fever (antipyretic), pain (analgesic), inflammation (anti anflammatory)

Question 20

Pain stimulus pathway

Answer 20

painful sensation going to spinal cord, relying in the thalamus, then the cortex, and then instantaneous reflex to withdraw from pain stimulus

Question 21

periphery in sensation of pain (2)

Answer 21

thermoreceptors, nociception

Question 22

injured cells release what

Answer 22

Mediators, including prostaglandins

Question 23

release on mediators have effect of what

Answer 23

nerve endings so impulses sent to spinal cord and up the brain

Question 24

involved in signaling from a variety of noxious stimuli (mediators released form injured cells and platelets)

Answer 24

nociceptive nerve endings

Question 25

NSAIDS act predominantly where

Answer 25

out in the periphery at the origin of pain stimuli and inflammation (nociceptors

Question 26

How does Nsaids work on periphery in relation to prostaglandins

Answer 26

blocks synthesis of PGs to decrease their intensity of the painful signal coming from periphery

Question 27

First stage usage when pain

Answer 27

NSAIDS

Question 28

Second stage usage when pain

Answer 28

OPIOiD and NSAIDS

Question 29

third stage usage when pain

Answer 29

OPIOIDS

Question 30

therapeutic usage of NSAIDS (5)

Answer 30

mild moderate pain like headache, inflammatory disorders, reduce fevers, prophylaxis of myocardial infarction and stroke, reduce risks of certain cancers

Question 31

chemical mediators inflammation pathway

Answer 31

released from injured tissue to local capillary bed which induces vasodilation and fluid and cells are drawn into injured area

Question 32

inflammatory mediators contribute to sensation of which nociceptors

Answer 32

sensitizing PGE2 or activating BK

Question 33

acute inflammation

Answer 33

cuts, allergic reactions

Question 34

chronic

Answer 34

cancer, arthritis, CV and neurological diseases

Question 35

what is osteoarthritis

Answer 35

injury induced joint damage

Question 36

what is Rheumatic arthritis

Answer 36

joints inflammed independent on the environment

Question 37

racehorses NSAID

Answer 37

equioxx

Question 38

arthritis common in excessive inbreeding

Answer 38

canine arthritis

Question 39

ASA or acetominophen should never be given to what animal

Answer 39

cat

Question 40

fever is induced by what

Answer 40

endogenous pyrogens that raise thermostatic set point in hypothalamus

Question 41

which PG major player for increasing setpoint in hypothalamus for fever

Answer 41

PG E2

Question 42

body response to pyrogens

Answer 42

temperature regulatying cenetr sends out impulses via ANS leading to increased heat production and decreased heat loss

Question 43

side effects of nsaids to upper GI tract

Answer 43

dyspepsia, erosions, ulcers, GI bleeding

Question 44

side effects of nsaids to renal

Answer 44

renal dysfunction, renal failure, blood pressure, heart failure

Question 45

why can NSAIDS cause blood loss

Answer 45

because of its anti platelet effect

Question 46

what lines the membrane layer of stomach and is protected by prostaglandins

Answer 46

gastric mucosa

Question 47

generic name for acetylsalicylic acid

Answer 47

aspirin

Question 48

how does aspirin inactivate COX (antithrombotic)

Answer 48

acetyl group of acetylsalicylic acid binds to serine residue in COX

Question 49

what is thromboxane A2

Answer 49

made in platelets which causes vasoconstriction and thrombosis (blood clots)

Question 50

does aspirin block thromboxane A2

Answer 50

yes

Question 51

true or false? Asprin can lower risks of colon cancer

Answer 51

true

Question 52

asprin half life and also at higher doses

Answer 52

3 hrs and 15 hrs

Question 53

aspirin (acetylsalicylic acid) is metabolized to what

Answer 53

salicylic acid

Question 54

enzymes that break down aspririn in lover

Answer 54

P450

Question 55

pharmacokinetics of NSAids in liver

Answer 55

P450 enzymes producing metabolites and glucoronyl transferases conjugating the metabolites to make water soluble glucuronide to be excreted by kidney

Question 56

pharmacokinetics of NSAids in liver

Answer 56

salicylic acid is an acid so reabsorbed by kidneys if tubules are acidic. for overdose, alkalinize urine so that weak acid wont be in unionized lipid soluble form and not be reabsorbed

Question 57

what do we call aspirin toxicity

Answer 57

salicylism

Question 58

sense of ringing in the ear

Answer 58

tinnitus

Question 59

neurological syndrom when children take aspirin

Answer 59

Reye's syndrome

Question 60

what can we give children instead of aspirin

Answer 60

acetaminophen

Question 61

aspirin binds reversibly or irreversibly

Answer 61

irreversiblly

Question 62

ibuprofen binds reversibly or irreversibly

Answer 62

reversibly

Question 63

types of ibuprofen

Answer 63

motrin, advil

Question 64

ibuprofen blocks what

Answer 64

both COX 1 AND 2

Question 65

cox 2 have constituitive effects on what

Answer 65

blood flow and kidney

Question 66

cox 2 is important for what

Answer 66

platelet inhibition and vasodilation

Question 67

which cox enxyme has a larger channel for arachidonic acid

Answer 67

cox 2

Question 68

highly selective and large cox 2 inhibitor drug

Answer 68

celecoxib

Question 69

why does cardiovascular problems occur with cox 2 selective inhibitors

Answer 69

the balance is shifted towards a prothrombotic state cause does not block cox 1

Question 70

who is prothrombotic

Answer 70

cox 1 because they make thromboxane

Question 71

who is antithrombotic

Answer 71

cox 2 because make prostacyclin

Question 72

asprin balance on cox enzymes

Answer 72

does not affect balance because acts on both cox 1 and cox 2. low doses bllocks cox 1 more and that for people with thrombosis

Question 73

which cox 2 inhibitor was withdrawn

Answer 73

rofecoxib

Question 74

cox 1 is highly concentrated where in the body and cox 2 where

Answer 74

gi tract and found in many places like brain, kidney...

Question 75

tradename drug most used (acetaminophen)

Answer 75

tylenol

Question 76

what is the main difference between acetaminophen and other nsaids

Answer 76

it is not anti inflammatory

Question 77

half life of acetaminophen

Answer 77

2-3 hours

Question 78

emzymes that break it down to a toxic metabolite

Answer 78

CYP450

Question 79

break down in liver of acetaminophen

Answer 79

breakon down to a toxic intermediate that is quickly conjugated

Question 80

what congugates acetaminphen

Answer 80

glutathione

Question 81

what is cellular necrosis

Answer 81

reaction with hepatocytes to kill liver cells if toxic intermediate of acetaminphen is not quickly conjugated

Question 82

overdose of acetaminophen?

Answer 82

enzymes that conjugate saturated so more toxic compound

Question 83

who are vulnerable to the toxicity of acetaminophen and why

Answer 83

alcoholics because chronic use of ethanol induces P450 enzymes that make the toxic metabolites

Question 84

effects at 0-24 hour stage of acetaminophen poisining

Answer 84

anorexia, nausea, vomiting

Question 85

effects at 24-72 hour stage of acetaminophen poisining

Answer 85

abdominal pain, elevated serum enzymes

Question 86

effects at 72-96 hour stage of acetaminophen poisining

Answer 86

synptoms of liver and renal failure and pancreatitis

Question 87

antidote of acetaminophenoverdose

Answer 87

glutathione precursor (N acetylcysteine) so that congugation can happen