Rheumatoid Arthritis
 Randoms
o Autoimmune inflammatory disorder
o 3x more in women than men
o Usually appears in 3rd or 4th decade
o Can become really debilitating, quite painful
o Can do surgery to try and pin fingers and correct it, but is not the first choice of treatment
o Joints become swollen, tender, and warm
o If you can stop the inflammatory process you can slow the destruction of the joints
o RA tider is test looking for antibodies specific to RA
o In the joints we have synovial fluid which lubricates it, keeps it moving smoothly. This is effected by RA
and caused pain
o Systemic effects like fever, weakness, fatigue, weight loss, thinning of skin, scleritis (inflammation in the
sclera), corneal ulceration, vasculitis.
 If people have vasculitis there is probably something autoimmune-wise in their body
o Osteoarthritis should not be confused with this. No systemic effects, kind of a natural part of ageing
 Patho
o Symmetric joint stiffness, pain, more intense in the morning
o Joints become swollen, tender, and warm
o Systemic
 eye, pulmonary disease, pericarditis
o fatigue, anorexia, weakness
 Overview of Therapy
o Relieve symptoms
 Pain, inflammation, and stiffness
 Also lifestyle modification (physical therapy, exercise, surgery for joints if they need it, may
remove diseased synovium), can do tendon repair if tendons are affected, can use plastic
implants for these guys
o Maintain joint function and range of motion
o Manage systemic involvement
o Delay disease progression
 This is a main goal with progressive diseases. Keep them from getting to the end stages as long
as we can
 Antiarthritic Drugs
o Non-steroidal anti-inflammatory (NSAIDs)
 Provide symptomatic relief but do not slow progression. They are efficient, have a rapid onset,
and are relitively inexpensive. Both analgesic and anti-inflammatory actions
o Glucocorticoids (adrenal corticosteroids)
 Very potent anti-inflammatory agents. May be able to slow progression of disease (as well as
relieve symptoms). Can be given systemically or injected into specific joints. Always use these
guys short term if possible because they cause adrenal atrophy, set us up for infection,
osteoporosis, and hyperglycemia (cause they increase blood glucose levels). Most common are
prednisone and prednisolone used for RA. If the pt has a fungal infection, they won’t be treated
with these because it will worsen the fungal infection. Always increase dose when the body is
under stress.
o Disease-modifying antirheumatic drugs (DMARDs)
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Reduce joint destruction and they slow disease progression. Usually when the process is acute
these meds will be started within a few months of the diagnosis. They take several months to be
effective (that’s why we start giving them early. Don’t use in acute process, considered for
chronic and prophylactic use). Monitor clients closely b/c they are considered toxic
Cyclooxygenase
o Cox-1: Housekeeper (goes to all tissues)
o Inhibition of Cox-1 can cause
 Gastric erosion and ulceration
 Bleeding tendencies
 Renal impairment
 Can reduce platelet aggregation when you’re on a Cox 1 inhibitor (good for cardiac people, like
when we give them aspirin)
o Cox-2 (goes to the tissue that is impaired)
 Inhibition of Cox-2 is mostly beneficial
 Suppression of inflammation
 Alleviation of pain
 Reduction of fever
 Supports renal function (important to watch renal failure people if we give them a Cox 2
inhibitor)
NSAIDs
o First Generation Prototype: naproxen (Naprosyn)
 Adverse Effects: GI disturbances, renal function compromise, increase risk of MI and stroke,
bleeding time prolongation
 Contraindications: PUD, bleeding dyscrasias
 Be careful in hemorrhagic stroke people (don’t want to cause more bleeding)
 Watch when taking with any other antiplatelet
 Dosage: 250-500 mg twice daily
o Second Generation Prototype: celecoxib (Celebrex)
 MOA: selectively inhibits COX-2 (can also inhibit Cox 1 but if it’s within therapeutic range it’s
only Cox 2)
 Adverse Effects: dyspepsia, abdominal pain, risk of cardiovascular event
 Contraindications: heart disease, CABG surgery, caution in dyslipidemia, HTN, DM, renal
impairment, sulfonamide allergy, pregnancy
 Dosage: 100-200 mg twice a day
 These are reserved to people with GI bleeds and any one who can’t tolerate a first generation
NSAID
 Will relieve joint pain, stiffness, and inflammation.
 Does contain a sulfa molecule (need to know if people are allergic to sulfa)
 Can mess with fetal heart, so any preggers shouldn’t take this med.
DMARDs I
o Prototype: methotrexate (Rheumatrex, Trexall, others)
 MOA: inhibits dihydrofolate reductase and lymphocyte proliferation
 Adverse Effects: blood dyscrasias (occur because this drug causes bone marrow supression, ex
thrombocytopenia, leukopenia, neutropenia), hepatotoxicity, nephrotoxicity
 Contraindications: pregnancy (causes fetal demise), liver disease
 Dosage: 7.5-25 mg PO/IM every week
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For long term RA DMARD 1 is the first choice
Has a low cost. Therapeutic affects will occur in 3-5 weeks. DMARD 1 is the fastest of all the
DMARDs
 When seen in oncology you’ll see much higher doses. They’re trying to stop the body from
destroying itself in this case
 This med blocks the synthesis of folic acid which inhibits the replication of rapidly dividing cells
 Most concered with liver disease people and renal disease people, starting with renal
insufficiency
 Can cause GI ulceration and if it does cause this they are going to stop the medication. Dr. can
order a PPI or H2 agent (like pepsid) for these guys to prevent this from happening. Used
prophylactically they have a better outcome when treating these. Also take these guys with a
full glass of water to prevent GI distress
 Hepatotoxicity = jaundice, fatigue, dark urine, anorexia, itchy skin, ascites. If we see these then
we know the person is in trouble
 Make sure to give women of child bearing age taking this med 2 forms of birth control. Also, we
have to give them a pregnancy test before starting them on this med
 Monitor LFT’s, renal function, CBC, platelets
 Client should report anorexia, abdominal fullness, jaundice
 Take with food or full glass of water
 May require prophylactic use of PPI
 Avoid use during pregnancy
 Use adequate contraception during pregnancy
Prototype: hydroxychloroquine (Plaquenil)
 MOA: Inhibits rheumatoid factor, acute phase reactants, and many enzymes
 Good for the milder symptoms, sometimes they combine this with the methotrexate.
 Plaquenil alone won’t stop disease progression. Sometimes it’s used for joint pain/stiffness that
occurs with Lupus
 Has a late onset and is often combined with an NSAID or steroid (so they don’t feel shitty until
the drug starts working)
 Adverse Effects: retinal damage
 Make sure and monitor their visual acuity. Tell them to go to an eye dr. to get checked out,
report any s/s of visual changes, even if it’s just a little bit of blurring, whatever. The sooner you
get on that the better…
 If retinopathy sets in it can be permanent and can cause blindness
 Risk of retinal damage increases as the dose increases. The higher the dose the higher the risk.
 If they complain of blurred vision, you should tell them to stop taking the med immediately
 Contraindication: retinal or visual field changes, pregnancy
 Dosage: 200 mg bid or 400 mg once daily
Prototype: sulfasalazine (Azulfidine)
 MOA: Exact MOA unknown (but they theroise that it affects 5-aminosalacylic acid (5-ASA)
 Reduced inflammation by suppressing prostaglandin synthesis and it also suppresses migration
of the inflammatory cells that go to the affected area. As it’s name indicates, anyone with a sulfa
allergy should not take this medication (or if you have an aspirin allergy don’t take it)
 Adverse Effects: GI, anorexia, diarrhea, hepatitis, bone marrow suppression
 Don’t give to people who are already immunosuppressed shouldn’t have these meds
 Can cause macrocytic and hemolytic anemias
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Contraindications: sulfa and salicylate allergies
Dosage: 2 g/day in divided doses
Enteric-coated preparations in divided daily doses help diminish GI symptoms
Monitor liver function tests, CBC, and platelet counts
Tell them to tell us if they have any kind of GI irritation going on
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Immunosuppressive agents
Target specific components of inflammatory process
Kind of a newer therapy
Four currently available
 Etanercept (Enbrel)
 Infliximab (Remicade)
o These first two cause injection site irritation (main AE)
o May complain of redness, itching, or redness at the site. If this occurs the meds
should be stopped.
 Adalimumab (Humira)
 Anakinra (Kineret)
 These meds are biologic agents and are also listed as tumor necrosis blockers.
 These meds pose an increased risk for infection and if you start seeing any s/s of
infection (fever, chills, sore throat, etc.) tell someone…
DMARDs II
o Info
DMARDs III
o Prototype: lefunomide (Arava)
 MOA: inhibits T-cell proliferation
 Adverse Effects: hepatotoxicity, severe HTN, respiratory infection, diarrhea
 Contraindications: pregnancy, severe infection, concurrent live vaccination
 Dosage: 10-20 mg/day
 These guys can inhibit the metabolism of NSAIDs. This will cause toxicity (we look at liver if this
happens).
DMARDs IV
o Prototype: Gold Salts (has been around since the 1930’s)
 Gold can relieve pain and stiffness
 MOA: exact MOA unknown, suppresses synovitis (the inflammatory process/irritaion that
happens in the synovial fluid)
 May arrest the progression of the joint degeneration, but probably not as effective as other
agents
 Adverse Effects: intense pruritus (most common), stomatitis, renal toxicity, blood dyscrasias
(monitor CBC, WBC), hepatitis, GI stuff (N/V and abd pain)
 Contraindications: heavy metal toxicity (serious)
 They save this treatment for those people who don’t respond or are unable to take any
of the other DMARDs
 Take 4-6 months to have a therapeutic response
 How do we know if our kidneys are being affected negatively by these guys? We’ll see some
proteinurea. If we see any of these toxicities this medication must be stopped
 Might see bleeding and bruising in the gums if they have dyscrasia. Teach to use soft tooth
brush and don’t shave
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Gout
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Info
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Stop medication and call primary care provider if intense pruritus, rashes, or mouth ulcerations
develop
Monitor I & O, BUN, creatinine, and UA
Monitor CBC, WBC, and platelet count
Observe for signs of bruising and bleeding of gums
Monitor LFT’s
Problem with uric acid metabolism
Hallmark is hyperuricemia
Characterized by Defective purine (found in foods) metabolism
 attacks of acute pain, swelling, tenderness of joints (big toe, most common site)
 tophi – deposits of uric acid or urates (crystalized). These crystals will increase in size and you
see them most often along the edge of the ear.
o Caused by an accumulation of uric acid that increases the production/ or inhibits the excretion of uric
acid
o When you’re having an attack of gout the uric acid level in the blood is elevated along with the tophi
Purine Foods
o Low Purine Foods
 Green veggies and tomatoes, fruit and fruit juices, breads that do not use yeast (unlevined
breads, kosher crap), nuts, milk and milk products such as butter and cheese, chocolate, coffee
and tea
o High Purine Foods
 Alcohol, meats (beef, pork, bacon, lamb), seafood (scallops), anything with a specific amount of
wheat in it, like beer and breads and what not. Asparagus, cauliflower, mushrooms, peas,
spinach, whole grain breads and cereals, white poultry meats (chicken, turkey, duck), and also
kidney and lima beans.
Risk Factors for Gout
o Obesity
o Hypertension
o Lead exposure
o Drugs
 thiazides, aspirin, alcohol, cyclosporine
 These increase your risk for gout, can interfere with uric acid excretion. If you have a patient
with hyperuricemia and their on one of these agents they’ll be on gout medication
Drugs that Increase Uric Acid
o ACE inhibitors
o Alcohol (and turkey and ham at thanksgiving and Christmas are prime times for flare ups)
o Aminoglycosides (gentomycin)
o Diuretics
o Cancer chemotherapy agents
Drug Therapy
o Prototype: Colchicine
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MOA: decreases leukocyte lactic acid production and phagocytosis of urate crystals resulting in
↓ uric acid deposition and ↓ inflammatory response
 Specifially treats the inflammation that occurs with gout. Take this in an acute phase, if you’re
having symptoms you take this. It’s an alkaloid derivative.
 Metabolized by P450 so it can accumulate with no inhibitor (like grapefruit juice). Teach patient
to not take this with grapefruit juice. The “azoles” will also cause this to accumulate.
 Dose of 0.6 mg for prophylaxis (3 times a day?)
 Dose of 0.6 mg every one to two hours during an acute attack
 Adverse Effects: nausea, vomiting, abdominal Pain, diarrhea
 If the AE’s are really severe the medication should be stopped. To decrease the effects
of GI crap you take the medication with food.
 Contraindications: hepatic & renal impairment, severe GI tract disorders
 Can cause fetal harm, careful when giving to preggers
 This slows the metabolism of Coumadin increasing the risk of hemorrhage when taken together
Probenecid (Benuryl)
 Sulfonomide derivitive
 Increases urinary excretion of uric acid, and will lower serum uric acid levels
 Can prevent or resolve those urate deposits (that cause those tophi bitches in your ear/elbow)
 Take with food
 Course of therapy not to be repeated within 3 days; very narrow margin of safety
 No alcohol & avoid high purine foods
 Alkalinize the urine
 Encourage intake of 2-3 liters of fluids daily
 Stop medication is severe GI symptoms occur
 You take it at the first sign of the attack, but as soon as you start having relief of symptoms you
stop taking the drug. Need to notify dr at the first signs of N/V/D, sore throat. This is telling you
that you maxed out your dose and you’re going to have toxicity, you need to get ahold of you dr
Prototype: allopurinol (Zyloprim) (used for prophylaxis tx of Gout)
 MOA: inhibits xanthine oxidase, interfering with conversion of hypoxanthine and xanthine to
uric acid. Will decrease uric acid in urine and serum. Helps to prevent attacks, but does not
relieve acute episodes of gout.
 Xanthine is an enzyme required to form uric acid
 Adverse effects: Skin rash, bone marrow suppression, hepatotoxicity, renal failure
 Contraindications: caution in impaired renal and/or liver function
 Concerned most with old people, we’ll see that all of a sudden this older person has
thrombocytopenia. It was the allopurinol causing this, not cancer…
 Dosage: 100-200 mg bid or tid or 300 mg once daily
 No alcohol
 Increase fluids (water and fruit juices are good)
 Maintain a diet that enhances alkalinity of urine
 Alkaline urine puts you at risk for UTI’s, esp old people. This is the only kind of
stone/crystal or whatever that needs alkaline pee
 Notify for side effects
 Have uric acid levels checked
 Monitor PT/INR and report symptoms of bleeding if on Coumadin
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Slows the metabolism of Coumadin, monitor PT, INR if they are on coumadin. May
require a dose change