Arthritis & Inflammatory Pain Flashcards by Tom Carroll

Acetaminophen

Acts centrally, 1ST LINE FOR PAIN MANAGEMENT IN OA

Same effectiveness as NSAIDs

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NSAIDs

No one better than others for arthritis and combining them doesn’t increase efficacy

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Lower doses of NSAIDs are for?

Analgesia

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Higher doses of NSAIDs are for?

Inflammation

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Topical NSAIDs have lower risk of GI AEs, but higher risk of derm AEs compared with oral and are indicated for individuals with?

Knee-only OA

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Only FDA approved topical NSAID for hand or knee?

Diclofenac gel 1%

Diclofenac sodium 1.5% is a solution for knee OA

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Local COX-2 enzyme inhibitors with a modest short term efficacy in treating OA?

Topical Salicylates (bengay, aspercreme)

AEs = pruritus, burning, pain, rash are common

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Drug isolated from hot chile peppers that depletes substance P from affront nociceptive nerve fibers?

Capsaicin

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Limited efficacy drug for muscle/joint pain, neuropathic pain from DM or postherpetic neuralgia that you must use regularly 4x/day for several weeks to see an effect?

Capsaicin (wash hands after applying)

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Triamcinolone or Methylprednisolone

Intro-articular corticosteroids typically used to decrease inflammation in OA and RA

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Problem with using intra-articular corticosteroids for OA (but maybe not RA) is that?

They can cause degradation of cartilage in OA

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PTs who don’t get pain relief with APAP/NSAIDs or topical therapy we try?

Opioids, one at a time, low dose, with lots of monitoring

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Partial Mu receptor agonist that inhibits serotonin/NE reuptake, used in OA for uncontrolled pain that can potentially lead to resp depression if person metabolizes really fast?

Tramadol

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Tramadol has a one big potential AE, which is?

serotonin syndrome

(Seizures have been seen and concurrent use with other serotonergic meds increases risk of seizures and serotonin syndrome)

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What is the list of opioid meds that are options for OA? There are 6

Hydrocodone
Oxycodone
Morphine
Hydromorphone
Fentanyl
Tramadol

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The two main dietary supplements in OA are?

Glucosamine and Chondroitin Sulfate (NOT FDA approved)

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Substance in cartilage that adds tensile strength, composed of glucosamine and aminosugars, increases intrarticular hyaluronic concentration and instrinsic viscosity, promoted to decrease cartilage-destroying enzymes?

Chondroitin Sulfate

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Glucosamine hydrochloride should not be used, why?

It hasn’t been studied

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Glucosamine and chondroitin appear to be safe and might help OA, except which big DI and what happened to rats that took them PO?

The DI is with warfarin and in rats they saw severe kidney problems

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IL-1 and TNF are the two cytokines that predominate in this form of arthritis that bilaterally usually affects small joints.

RA (can affect the entire body)

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What lab tests will likely come back elevated in an RA patient?

RF, CRP, ESR

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What four groups/individual drugs are generally used to manage RA?

NSAIDs (usually first)
Steroids
DMARDs
Duloxetine

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Pain/inflammation adjunct used in RA while waiting for DMARDs to kick in, but DO NOT ALTER DISEASE PROGRESSION?

NSAIDs

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What are the 4 preferred NSAIDs used in RA?

Ibuprofen
Meloxicam
Nabumetone
Naproxen

Obviously careful with GI issues

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What are the 3 commonly used corticosteroids in RA?

Methylprednisolone IV (more for acute RA) Prednisolone PO Prednisone PO

Are corticosteroids indicated for long term use in RA or more as an acute/bridge therapy?

Acute/bridge therapy...lots of AEs if used long-term

DMARDs are the TOC for RA, what are the 3 mainstays of treatment when starting these drugs?

Start w/i first 3 months of symptoms, early treatment = reduced mortality, TAKES WEEKS TO 3 MONTHS BEFORE BENEFIT IS SEEN (so you need a bridge therapy) use these in almost all RA pts, screen for hep B/C and TB prior to starting (commercials)

What are the 4 traditional DMARDs that are used?

Methotrexate Leflunomide Hydroxychloroquine Sulfasalazine

What are the 3 biological DMARDs that we use?

TNF-a inhibitors Non-TNF-a co-stimulation modulators Biosimilar DMARDs

Which DMARD is a dihydrofolate reductase inhibitor that interferes with DNA synthesis, repair, and cellular replication...considered the preferred and MC used traditional DMARD?

Methotrexate

Methotrexate is the initial DMARD therapy, then what can you do if there’s no response or partial response?

Add other agents This drug also treats psoriatic arthritis and improves the skin

What do you need to do daily for a patient on methotrexate, except on the it’s taken, in order to reduce AEs?

Add folic acid supplementation daily

What are some AEs and considerations when talking about methotrexate?

GI SEs are common Chronic use can lead to leukopenia and hepatic cirrhosis so need monitor CBC, platelets, AST/ALT METHOTREXATE IS A CATEGORY X FOR PREGNANCY

What is the methotrexate toxicity reversal agent?

Leucovorin (folinic acid) - can be used 24hrs after methotrexate to reduce AEs

Prodrug that inhibits pyrimidine synthesis, resulting in antiproliferative and anti-inflammatory effects in RA?

Leflunomide

When do we use Leflunomide?

When pts do not tolerate or respond to methotrexate, shown to be just as effective at reducing disease activity and progression

This med is still detectable in your system 2 years after stopping the med

Leflunomide Cholestyramine can be used to rapidly clear it in the event of severe toxicity

AEs and CIs for Leflunomide?

Severe liver injury and peripheral neuropathy are the two main ones (so monitor) LEFLUNOMIDE IS PREGNANCY CATEGORY X...so if you’re taking it and find out you’re pregnant, stop use and take cholestyramine to clear it

The only labeled use for this DMARD is as an anti-malarial, but it can be used off-label for RA and lupus.

Hydroxycholorquine

This DMARD is less effective than methotrexate, but also has less liver/immune effects than other DMARDs

Hydroxycholorquine

Hydroxychloroquine causes GI, Derm, and these specific ocular AEs

Black spots in the visual field, blurred vision, night blindness that MAY BE IRREVERSIBLE

DMARD that is a prodrug for 5-aminosalicylic acid, used for mild RA and UC...not as effective as other DMARDs.

Sulfasalazine Also GI SEs limit its use

This class of medications for RA are newer and act by blocking the pro-inflammatory cytokines TNFa, IL, or prevent co-stimulation needed to fully activate T-cells.

Biological DMARDs

When do we use biological DMARDs?

Pts who do not respond to a first line agent such a methotrexate or combo therapy OR in pts with poor prognostic indicators like extra-articular disease or functional limitation

What are the 3 biologic DMARDs that are TNFa inhibitors that we use?

Adalimumab (Humira) - Human IgG Ab to TNFa Infliximab (Remicade) - Chimeric Ab to TNFa Entanercept (Enbrel) - TNFa antagonist

These meds all can increase the risk of infection so can’t be initiated if the pt has any infection (especially TB) Also they all cause increased blood cancers in children and adults (BB warning) Cautious in pts with HF

Biologic DMARDs

A spectrum of disease that includes hyperuricemia?

Gout

Terminal step in the degradation of purines leads to the production of?

Uric acid, it’s a waste product, no physiologic purpose

What 6 groups of drugs predispose people to gout?

Diuretics, salicylates (so don’t use ASA in gout, use NSAIDs), calcineurin inhibitors, chemo drugs, niacin, xanthine oxidase inhibitors

What is the target serum urate level in gout?

Less than 6mg/dL (or 5 if symptoms/tophi present)

During gout, these three groups of meds are used acutely or as prophylaxis during ULT initiation

NSAIDs Colchicine Glucocorticoids

Urate Lowering Therapy that we use for chronic suppression (3 groups, 6 drugs)

``` Xanthine Oxidase Inhibitors (Allopurinol, febuxostat) Uricosuric agents (Probenecid, Lesinurad) Uricase (urate oxidase) - (Pegloticase, Rasburicase) ```

Gout treatment timeline

NSAIDs and Colchicine first (Colchine only if initiated w/i 36 hours of attack onset) If already on ULT, continue it, stop meds that cause hyperuricemia Acute severe attack...do above or Colchicine + oral corticosteroids but DON’T do NSAIDs w/ Corticosteroids due to GI AEs

Two best Gout NSAIDs for acute gout attack?

Naproxen and Indomethacin Can use Celecoxib (Celebrex) in pts w/GI precautions; will reduce but not eliminate risk of GI bleed

This drug binds to tubulin, only shown to be effective if onset is no greater than 36 hrs prior to treatment initiation, ONLY DRUG INDICATED FOR PROPHYLAXIS OF GOUT FLARES (doesn’t decrease urate levels, just sort of anti-inflammatory)

Colchicine

What are the issues with Colchicine?

Can’t give or adjust dose in renal/hepatic failure Most have some degree of GI SEs

Use these alone or in combo w/colchicine during acute gout attacks intraarticularly in effected joints

Corticosteroids

Triamcinolone

IM corticosteroid that can be used to initiative oral dose

For chronic management of Gout, use...

ULTs

Tophi, two or more gouty attacks per year, CKD stage 2 or worse, past urolithiasis

Indications for starting a ULT

What are the first line ULTs?

Xanthine Oxidase Inhibitors (XOI)

Allopuriol and Febuxostat

The two XOIs that are first line ULTs (prophylaxis with NSAIDs or colchicine is recommended upon initiation)

This XOI is more expensive, has a higher risk of thromboembolic events (than allopurinol), but also is better tolerated and more likely to achieve <6mg/dL uric acid level goal

Febuxostat

Precipitation of acute gouty arthritis, you MUST give prophylactic dose of either of these two things for the first 2-3 weeks of ULT administration

NSAIDs or Colchicine (but not ASA b/c ASA renders them ineffective) 2nd line if can’t use those; corticosteroids