Nsaids Analgesic-Antipyretic And Anti-Infammatory Drugs Block 4

Front 1

General mechanism of NSAIDS
(Non-steroidal anti-inflammatory drugs)

Back 1

--inhibition of PG biosynthesis

--inhibits PG synthetase (cyclooxygenase) - COX-1 and COX-2.

-COX-1 is in all normal cells for homeostasis. COX-2 is induced by inflammation.

Front 2

Major differences between NSAID analgesics and narcotic analgesics

Back 2

(1) NSAIDs have much lower maximal effects than do opiods
(2) no addiction associated w/ NSAIDs
(3) free of unwanted CNS effects of the opiods
(4) treat low - moderate intensity pain

Front 3

Therapeutic Uses of NSAIDS

Back 3

Analgesic: only effective for low to moderate pain (especially pain due to inflammation). Not effective against sharp stabbing pain.

Antipyretics: Block IL-1 response in CNS so decrease body temperature in fever state.

Anti-Inflammatory: can reduce the inflammation of disease but not cure the disease

Others: dysmenorrhea (painful menstruation), patent ductus arteriosus, colon cancer (reduces risk).

Front 4

List general side effects of analgesic-antipyretic and anti-inflammatory agents.

Back 4

--GI ulceration,bleeding, perforation and intolerance = most common!

--block platelet aggregation (by inhibiting thromboxane syn)

--inhibit uterine motility (used to inhibit induction of labor)

--analgesic abuse nephropathy (primary lesion papillary necrosis w/ secondary chronic interstitial nephritis)

--hypersensitivity (asthma attacks, urticaria and angiodema, cross reactivity to all aspirin-like drugs)

Front 5

Which two side effects of nonselective COX inhibitors are NOT shared by selective COX-2 inhibitors?

a) inhibition of platelet function
b) alteration in renal funciton
c) inhibition of labor induction
d) GI ulceration and intolerance

Back 5

These 2 COX-1 inhibitor side effects are NOT shared by COX-2 inhibitors..
(a) inhibition of platelet function
(d) GI ulceration and intolerance

The other side effects (renal function inhibition and labor induction inhibition) are common to both COX-1 and COX-2 inhibitors.

Front 6

Aspirin

--mechanism
--uses
--contraindications

Back 6

Aspirin - NSAID prototype
-Salicylate

Mechanism: irreversible acetylation of COX. Effects on platelets persist for lifetime of platelet (8-10days)

Uses: analgesic, antipyretic, anti-inflammatory

(also juvenile RA, dec incidence of colon cancer & MI)

Contraindications: ulcer, gout, asthma, influenza (Reye's syndrome)

Front 7

Aspirin

--side effects
--signs of intoxication

Back 7

Aspirin

SE's: tinnitus, dec renal function, GI intolerance, hypersensitivity, hepatotoxicity

Salicylate Intoxication: respiratory alkalosis followed by metabolic acidosis, headache,dizziness, mental confusion, ringing in ears, drowsiness, sweating

Front 8

Diflunisal

Back 8

Salicylic acid derivative.
-greater anti-inflammatory effect than aspirin.
-No antipyretic effect
-Poor penetration into CNS
-Less auditory side effects than aspirin

Front 9

Diflunisal does not have which of the following effects:

(a) anti-pyretic
(b) anti-inflammatory

Back 9

(a) anti-pyretic

Diflunisal has no anti-pyretic effect but has a greater anti-inflammatory potency compared to aspirin.

Front 10

Mesalamine

(5-aminosalicylic acid)

Back 10

Salicylate used for its local effect in the treatment of inflammatory bowel disease.
-Oral preparation (Asacol) - used for ulcerative colitis

Front 11

This NSAID is used to treat IBD.

Back 11

Mesalamine

Front 12

Acetaminophen

Back 12

NSAID
-Tylenol
-Analgesic and antipyretic but weak anti-inflammatory agent.
-Well tolerated and lack many side effects of aspirin. Substitute for aspirin in pts with contraindications.
-Oral absorption, half life - 1-4 hrs, >4-6 g/d are not recommeded
-Adverse effects: Overdose (10-15 g/d) --> Fatal hepatic necrosis cue to toxic metabolite
-Chronic alcoholics have increased risk of toxicity.

Front 13

Of the following aspirin effects, which one is NOT shared by acetaminophen?

(a) anti-pyretic
(b) anti-inflammatory
(c) analgesic

Back 13

(b) anti-inflammatory

Acetaminophen is a weak anti-inflammatory drug.

Front 14

Give this antidote within 10 hours of acetaminophen OD..

Back 14

N-acetylcysteine

Front 15

Acetaminophen can be metabolized to these 3 non-toxic metabolites

Back 15

(1) sulfate
(2) glucoronide
(3) glutathione compound which is eventually converted to mercapturic acid

Front 16

This severe adverse effect can result from acetaminophen OD.

Back 16

fatal hepatic necrosis

Front 17

TRUE or FALSE

Chronic alcoholism can increase the risk of acetaminophen toxicity.

Back 17

TRUE

Chronic alcoholism induces P-450 enzymes, which is the key player in forming a toxic metabolite that can cause hepatic necrosis.

Front 18

Indomethacin

--uses
--adverse effects
--what drug inhibits indomethacin renal secretion?

Back 18

Indomethacin - NSAID

-Oral rapid/complete absorption. Half life 2-3 hrs

--tx: acute gout, ankylosiing spondylitis, management of patent ductus arteriosus (inhibit PG syn because PGs are whats keeping it open)

--adverse effects: GI- nausea, vomiting, anorexia, abdominal pain, CNS severe frontal headache, dizziness, confusion, depression

--probenecid inhibits renal secretion of indomethacin

Front 19

Sulindac

--uses
--rare complication

Back 19

Sulindac - NSAID - Indole derivative

-Prodrug --> active metabolite
-Less ulcerogenic potential, GI irritation and blood loss than aspirin

-Dose: 150-200 mg twice daily. Half life 7 hrs

--tx: rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute gout suppress polyp formation in colon cancer

Rare complication: renal stone

Front 20

Tolmetin

Back 20

NSAID - heteroaryl acetic acid derivative

-Adverse effects: GI (MC) - epigastric pain, nausea, vomiting, CNS - less common than indomethacin

-Ineffective in treatment of gout

Front 21

Diclofenac

Back 21

NSAID - heteroaryl acetic acid derivative
-Reduces both synthesis of PG and leukotrienes
-Oral
-Less likely than aspirin to cause peptic ulcer and GI bleeding

-Adverse Effects: GI (MC), Increased hepatic transaminase
-Contraindications: children, nursing mothers or pregnant women

Front 22

Ketorolac

Back 22

NSAID - heteroaryl acetic acid derivative
-First injectable NSAID
-mechanism of action: related to prostaglandin synthetase inhibition
-Used for short-term (<5 days) of moderately severe acute pain that requires pain relief at opioid level (w/ no addiction), used postoperatively

Front 23

These 2 drugs can reduce the synthesis of both prostaglandins and leukotrienes.

Back 23

1) diclofenac
(2) ketoprofen

These drugs inhibit both lipooxygenase and cyclooxygenase enzymes.

Front 24

This NSAID inhibits lipoxygenase and cycloxygenase and is not recommended for children, pregnant or nursing women.

Back 24

Diclofenac

(as a comparison, ketoprofen aslo inhibits lipoxygenase and cycloxygenase)

Front 25

This NSAID can be used short-term for moderate - severe pain.

Back 25

Ketorolac

Front 26

Ibuprofen

Back 26

NSAID - Motrin, Advil, Nuprin

-Mild anti-inflammatory and analgesic drug with reduced symptoms of gastric irritation
-Highly protein bound - metabolized in liver.
-Oral. Half-life 2 hours.
200 mg = OTC dose

Front 27

TRUE or FALSE

Ibuprofen has a more potent analgesic effect compared to its anti-inflammatory effect.

Back 27

TRUE

Larger ibuprofen doses are needed to produce anti-inflammatory effects

Front 28

Naproxen

--uses
--potency
--main route of elimination

Back 28

Naproxen - NSAID -Proprionic acid derivative

-Aleve, Naprosyn

-Oral, Long half-life (14hrs), taken twice daily
-Less GI irritation than aspirin
-Crosses placenta and appears in milk of lactating women

--tx: juvenile RA, acute gout, akylosing spondylitis, rheumatoid arthrits
--20x more potent than aspirin
--handled mainly by kidneys

Front 29

Name the 5 NSAIDs with (relatively) long half-lives.

Back 29

(1) naproxen -- 14hr
(2) meloxicam -- 20hr
(3) nabumetone -- 24hr
(4) oxaprozin -- 50hr
(5) piroxicam -- 55hr

Front 30

Ketoprofen

Back 30

NSAID - Propionic acid derivative
-Inhibits both cycolooxygenases and lipoxygenases (PG and Leukotrienes)

-Short half life (2hrs) take 3-4 a day
-Adverse effects: GI and CNS

Front 31

Oxaprozin

Back 31

NSAID - propionic acid derivative
-newer drug
-Very long half life (40-60 hrs)
-Once daily used for anti-inflammatory

Front 32

Piroxicam

Back 32

NSAID - Enolic acid
-structurally distinct from all other NSAIDs
-Very long half life (50-60 hrs)
-Potent reversible inhibitor of cyclooxygenase; nonselective COX inhibitor

Front 33

Meloxicam (Mobic)

Back 33

NSAID -Enolic acid
-Preferentially inhibit COX-2 over COX-1 (so less side effects)
-Half life 20 hrs
-Used for osteoarthritis

Front 34

This NSAID is structurally distinct from other NSAIDs and has a long half life.

Back 34

Piroxicam

Front 35

This NSAID inhibits COX-2 over COX-1 and treats osteoarthritis.

Back 35

Meloxicam

(as a comparison, nabumetone also preferentially inhibits COX-2; nabumetone however is a non-acid NSAID and it is also a prodrug)

Front 36

Nabumetone

Back 36

NSAID - alkanones
-Only nonacid NSAID
-Preferentially inhibits COX-2 at low doses
-Low incidence of side effects; GI ulceration much lower than other NSAIDs
-Half life 24 hrs

Front 37

This is the only nonacid NSAID. It preferentially inhibits COX-2 at low dose, but it is not purely selective.

Back 37

Nabumetone

Front 38

Nabumetone

Back 38

NSAID - alkanones
-Only nonacid NSAID
-Preferentially inhibits COX-2 at low doses
-Low incidence of side effects; GI ulceration much lower than other NSAIDs
-Half life 24 hrs

Front 39

Misoprostol

Back 39

Synthetic PGE1 analog
-used to prevent ulcers in people who take certain arthritis or pain medicines, including aspirin, that can cause ulcers. It protects the stomach lining and decreases stomach acid secretion.

-side effect: diarrhea

Front 40

This is the only nonacid NSAID. It preferentially inhibits COX-2 at low dose, but it is not purely selective.

Back 40

Nabumetone

Front 41

Celecoxib

Back 41

NSAID
-Selective COX-2 inhibitor
-Significantly fewer ulcers than naproxon or ibuprofen
-Used for osteoarthritis and rheumatoid arthritis
-Does not affect platelet aggregation or prothrombin time

Front 42

Misoprostol

Back 42

Synthetic PGE1 analog
-used to prevent ulcers in people who take certain arthritis or pain medicines, including aspirin, that can cause ulcers. It protects the stomach lining and decreases stomach acid secretion.

-side effect: diarrhea

Front 43

Abatacept

Back 43

Anti-rheumatic Drug
-selective costimulation modulator, inhibits T cell activation
-used for adult RA and juvenile idiopathic arthritis
-IV injection

Front 44

Celecoxib

Back 44

NSAID
-Selective COX-2 inhibitor
-Significantly fewer ulcers than naproxon or ibuprofen
-Used for osteoarthritis and rheumatoid arthritis
-Does not affect platelet aggregation or prothrombin time

Front 45

Rituximab

Back 45

Anti-rheumatic Drug
-Chimeric monoclonal antibody binds specifically to the antigen CD20 B lymphocytes
-IV injection
-Fatal infusion reactions have been reported

Front 46

Abatacept

Back 46

Anti-rheumatic Drug
-selective costimulation modulator, inhibits T cell activation
-used for adult RA and juvenile idiopathic arthritis
-IV injection

Front 47

List the 3 TNF-alpha blocking agents.

Back 47

(1) etanercept
(2) adalimumab
(3) infliximab

Front 48

Rituximab

Back 48

Anti-rheumatic Drug
-Chimeric monoclonal antibody binds specifically to the antigen CD20 B lymphocytes
-IV injection
-Fatal infusion reactions have been reported

Front 49

Etanercept

Back 49

TNFalpha blocking agent
-Antirheumatic drug
-binds specifically to TNF and blocks its interaction with cell surface TNF receptors
-Given SC twice weekly

Front 50

List the 3 TNF-alpha blocking agents.

Back 50

(1) etanercept
(2) adalimumab
(3) infliximab

Front 51

Adalimumab

Back 51

TNFalpha blocking agent
-Antirheumatic drug
-binds specifically to TNF and blocks its interaction with p55 and p75 cell suface TNF receptors
-Given SC every other week
-TB, invasive fungal infections and other infections have been seen in pts taking this

Front 52

Etanercept

Back 52

TNFalpha blocking agent
-Antirheumatic drug
-binds specifically to TNF and blocks its interaction with cell surface TNF receptors
-Given SC twice weekly

Front 53

Infliximab

Back 53

TNFalpha blocking agent
-Anti-rheumatic drug
-neutralizes activity of TNFalpha by binding w/ high affinity to the soluble and membrane bound TNF alpha and inhibits binding of TNF with its receptos
-Increased risk of infections
Given IV every 8 wks

Front 54

Adalimumab

Back 54

TNFalpha blocking agent
-Antirheumatic drug
-binds specifically to TNF and blocks its interaction with p55 and p75 cell suface TNF receptors
-Given SC every other week
-TB, invasive fungal infections and other infections have been seen in pts taking this

Front 55

Infliximab

Back 55

TNFalpha blocking agent
-Anti-rheumatic drug
-neutralizes activity of TNFalpha by binding w/ high affinity to the soluble and membrane bound TNF alpha and inhibits binding of TNF with its receptos
-Increased risk of infections
Given IV every 8 wks

Front 56

Inhibition of lipoxygenase prevents the formation of this molecule.

Back 56

leukotrienes

Front 57

The inducible COX-2 enzyme is involved in the formation of this molecule.

Back 57

prostaglandins

Front 58

The housekeeping COX-1 enzyme is involved in the formation of these 2 molecules.

Back 58

COX-1 involved in formation of:
(1) prostaglandins
(2) thromboxane

Front 59

Name the specific NSAID that would treat each of the following..

(1) short term moderate - severe pain
(2) IBD
(3) management of patent ductus arteriosus
(4) suppression of polyp formation in colon cancer
(5) RA without effect on prothrombin time

Back 59

(1) moderate-severe pain: ketorolac

(2) IBD: mesalamine

(3) patent DA: indomethacin

(4) suppress polyp formation: sulindac

(5) no effect on prothrombin time: celecoxib

Front 60

Why is adminstering N-acetylcysteine appropriate in the case of acetaminophen overdose?

Back 60

In the case of acetaminophen OD, metabolism by conjugation becomes saturated, and the drug is oxidatively metabolized by the CYP enzymes into a toxic metabolite.

N-acetylcysteine is a precursor of glutathione and as such, increases glutathione conjugation of the toxic intermediate. Thus, the toxic intermediate is converted to a glutathione-containing compound rather than a toxic adduct that causes hepatocyte apoptosis and/or liver necrosis.

Front 61

Which 2 NSAIDs and which anti-rheumatic drug would be appropriate for treatment of juvenile RA?

Back 61

Used to treat juvenile RA:

--aspirin
--naproxen
--abatacept

Front 62

Which NSAIDs would be appropriate for treatment of ankylosing spondylitis?

Back 62

Used to treat ankylosing spondylitis..

--indomethacin
--sulindac
--naproxen