Pharmacology-NSAID Flashcards Preview

MSK II > Pharmacology-NSAID > Flashcards

Flashcards in Pharmacology-NSAID Deck (25)
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1
Q

What transcription factor is the “Jack of all trades” in inflammatory response?

A

NF-kB

2
Q

How do leukotrienes get out of membrane layers?

A

Phospholipase A2 releases Arachadonic Acid. Lipoxygenases then form leukotrienes.

3
Q

How does thromboxane A2 come from a phospholipid membrane?

A

Phospholipase A2 releases arachadonic acid. Cyclooxygenase 1 & 2 form PGH2 which can become thromboxane A2 in platelets.

4
Q

Where do corticosteroids act?

A

Phospholipase A2 and COX 1. They also inhibit NF-kB signaling and thus COX-2 signaling.

5
Q

Why do NSAIDs not inhibit leukotrienes?

A

Leukotrienes do not cyclize

6
Q

Before an inflammatory response what arachadonic altering enzymes do you expect to find in tissue?

A

COX-1. It is constitutively expressed and produces low PG levels where COX-2 is induced by NF-kB and produces high PG levels

7
Q

Why must patients stop taking aspirin 7 days prior to a procedure and ibuprofen only 2 days before?

A

Aspirin irreversible binds COX enzymes where ibuprofen reversibly binds them.

8
Q

What GI toxicities come with long term NSAID usage? How can you alleviate these toxicities?

A

Dyspepsia (indigestion), ulcers, inflammation, erosion and hemorrhage. You can alleviate these with prostaglandins and proton pump inhibitors.

9
Q

What kidney toxicities come with long term NSAID usage?

A

Decreased glomerular filtration rate, edema, necrosis, nephritis and hyperkalemia.

10
Q

What other toxicities aside from GI and kidney effects come with NSAIDs?

A

Hypertension, hypersensitivites, CNS toxicity and impaired hemostasis.

11
Q

What are the short and long half life NSAIDs?

A

*

12
Q

Where are most NSAIDs bound when taken orally?

A

Plasma proteins

13
Q

What NSAIDs are nonspecific and COX2 specific?

A

Nonspecific = Aspirin, Ibuprofen, Naproxen, Flurbiprofen. COX2 = Celecoxib

14
Q

How do people who overdose on Tylenol usually die?

A

CYP2E1 breaks it down in the liver. If you produce too much NAPQI you use up all of the glutathione in the liver and toxic metabolites accumulate. People die of liver toxicity.

15
Q

A child and his pregnant mother come to you with a cold and a fever. They ask if they can take NSAIDs to relieve fever. What do you tell them?

A

To the kid, No. He could get Reye’s Syndrome. To the pregnant mom, No. It could cause premature closing of the ductus arteriosus. Both should use acetaminophen.

16
Q

Why do a lot of old people take a baby aspirin every day? What risks do they accept by taking aspirin every day?

A

Taking it daily has shown a reduction in MI and reduced incidence of cancer. They accept the risk of increased bleeding and stroke.

17
Q

Why would you recommend daily aspirin over ibuprofen to someone who has a history of blood clots?

A

Ibuprofen inhibits COX 1 and COX 2, so although inhibited, the balance between prostacyclin and thromboxane A2 effects stays the same. Low dose aspirin only inhibits COX 1 so you get less platelet aggregation and continued prostacyclin function (vasodilation). Ideally you would prescribe acetaminophen.

18
Q

Why might celecoxib cause cardiovascular problems?

A

Inhibition of COX-2 only decreases vasodilation by prostacyclin and throws of the balance with thromboxane A2 from still functioning COX-1.

19
Q

What type of inhibitors are more likely to have GI risk?

A

COX-1 inhibitors.

20
Q

What must you prescribe in addition to NSAIDs to someone with rheumatoid arthritis?

A

DMARDs (Disease modifying anti-rheumatic drug). TNF-alpha blockers and immunosuppressants (methotrexate).

21
Q

Why do gold salts help with rheumatoid arthritis?

A

The slow down macrophage movement and minimize their damage.

22
Q

How do you limit lymphocyte destruction in rheumatoid arthritis?

A

Leflunomide. It inhibits pyrimidine synthesis and has a very long half life. Hepatotoxic. Rituximab inhibits B cells. Abatacept inhibits T cells.

23
Q

What are the different TNF-alpha blockers?

A

Etanercept (binds TNF-alpha), Infliximab (TNF-alpha Ab and blocks stimulation by TNF-alpha), Adalimumab (Similar to infliximab but is a more human Ab).

24
Q

What side effects come with TNF-alpha blockers?

A

Increased incidence of infection and tumors.

25
Q

What RA drugs limit macrophages via IL-1 receptor stimulation pathways?

A

Anakinra (binds to IL-1 receptor and blocks IL-1 stimulation), Anti-IL 1 Ab, and Rilanocept (monoclonal Ab that mimics IL receptor)