NSAIDs and DMARDs Flashcards by Kelly Weaver

How do prostaglandins potentiate pain?

They potentiate the stimulation of nerve endings produced by histamine or bradykinin (these cause pain)

How well did you know this?

Not at all

Perfectly

What does pyrogen do?

Stimulate prostaglandin production in the hypothalamus, which increases body temperature (fever)

How well did you know this?

Not at all

Perfectly

What are the GI side effects of NSAIDs?

Dyspepsia
N/V
 blood loss
 ulcer
 GI hemorrhage

How well did you know this?

Not at all

Perfectly

How can you decrease GI side effects of NSAIDs?

Administer w/food

How well did you know this?

Not at all

Perfectly

What causes GI side effects?

NSAIDs are acidic
NSAIDs inhibit PGE2, which is cytoprotective in the gastric mucosa
NSAIDs inhibit platelet aggregation –> bleeding

How well did you know this?

Not at all

Perfectly

What can be used to decrease hypersensitivity from NSAIDs?

Lipoxygenase inhibitors–hyposensitivity caused by leukotrienes

How well did you know this?

Not at all

Perfectly

What disease state is more likely to have hypersensitivity to NSAIDs?

Asthma

How well did you know this?

Not at all

Perfectly

What is Reye’s syndrome?

A rare, acute, life-threatening condition characterized by vomiting, delirium, and coma

How well did you know this?

Not at all

Perfectly

Who is at risk for Reye’s syndrome?

Children (<12) who have flu or chicken pox

How well did you know this?

Not at all

Perfectly

What class of NSAIDs causes Reye’s Syndrome?

Salicylates

How well did you know this?

Not at all

Perfectly

What are the CNS side effects of NSAIDs?

Tinnitus
Dizziness
Headache

How well did you know this?

Not at all

Perfectly

Who is at risk for renal failure from use of NSAIDs?

Patients with cardiovascular, hepatic, and renal diseases

How well did you know this?

Not at all

Perfectly

Order of side effect frequency of aspirin, indomethacin, naproxen, and sulindac?

Aspirin = indomethacin > naproxen > sulindac

How well did you know this?

Not at all

Perfectly

What two drugs are used to prevent GI side effects with NSAIDs?

PPIs and misoprostol

How well did you know this?

Not at all

Perfectly

What is misoprostol?

PGE1 analog–mucus protectant

How well did you know this?

Not at all

Perfectly

Why is naproxen used in combination products?

It has fewer side effects than other NSAIDs

How well did you know this?

Not at all

Perfectly

What causes the drug interactions associated with NSAIDs?

NSAIDs are highly bound to albumin

How well did you know this?

Not at all

Perfectly

What class of drugs commonly interacts with NSAIDs?

anticoagulants

How well did you know this?

Not at all

Perfectly

What should be done to anticoagulant dosing when administered with NSAIDs?

Decrease (NSAIDs compete for albumin, which causes more free anticoagulant in the blood PLUS NSAIDs are already antithrombotic)

How well did you know this?

Not at all

Perfectly

What functional group do most NSAIDs have?

Carboxylic acid

How well did you know this?

Not at all

Perfectly

Where is the acidic group located in salicylates?

Directly off of the carbon ring

How well did you know this?

Not at all

Perfectly

Where is the acidic group located in arylacetic acids and arylpropionic acids?

1 carbon between the acid and the ring

How well did you know this?

Not at all

Perfectly

What is the structural difference between arylpropionic acids and arylacetic acids?

Arylpropionic acids have an alpha methyl group on the carbon next to the COOH

How well did you know this?

Not at all

Perfectly

What does a methyl group on the carbon atom separating the acidic group from the aromatic ring due to activity levels?

Increases

How well did you know this?

Not at all

Perfectly

What does a second area of lipophilicity that is noncoplanar with the aromatic ring due to activity levels?

Enhances

What was the first salicylate derived from?

Willow and poplar bark

What form are salicylates absorbed in?

Ionic in small intestine mainly, also unionized in stomach

What enzyme do salicylates inhibit?

COX-1 and COX-2

What are the three salicylates?

Aspirin Salsalate Diflunisal

How does aspirin irreversibly inhibit COX?

Acetylates a serine residue in the active site

What is aspirin hydrolyzed into?

Salicylate

How does aspirin reduce the risk of MI?

It blocks TXA2--which causes platelet aggregation?

Is aspirin found in solution form?

No--not stable

What is the structure of salsalate?

Dimer of salicylic acid?

Does salsalate cause GI bleeding?

No--not active in the stomach b/c it needs to be cleaved

Where is salsalate get hydroylzed?

small intestine

Is diflunisal a more potent alangesic than aspirin?

Yes

Is diflunisal a more potent antipyretic than aspirin?

Does diflunisal have fewer side effects than aspirin?

yes

Does diflunisal have a longer half-life than aspirin?

Yes (3-4 times)

What are the arylacetic acids?

Indomethacin Sulindac Etodalc Diclofenac

Which arylacetic acids are somewhat selective for COX-2?

Etodalc and Diclofenac

Which arylacetic acid inhibits both COX and lipoxygenase pathways?

Diclofenac

Which arylacetic acid is a prodrug?

Sulindac--sulfoxide group reduced

What is the least potent arylacetic acid?

Sulindac

Which arylacetic acids can be used for long-term use?

Sulindac, etodalc

Which arylacetic acids have lesss GI side effects?

Sulindac (prodrug) | Etodalc (COX-2 selective)

Which aryacetic acid is not stable in solution due to hydrolysis of the amide bond?

Indomethacin

Which arylacetic acid has high incidents of side effects?

Indomethacin

What is the most commonly used NSAID?

Diclofenac

What is etodalc used for?

Osteoarthritis

What is sulindac used for?

Chronic inflammation

What are the arylpropionic acids?

ibuprofen, naproxen, ketoralc

Which of the arylpropionic acids is a racemic mixture?

Ibuprofen

How does ibuprofens potency compare to aspirin and indomethacin?

In between them

Is naproxen or ibuprofen more potent?

Naproxen

What is naproxen used for?

Rheumatoid arthritis and osteoarthritis

What is the structure of ketorolac?

Cyclized heteroarylpropionic acid derivative

What is ketorolac used for?

Short term management of severe pain (as strong as an opioid)

What are the non-carboxylate NSAIDs?

Nabumetone | Meloxicam

What is the active form of nabumetone?

6-MNA

What is nabumetone good at?

Anti-inflammation (weak analgesic activity)

Does nabumetone have many gastric side effects?

Nope (prodrug)

Which NSAID is longest acting?

Meloxicam

How does meloxicam's potency compare to aspirin and indomethacin?

About as potent as indomethacin

Which of the non-carboxylates is selective for COX-2

Meloxicam

What are the most potent anti-inflammatory NSAIDs?

Meloxicam Indomethacin Diclofenac Sulindac

what are the safest and most potent NSAIDs?

Meloxicam | Diclofenac

What is the least potent NSAID?

Aspirin

What is the difference between the COX-1 and COX-2 active site?

COX-2 has a valine instead of isoleucine--makes it a larger active site

How are COX-2 selective inhibitors structurally different from non-selective?

They have larger and more rigid functional groups (b/c COX-2 has bigger binding site)

What are the 3 FDA classified COX-2 Inhibitors?

Celecoxib Rofecoxib Valdecoxib

What is the only selective COX-2 inhibitor still in market?

Celecoxib (Celebrex)

How do selective COX-2 inhibitors increase the risk of cardiovascular events?

They inhibit PGI2 (inhibiting platelet aggregation) but not TXA2 (which causes platelet aggregation)--> increased risk of clots (strokes, MIs, etc)

What drug is celebrex's potency similar to?

Naproxen

What is celecoxib used for?

Rheumatoid arthritis Osteoarthritis Pain/inflammation/fever

What does acetaminophen do?

Reduce pain and fever (not inflammation)

How does acetaminophen work?

It scavenges peroxynitrite which is required for PGHS (COX)--only works with low levels of peroxynitrite, not during inflammation when levels are high

What is the major caution with acetaminophen?

Hepatotoxicity

What causes hepatotoxicity from acetaminophen?

It is made into N-acetylmidoquinone by CYP450, which is reduced by glutathione, Too much APAP means more is made, which means more glutathione is used. Glutathione is needed for cells, so this causes cell damage in the liver

What can make acetaminophen toxicity worse? How?

Alcohol--induces CYP450 enzyme so more N-acetylmidoquinone is made form APAP more quickly

How long do DMARDs take to act?

1 to 6 months

What is the common mechanism of action of DMARDs?

Immunosuppression

What are the 3 uses for DMARDs?

Rheumatoid arthritis Inflammatory bowel disease Reduce rejection in organ transplant

WHat is the first line treatment of RA?

Methotrexate

What is the MOA of methotrexate?

Inhibits ribonucleotide transformylase and thymidylate synthetase to decrease purine and pyrimidine synthesis

What are side effects of methotrexate?

Gi symptoms, stomatitis, rash, hair loss Myelosuppression (decreased bone marrow activity) Hepatotoxicity Pulmonary toxicity

When is methotrexate contraindicated?

Pregnancy

What is the MOA of leflunomide?

Pyrimidine synthesis inhibitor and T cell proliferation inhibitor

What are the side effects of leflunomide?

Heptotoxicity, diarrhea, hair loss, rash

What should you monitor when taking leflunomide?

Hepatotoxicity

When is leflunomide contraindicated?

Any women of childbearing age

Is leflunomide a prodrug?

Yep

What is hydroxychloroquine?

Protein secretion inhibitor--in lysosomes

What should be monitored when taking hydroxychloroquine?

Opthalmologic monitoring for reversible retinal toxicity

What does sulfasalazine do?

Suppress release of cytokines from macrophages

How long does sulfasalazine take to work?

Several months

What needs to be monitored with sulfasalazine use?

myelosuppression

What are the active components of sulfasalazine?

sulfapyridine and 5-aminosalicylic acid

What is infliximab?

TNF blocker--chimeric

How is infliximab given?

IV every 8 weeks

What is adalimumab?

Human antibody to TNF-alpha

How is adalimumab given?

Subcutaneously every 2 weeks

What is etanercept?

TNF-alpha receptor antibody (competitively inhibits TNF-alpha)

What is the IL-1 receptor antagonist?

Anakinra

Can anakinra be used with TNF blockers?

What is rituximab?

Monoclonal antibody against CD20--induces apoptosis of B cells Blocks activation of T cells

When is rituximab used?

With methotrexate if TNF-alpha blockers don't work

What is the risk with rituximab?

Serious infection (antibody production decreases)

What is abatacept?

Fusion protein of cytotoxic T-lymphosyte associated protein 4 (CTLA4) and FC region of human antibody

How does abatacept work?

It mimics CTLA4 to bind to CD80 on APCs, thereby preventing activation of T cells

Can abatecept be combined with TNF-alpha blockers?

What are the side effects of abatacept?

Risk of serious infection | Risk of lymphomas

NSAIDs and DMARDs Flashcards

(113 cards)