Msi Week 3: Treatments Of Rheumatological Diseases

Front 1

the goals of rheumatologic treatments include:
relieve ______
decrease_________
prevent ___________
address ____________
tailor to ___________

Back 1

relieve pain
decrease inflammation
prevent deformities
address extra-articular involvement
tailor to individual

Front 2

This type of treatment has rapid onset of effects and it is not disease specific but used for many rheumatologic conditions

Back 2

symptomatic treatments

Front 3

This type of treatment is often immunosuppressive and/or anti-inflammatory with sower onset of effects and can be divided into traditional, non-biologic, and biologic agents

Back 3

disease modifying treatments

Front 4

What are the symptomatic treatments?

Back 4

acetaminophen
salicylates
NSAIDs
codein, opiods
Tramadol
Topic analgesics
Corticosteroids (may also be disease modifying)

Front 5

What does DMARD stand for?

Back 5

disease-modifying anti-rheumatic drugs

Front 6

What is used in RA for short term control "bridge therapy" while awaiting the affects of slow-acting drugs?

Back 6

oral prednisone

Front 7

Oral prednisone in high doses is usually required at first for what?

Back 7

systemic autoimmune diseases

i.e. SLE, polymyositis, vascultits

one control of activity is achieved the dose is tapered.

Front 8

What are the long term side effects of using prednisone?

Back 8

infection
diabetes
hypertension
cushing's syndrome

Front 9

Very high dose regimens of this are sometimes used as initial treatment for severe disease, such as lupus nephritis

Back 9

pulsed dose methylprednisolone

Relatively high doses of intramuscular methylprednisolone are sometimes used as initial treatment to supplement low-dose steroids in RA

Front 10

What is injected into the joints, bursae, tendon sheaths, or soft tissues for longer-duration local effects with less systemic side effects

Back 10

intraarticular corticosteroids

i.e. triamcinolone acetonide
depo-methylprednisolone

Front 11

What is used often in RA when one or tow joints remain active or initially if severely affected as well as to control acute gout, tendinitis or bursitis, or other localized rheumatic conditions

Back 11

intraarticular corticosteroids

Front 12

Methotrexate inhibits synthesis of what and is an antagonist to what?

Back 12

inhibits purine & pyrimidine synthesis

folate antagonist

Front 13

In rheumatic disease, is methotrexate more anti-inflammatory or immunosuppressive?

Back 13

anti-inflammatory

Front 14

What does methotrexate increase that helps decrease inflammation?

Back 14

increases adenosine

Front 15

Methotrexate is FDA approved for what 3 rheumatic conditions?

Back 15

RA
Juvenile idiopathic arthritis
Psoriasis

Front 16

Methotrexate is not FDA approved for Wegener's granulomatosis, spondyloarthropathies, and what 2 other diseases?

Back 16

SLE
Polymyositis/dermatomyositis

Front 17

How can you decrease the absorption variable of methotrexate?

Back 17

by food or raising the dose

Front 18

True or False

Methotrexate widely distributes to tissues

Back 18

True

Front 19

Methotrexate is converted to MTX polyglutamates in what?

Back 19

RBC

Accumulation T1/2 2-45 weeks
Elimination T1/2 1-4 weeks

Front 20

True or False

Genetic variation in enzymes is involved in MTX handling

Back 20

True

Front 21

Methotrexate is primarily eliminated by what?

Back 21

kidneys (bile)

Plasma half-life 3-10 hours
Dose is often reduced with mild renal impairment, or not used if more severe

Front 22

Methotrexate is retained in the __________ several weeks, and in the ___________ several months

Back 22

kidney = weeks
liver = months

Front 23

Methotrexate's onset of effect is ______ weeks and maximum effect is _______ months.

Back 23

3-6 weeks
3-6 months

*disease may flare within 1 month of discontinuation and may be disease-modifying

Front 24

What is the most common side effect of methotrexate?

Back 24

GI

Others include stomatitis, hematologic, alopeica, CNS "blah" effects

Front 25

What is the main concern with methotrexate use?

Back 25

hepatotoxicity

fibrosis and cirrhosis may occur

Front 26

An increase in levels of what often occurs with methotrexate and may requre reduction of dosage to prevent more serious long-term toxicity

Back 26

transaminase levels

Front 27

Hepatotoxicity (with methotrexate) may correlate with what?

Back 27

hypoalbuminemia

Front 28

What kind of dosing reduces the risk of hepatotoxicity in methotrexate users?

Back 28

weekly dosing

Front 29

What kinds of pulmonary toxicities might occur with methotrexate users?

Back 29

acute hypersensitivity pneumonitis vs. toxic drug reaction

Front 30

malignancy
myelosuppression
rash
nodulosis of skin and viscera
fetal abnormalities
oligospermia
increased risk of infection
nephrotoxicity at high doses are all associated with what drug?

Back 30

methotrexate

Front 31

What can you take to decrease methotrexate toxicities? (esp. stomatitis, liver toxicity, hematologic)

Back 31

folic acid (does not seem to reduce efficacy)

*folinic acid can reduce efficacy

Front 32

What are the contraindications for methotrexate?

Back 32

acute or chronic liver disease
excessive alcohol consumption
pregnancy
active infection
severe anemia or leukopenia
unreliable patient

Front 33

You should take precautions with methotrexate in what kind of patients?

Back 33

w/ abnormal renal function
obesity, diabetes (increased risk of liver toxicity)
preexisting lung disease
elderly-decrease dose

Front 34

What drugs interact w/ methotrexate to lower renal clearance?

Back 34

probenecid
salicylates
NSAIDs
Diuretics

Front 35

What drugs interact w/ methotrexate to displace binding sites?

Back 35

alicylate
sulfonamids
phenytoin

Front 36

How is oral dosing done w/ methotrexate?

Back 36

once per week

7.5-25 mg/week

Front 37

When is subcutaneous methotrexate used?

Back 37

when concerns of bioavailability with higher oral doses

can also given intramuscular and IV

Front 38

what common additive may decrease the efficacy of methotrexate?

Back 38

caffeine

Front 39

Along with an annual chest x-ray, what labs are also monitored with methotrexate?

Back 39

CBC
Liver enzymes, albumin (reduce need for liver biopsy)
Creatinine

checked monthly then reduced if well tolerated

Front 40

What is the anchor for most combination therapies?

Back 40

methotrexate

Front 41

What is used to lower antibody formation to biologics?

Back 41

methotrexate

Front 42

The colon splits Sulfasalazine into 5-ASA (aminosalicylic acid_ & sulfapyridine (SP). Which one is well absorbed and metabolized by acetylation?

Back 42

SP

5-ASA is poorly absorbed and eliminated in feces

Front 43

Sulfasalazine is not FDA approved for ankylosing spondylitis and psoriatic arthritis but is FDA approved for what? (2)

Back 43

rheumatoid arthritis
juvenile idiopathic arthritis

Front 44

Although suflasalazine has some benefit for rheumatologic disease, what product is the active moiety?

Back 44

sulfapyridine (SP)

approx. time to benefit: 1-3 months

Front 45

Sulfasalazine's toxicity dropout rate is _______%.

It's side effects include:

Back 45

20-30%

dizziness, headache, GI (nausea), rash, photosensitivity

Front 46

What is the greatest concern regarding sulfasalazine's toxicity?

Back 46

hematologic toxicity

-leukopenia
megaloblastic, hemolytic, aplastic anemias
-thrombocytopenia

Front 47

What labs do you monitor when using sulfasalazine?

Back 47

G6PD
CBC
Liver enzymes
Periodic urinanalysis & renal function tests

Front 48

Leflunomide is a _________ inhibitor

Back 48

pyrimidine synthesis inhibitor which decreases inflammation

Front 49

Leflunomide is FDA approved for what? (1)

Back 49

rheumatoid arthritis

Front 50

Leflunomide PK:

aborption: tablet ___% (vs. solution)
>____% bound to albumin

Back 50

80%

>99.3% bound

Front 51

Leflunomide is a prodrug whose active metabolite inhibits what?

Back 51

active metabolite inhibits CYP2C9

Front 52

Leflunomide is eliminated in:

Back 52

metabolism
kidneys
bile

**NOT DIALYZABLE***

Front 53

What is the half-life of leflunomide?

Back 53

15-18 days

(detectable at 2 years-enterohepatic circulation)

Front 54

What is the approx. time to benefit w/ lefulnomide?

Back 54

4-12 weeks

Front 55

Leflunomide is sometimes used w/ methotrexate in what?

Back 55

RA

appears to improve efficacy but higher frequency of liver toxicity

Front 56

These toxicities relate to what drug?
increased liver enzymes
diarrhea
rash
teratogenicity
alopecia
headach
infection
bone marrow suppression
intersitial lung disease

Back 56

leflunomide

Front 57

Leflunomide is contraindicated in?

Back 57

pregnancy

prior to pregnancy, drug is eliminated w/ cholestryramine

Front 58

This drug is an antimalarial and anti inflammatory FDA approved for RA and SLE

Back 58

hydroxychloroquine (Plaquenil)

Front 59

Hydroxychloroquine has a half life of ________
Eliminated in the _________
and approx time to benefit is _______

Back 59

half life= 1-2 months

eliminated mainly in kidney, also liver

time to benefit: 2-6 months

Front 60

Hydroxychloroquine is commonly used in Lupus in lupus-related arthritis, to reduce frequency of flare, but most useful for ______?

Back 60

cutaneous disease symptoms of SLE

Front 61

Although this drug is weaker, slower, but has less toxicity, it is commonly used in combo. w/ methotrexate and suflasalazine for what ?

Back 61

hydroxychloroquin

RA

Front 62

What is the most serious concern when using hydroxychloroquine?

what are some other side effects?

Back 62

Retinal damage

others: GI, insomnia, myopathy, leukipenia

Front 63

What tests should you monitor when using hydroxychloroquine?

Back 63

opthalmologic exam

CBC
LFTs
Creatinine

Front 64

strong immunosuppressive drug with high toxicity used in many of the systemic autoimmunce rheumatic disease for serious manifestations (though not FDA approved for these)

Back 64

cyclophosphamide

SLE, Wegener's granulomatosis, microscopic polyangitis, polyarteritis nodosa, systemic necrotizing vasculitis ILD w/ connective tissue disease

Front 65

The monthly pulse intravenous regimen of Cyclophosphamide is often used for what?

Back 65

SLE

.5-1 g/m^2 IV per month

Front 66

The daily oral 1-2 mg/kg/day dose of cyclophophamide tends to be more toxic than monthly IV so it is used for initial treatment and this disease:

Back 66

vasculitis

Front 67

Due to the toxic metabolite, acrolein, from this drug, bladder toxicity is a significant concern including hemorrhagic cystitis and bladder cancer

Back 67

cyclophophamide

Front 68

How can you minimize bladder toxicity with cyclophosphomide?

Back 68

hydration
monthly IV instead of daily oral
Mesna to reduce hemorrhagic cystitis

Front 69

Other than bladder complications, what are some other toxicities from cyclophosphamide?

Back 69

hematopoietic suppression
immunosuppression
opportunistic infection
myeloproliferative disorders
sterility
teratogenesis
SIADH

Front 70

What is used for nausea and vomiting when taking cyclophosphamide?

Back 70

ondansetron + dexamethasone

Front 71

What immunosuppressive drug is metabolized by TPMT to mercaptopurine?

Back 71

Azathiprine

high risk of toxicity if genetically low or absent TPMT (thiopurine methyltransferase)

Front 72

As with most toxicities, Azathiprine has GI upset, leukopenia, thrombocytopenia, risk of infection, and risk of this cancer:

It also has a pregnancy category of:

Back 72

lymphoma

D

Front 73

Although the onset of effects of Azathioprine is ______ weeks, it's peak is at ____ months, which is why you need ____ months at final dose before concluding it is ineffective

Back 73

6-12 weeks
peak is 6 months
3-6 months

Front 74

Azathiprine is FDA approved for: (1) but is still commonly used in (2) even though FDA approved

Back 74

RA
SLE and PM/DM

Front 75

What is measured before starting treatment with Azathioprine?

What other things are monitored during treatment?

Back 75

TPMT enzyme activity

CBC, liver function tests, chemistry panel

Front 76

Which drug inhibits purine nucleotide synthesis (inhibits IMPDH)?

Back 76

Mycophenolate mofetil

Front 77

Mycophenolate mofetil suprresses:
proliferation of _________
Formation of _________
___________ of adhesion molecules
___________ of inflammatory cells

Back 77

proliferation of B & T cells
formation of antibodies
Glycosylation of adhesion molecules
Migration of inflammatory cells

Front 78

Mycophenolate mofetil is often used in lupus, especially lupus _________

Back 78

nephritis

has been used for other rheumatic diseases

Front 79

True or False

Gold was an early DMARD but now rarely used due to inconsistent benefit, delayed onset, and toxicity

Back 79

True

Front 80

What must you screen for before using a biologic?

Back 80

TB and hepatitis

latent TB before anti-TNF agents

Front 81

True or False

It is okay to combine biologics

Back 81

False

Front 82

True or False

It is good to use live vaccines with biologics to increase treatment efficacy

Back 82

False

Front 83

What pro-inflammatory cytokines are prevalent in RA? (4)

Back 83

TNF-alpha
IL-1
IL-6
IL-8

Front 84

What anti-inflammatory cytokines are lacking in RA? (6)

Back 84

IL-1ra
sIL-1R
sTNFR
IL-10
IL-4
IL-11

Front 85

What biologic is a soluble TNF receptor?

Back 85

Etanercept

Front 86

What are the monoclonal antibodies for TNF?

Back 86

Infliximab
Adalimumab
Golimumab
Certolibumab Pegol

Front 87

The effects of TNF-a are better when combined with what non-biologic?

Back 87

methotrexate

Front 88

TNF-alpha inhibitors were first used for RA but were later found effective in what? (2)

Back 88

ankylosing spondylitis (esp. axial pain)
psoriatic arthritis

Front 89

What are the 3 major concerns when using TNF-a inhibitors?

Back 89

increased infection (TB, hep B)
malignancies
demyelinating disorder exacerbation

Front 90

Which foods should you avoid if taking a TNF-a inhibitor?

Back 90

those foods w/ increased Listeria risk

Front 91

True or False

It takes at least a few weeks for TNF-a inhibitors to work

Back 91

False

Rapid onset: days-weeks

Front 92

True or False:

Patients who do not respond to one, or who lose responsiveness to a TNF-alpha inhibitor will NOT respond to another anti-TNF

Back 92

False

Front 93

What disease might make one anti-TNF better to use than another anti-TNF?

Back 93

inflammatory bowel disease

Front 94

All anti-TNF-a are given subcutaneously except this one, which is given IV

Back 94

Infliximab = IV

Front 95

Etanercept (binds TNF) is FDA approved for these 3 arthritis and ankylosing spondylitis

Back 95

RA
juvenile idopathic arthritis
psoriatic arthritis

Front 96

Infliximab is a chimeric IgG1 monoclonal Ab that binds TNFa, but patients may develop their own antibody to the drug. What can lower this possibility?

Back 96

give methotrexate with Infliximab

FDA approved for RA when given with methotrexate

Front 97

Infliximab might cause infusion and hypersensitivity reactions, and can also cause this autoimmune disorder

Back 97

drug induced lupus

Front 98

Adalimumab and Golimumab are both human IgG1 monoclonal Ab that are FDA approved for RA, psoriatic arthritis, and ankylosing spondylits, but only one is also approved for juvenile idopathic arthritis:

Back 98

Adalimumab

Front 99

This drug is a pegylated Fab fragment of humanized anti-TNF antibody that lackss an Fc portion and FDA approved for RA:

Back 99

Certolizumab Pegol

Front 100

This drug is an recombinant IL-1Ra that inhibits inflammatory and immunoligical responses and is FDA approved for RA

Back 100

Anakinra

Less often used in adult RA

Front 101

Rituximab is a chimeric monoclonal antibody directed against the B cell surface antigen ____

Back 101

CD20

Front 102

Rituximab depletes B cells that contribute to inflammation which causes depletion in:
___________ formation
___________production
___________activation

Back 102

Authantibody formation
cytokine production
T-cell activation

Front 103

Rituximab (with methotrexate) is FDA approved for what?

What are it's unapproved uses?

Back 103

RA unresponsive to TNF-a inhibitor

SLE, Wegener's granulomatosis, DM

Front 104

What can you do to limit injection reactions with Rituximab?

Back 104

Premedicate w/ IV steroids
Tapering dose of oral steroids days 1-16
Consider acetaminophen/antihistamine
hold antihypertensives if possible

Front 105

What is the duration of benefit for Rituximab?

Can it be re-dosed if loss of benefit?

Back 105

variable, usually >6 months

yes

Front 106

This biologics is a selective costimulation modulator that inhibits T-lymphocyte activation

Back 106

Abatacepts

Front 107

Abatacept is FDA approved for what? (2)

Back 107

RA
juvenile idiopathic arthritis

Front 108

Abatacept toxicities include serious infections, infusion-related reactions, and exacerbations of this:

Back 108

COPD

Front 109

What should you avoid when giving the IV infusion of Abatacept over 30 min (repeat 2 & 4 week after initial then every 4 week)

Back 109

silicone syringes

Front 110

What is Tocilizumab? and what is it FDA approved for?

Back 110

humanized IL-6R inhibiting antibody

RA unresponsive to TNF-a inhibitor

Front 111

What are the 3 Serious Toxicities noted for Tocilizumab?

Back 111

infections
GI perforation
Hypersensitivity rxns (anaphylaxis)

other toxicities are: URIs, nasopharyngitis, HA, hypertension, raised liver enzymes & lipids, and lowered neutrophils & plateles

Front 112

This investigational biologic inhibits soluble human B-lymphocyte stimulator (BLyS) and shows promise for the treatment of lupus

Back 112

Belimumab