Pharm of NSAIDs Flashcards by Elise Wolff

Excess __ in inflamed tissue causes s/s of inflammation.

PGs

How well did you know this?

Not at all

Perfectly

What class inhibits the inflammation at the site?

salicylate

How well did you know this?

Not at all

Perfectly

___-induced GI complicaitons dt effects on gastric mucosa?

NSAIDs

How well did you know this?

Not at all

Perfectly

Name of the four traditional NSAIDs

ibuprofen
naproxen
diclofeac
indomethacin

How well did you know this?

Not at all

Perfectly

Name of coxibs antiinflammatory drug

celecoxib

How well did you know this?

Not at all

Perfectly

Three salicylates

salicylate
diflunisal
aspirin

How well did you know this?

Not at all

Perfectly

COX-1 and COX-2 similarities (4)

Use same substrates (e.g. AA)
Make same products (PGs)
Have a role in inflammation
Both have a physiological role in RENAL FUNCTION

How well did you know this?

Not at all

Perfectly

Which COX is expressed in all tissues all the time and has a prominent role responding to physiologic stimuli?
Which is induced in response to a pathologic stimuli and has a distinctive role in the kidney?

COX1 expressed constitutively

COX2 induced in response to pathologic stimuli in the kidney

How well did you know this?

Not at all

Perfectly

Which PG amplifies erythema, edema, and pain induced by COX1 and then COX2 expression?

PGE2

How well did you know this?

Not at all

Perfectly

What class of antiinflammatory is competitive, reversible, nonselective inhibitors?

tNSAIDs and salicylates.

How well did you know this?

Not at all

Perfectly

Which tNSAID is prescription?

diclofenac

How well did you know this?

Not at all

Perfectly

Osteoarthritis, Bursitis, Gout ‘flare’, Ankylosing spondylitis, dysmenorrhea, HA - all are indications for what?

NSAIDs

How well did you know this?

Not at all

Perfectly

AE of tNSAIDs in the gut and why?

Ulcer dt inhibition of COX1 and PGE2

How well did you know this?

Not at all

Perfectly

AE of tNSAIDs in the blood and why?

Bleeding dt inhibition of COX1, TXA2

How well did you know this?

Not at all

Perfectly

AE of tNSAIDs in the kidneys and why?

Peripheral edema, increased BP dt PGE2, PGEI2, renal artery.

How well did you know this?

Not at all

Perfectly

tNSAIDs are contraindicated in what pts?

asthma, gut inflammation, infectious inflammation fever, and KIDNEY DISEASE

How well did you know this?

Not at all

Perfectly

What antiinflammatory class is competitive, reversible, COX-2 selective inhibitors?

Coxibs - CELECOXIB

How well did you know this?

Not at all

Perfectly

AE of coxibs

peripheral edema and increased BP (dt COX1/2 action in renal artery)

How well did you know this?

Not at all

Perfectly

If a pt has a sulfa allergy, do not give what antiinflammatory. Why?

Celecoxib is CI bc it can cause exfoliative dermatitis/SJS

How well did you know this?

Not at all

Perfectly

High dose aspirin is a prodrug for what. How is it metabolized?

Prodrug for an anti-inflammatory dose of salicylate. Metabolized by the liver.

How well did you know this?

Not at all

Perfectly

The following are COX-Independent toxicities of what two drugs: acid base disturbances, tinnitus, hypersensitivity, Reye’s Syndrome.

aspirin/salicylates

How well did you know this?

Not at all

Perfectly

Tinnitus is the salicylate effect for __dose of aspirin.

325mg - 6gm

Resp alkalosis –> metabolic acidosis, fever, dehydration: is the salicylate effect for __dose of aspirin.

What if shock and coma?

6-20 g

> 20g of aspirin.

Do not use aspirin in anyone with a fever who is less than ___yo. What could occur?

less than 19

Reye’s syndrome

antiplatelet is the effect for __dose of aspirin.

80-160mg

- At ___doses, aspirin is a prodrug of salicylates, a ___ COX inhibitor. - Aspirin itself is a _____ COX inhibitor - tNSAIDs are ____ COX inhibitors

- anti-inflammatory doses, reversible - irreversible - reversible

Why does aspirin have an effective antithrombotic effect?

Irreversible acetylation of COX. Platelets have no nucleus, so recovery requires platelet turnover. Platelet aggregation is inhibited (~3 days)

Aspirin should be used as a primary or secondary prevention of MI?

esp secondary - after MI has occurred.

If a person has heart disease, do not give what?

COX2 selective inhibitor (coxib)

does acetaminophen inhibit COX?

no, so NOT antiinflammatory, but yes anti-pyretic and analgesic

NSAIDs and COXIBs have what toxicity?

thrombotic toxicity.

COXIBS and acetaminophen are safe to use in a pt with...

GI issues

salicylates, NSAIDs, and COXIBS all have what toxicity?

renal

Salicylates and NSAIDs are nonselective or selective COX1/2 inhibitors?

Nonselective COX1 and COX2 inhibitors - Antiinflammatory, anti-pyretic, analgesic.

COXIBS are nonselective or selective COX1/2 inhibitors?

Selective COX2 inhibitors - Antiinflammatory, anti-pyretic, analgesic.

All____ have a black box warning for people with cardiovascular risks.

NSAIDs (except for aspirin)

Three analgesics and three anti-inflammatory agents for osteoarthritis.

Analgesics: acetaminophen, tramadol, codeine | Anti-inflmmatory - NSAIDs (tNSAIDs or coxib), Triamcinolone (CS)

Drug recommended for mild, symptomatic OA without inflammation

acetaminophen (analgesic, antipyretic,not anti-inflammatory)

Acetaminophen overdose: MOA

MOA: Glutathione is used up, so NAPQI is overproduced, resulting in irreversible cellular damage (centrolobular necrosis).

Course of action of acetaminophen overdose (0-24hrs, 24-72hrs, 72-96hrs)

0-24hrs: N/V/abdominal pain 24-72hrs: RUQ pain, evolving liver damage 72-96hrs: N/V/abdominal pain, AST/ALT elevation, coagulopathy, kidney failure, COMA and DEATH

Antidote for actaminophen overdose

N-acetylcysteine in first 24 hours to replenish glutathioine pool and directly trap NAPQI

If OA sx persist with acetaminophen, what drug next?

NSAID for 2 wks prn (better for severe pain)

**The only injectable NSAID.

Ketorolac (toradol)

Does Naproxen or ibuprofen have longer half life?

naproxen (14hrs) v. ibuprofen (2-4hrs)

how many NSAIDs should be given at one time?

only one, unless it's a cardioprotective use of aspirin

OA sx: acetaminophen doesn't work --> NSAIDs dont work --> now what? (four options before steroid)

1. a different NSAID OR 2. Diclofenac (NSAID) + misoprostol (PG to protect gastric mucosa) = arthrotec OR 3. Naproxen (NSAID) + esomprazole magnesium (PPI to protect gastric mucosa) 4. coxib only

What coxib was removed from marked bc of CV risk?

rofecoxib - bc it: 1. spares COX1, so platelets are allowed to aggregate 2. inhibits COX2, lessening PGI2 (decreased vasodialtion and increased platelet aggregation)

If NSAIDs fail, describe the anti-inflammatory steroids and its MOA

Triamcinolone - represses COX2 mRNA induction, resulting in less PGs formed

short term narcotic analgesics. MOA.

tramadol, codeine. Mu receptor antagonists. | Tramadol inhibits catecholamine uptake.

OA, other arthritides, bursitis, gout "flare", ankylosing spondylitis, dysmenorrehea, migraine - all are indications for using....

NSAIDs

When are NSAIDs contraindicated?

- Asthma - Gut inflammation (gastritis, colitis, pancreatitis, heaptitis) - Infectious inflammation fever (meningitis, endocarditis, sepsis, bronchitis, sinusitis, rhinorrhea)

gastric sparing sparing NSAIDs

Coxibs

COX-1, COX-2, or both: - gut - blood/platelets - renal artery - joint

- gut is COX-1; PGE2 - blood/platelets is COX-1; PGE2/TxA2 - renal artery is COX-1 and COX-2; PGE2 and PGI2 - joint is COX-1 and COX-2,

explain salicylate toxicity at high doses of aspirin.

1. Salicylates uncouple mito ox phos, so body thinks there is less ATP and in a hypoxemic state, so it hyperventilates. 2. Hyperventilation causes alkalemia by blowing off CO2 and prompts kidney to deplete bicarbonate. 3. Organic acids accumulate bc ATOP isn't generated, causing metabolic acidosis.