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Block 7 Week 5 > Corticosteroids and DMARDs > Flashcards

Corticosteroids and DMARDs Flashcards

1
Q

RA is a progressive, systemic, inflammatory disorder characterized by (Blank) synovitis, joint erosions and multisystem (Blank) articular manifestations.

A

symmetrical

extra-articular

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2
Q

(blank) is at the root of all problems in RA, including joint pain, swelling and stiffness.

A

Inflammation

-> therefore controlling inflammation is key

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3
Q

What are the 2 categories that mdications fall into for treatment of RA?

A
  • drugs that treat pain and inflammation but do not limit joint damage
  • drugs that help control disease and limit joint damage
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4
Q

What drugs are used to treat pain and inflammation but do not limit joint damage?

A

corticosteroids (glucorticosteroids), NSAIDS and other analgesics

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5
Q

What drugs hep control disease and limit joint damage?

A

DMARDS (disease modifying anti-rheumatic drugs) and

Biologics

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6
Q

Rheumatologists tend to use (blank) and (Blank) as the first tratment in RA therapy, with (blank X 2) playing supportive roles and controlling acute inflammation

A

DMARDS
Biologics

Steroids, NSAIDs

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7
Q

(blank) and their biologically active synthetic derivatives (prednisone, dexamethasone, prednisolone) potently suppress inflammation and their usefulness in a variety of inflammatory and autoimmune disease making them among the most frequently prescribed drugs.

A

Corticosteroids (glucocorticoids)

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8
Q

Why are corticosteroids (glucocorticoids) dangerous?

A

because they exert effects on almost every organ system, the clincal use and withdrawal from corticosteroids are complicated by many serious or life-threatening side effects

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9
Q

Disease-modifying anti-rheumatic drugs (DMARDs) are a category of unrelated drugs defined by their use in (blank)

A

RA

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10
Q

DMARDs are either (blank) or (Blank)

A

antimetabolites

TNF alpha blockers

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11
Q

Steroids blunt the immune system but are insufficient to do what?

A

slow the progression of the disease

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12
Q

NSAIDs treat inflammation but not the (blank)

A

underlying disease

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13
Q

DMARDs can do what to the progression of the disease (RA)?

A

slow down or stop progression of joint damage

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14
Q

Are the side effects of all DMARDs the same?

A

no

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15
Q

(blank) for RA are drugs targeting specific parts of the immune system to inhibit inflammation.

A

Biologics

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16
Q

What do Biologics do?

A

reduce joint pain and swelling and control symptoms and disease activity of moderate to severe RA when DMARDs fail.

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17
Q

Whats pretty cool about using biologics long term?

A

they can slow down joint damage and improve joint use and movement

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18
Q

What are these signs of:

  • recurrent hyperuricemia
  • arthritis
  • severe pain
A

Gout

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19
Q

What is gout caused by?

A

by deposition of uric acid crystals in the joint space as a result of long-standing hyperuricemia (increased production or decreased excretion of uric acid), causing an inflammatory reaction

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20
Q

What does an acute attack of gout present as?

A

severe joint pain most often in distal phalangeal joints

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21
Q

What is the inflammatory response to gout like?

A

local infiltration of granulocytes-> which phagocytize the urate crystals

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22
Q

(blank) production is high in synovial tissues and in the leukocytes associated with the inflammatory process.

A

lactate

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23
Q

Since lactate production is high in synovial fluid and in the leukocytes associated with the inflammatory process, what does this mean for the pathology of gout?

A

that the pH will drop which facilitates the deposition of uric acid

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24
Q

Urate is also deposited in interstitial tissues of the (blank) and accumulates as (Blank)

A

kidney

kidney stones

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25
Q

What is the solubility in serum of uric acid?

A

7 mg/dl

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26
Q

Levels of urate are (blank) in children and are elevated in (blank) after puberty

A

3-4

boys

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27
Q

Levels of urate are (lower/higher) in women but (Fall/Rise) after menopause

A

lower

rise

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28
Q

Gout is more prevalent in (Blank) 95% of cases with peak incidence in the (blank) decade

A

male

5th

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29
Q

Gout is prositively correlated with …..?

A

short, fat, diabetic alcoholicl males who live in warm places and are poor and stupid

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30
Q

How do we get urate from AMP?

A

AMP-> IMP-> hypoxanthine-> xanthine-> uric acid (keto) -> uric acid (enol)-> urate

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31
Q

Adenosine deaminase deficiency is associated with (blank)

A

SCID

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32
Q

What causes primary gout?

A

loss of hypoxanthine-guanine phosphoribosyl transferase deficiency (x-linked, Lesch-Nyhan)

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33
Q

What are the normal uric acid levels in females?

Males?

A
  1. 4-6.0 mg/dL

3. 4-7 mg/dL

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34
Q

What causes secondary gout?

A
  • Overproduction of urate secondary to increased breakdown of blood cells as in leukemia
  • Chemotherapy
  • decreased excretion of urate due to use of alcohol, thiazide diuretics or low doses of aspirin
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35
Q

You can get asymptomatic hyperuricemia, patients with serum urate above (blank) are at risk of devloping out.

A

7 mg/dl

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36
Q

What is this:
exquisitely painful monoarticular arthritis which presents most commonly in 1st metatarsal joint with 90% of untreated patients having involvement of the great toe.

A

acute gout

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37
Q

What is this:

following the initial attack of gout, a remission of indeterminate length

A

Intercritical period

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38
Q

What is this:

frank gouty arthrtis with xtals in the synovium and some degree of erosion of bone.

A

Chronic tophaceous gout

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39
Q

What is this:

Uric acid kidney stones occur in 20% of patients with gout

A

Nephrolithiasis

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40
Q

Chronic gout leads to deposition of urates into a chalky mass known as a (blank)

A

tophus.

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41
Q

Where are you most likely to find tophi?

A

in soft tissues, including tendons and ligaments, around joints

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42
Q

Tophaceous gout results from continued precipitation of (blank) during attacks of acute gout

A

sodium urate crystals

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43
Q

How do you know you have gout

A

befringement shows urate crystals-> needle like

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44
Q

If you see rhomboid shape crystal what is it ?

A

calcium pyrophosphate-> pseudo gout

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45
Q

Who do you typically see pseudogout in and what is the disease progression?

A

over age of 50-> can lead to acute, subacute, chronic arthritis of knees, wrists, elbows, shoulders, and ankles. THe articular damage is progressive, though in most persons not severe

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46
Q

What drug is used ONLY for gouty arthritis?

A

Colchicine-> it is an antiinflammatory agent, and a prophylactic agent

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47
Q

What is the drug of choice for acute atacks of gouty arthritis?
How long does it take to work?

A

Colchicine

12-24 hours after oral admin

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48
Q

T or F

Cochicine does NOT influence the renal excretion of uric acid or its concentration in blood

A

T

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49
Q

How does colchicine work?

A

binds to tubulin and interferes with the function of mitotic spindles/,microtubules of granulocytes-> granulocytes cant get into the inflamed area

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50
Q

Since Colchicine prevents granulocytes from entering inflamed area then you reduce the amount of (Blank) and thus reduce inflammation

A

lactic acid

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51
Q

Neutrophils exposed to urate crystals, do what with them?

A

ingest them and produce a glycoprotein which may be causative agent of acute gouty arthritis

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52
Q

This glycoprotein substance that neutrophils produce when ingesting urate crystals is thought to be the causative agent of acute gouty arthritis , what drug is thought to prevent the metabolizm of granulocytes and thus decrease this glycoprotein and relieve arthritic gouty symptoms?

A

colchicine

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53
Q

(blank) inhibits the release of histamine-containing granules from mast cells

A

Colchicine

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54
Q

Large amounts of colchicine enter the (blank) tract… how?

A

intestinal

bile and intestinal secretions

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55
Q

Since colchicine is predominantly in the intestine, where does poisioning show its manifestations?

A

GI tract :)

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56
Q

The kidney, liver, and spleen also contain high concentrations of colchicine, but it is apparently largely excluded from (blank, blank and blank)

A

heart, skeletal muscle, brain

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57
Q

Colchicine is metabolized to a mixture of compounds by (blank). THe majority of the drug is excreted in (Blank) but 10-20% is excreted in the (blank)

A

CYP3A
Feces
Urine

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58
Q

IF you have a patient with liver disease, what will happen to the excretion of colchicine?

A

that hepatic uptake and elimination are reduced and a greater fraction will now be excreted in urine

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59
Q

What are the adverse effects of colchicine?

A

Orally-> nausea, vomiting, abdominal pain, and diarrhea

IV-> sloughing skin and subcutaneous tissue

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60
Q

What are the benefits of giving colchicine via IV?

A

reduces risk of GI distubrances and provides faster relief (6-12 hrs)

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61
Q

If you give very high doses of colchicine what may this result in?

A

liver damage and blood dyscrasias

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62
Q

How do uricosuric agents work?

A

they treat gout by increase the excretion of uric acid by blockings its reabsorption for the urine

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63
Q

What are three uricosuric agents?

A

probenecid
sulfinpyrazone
benzbromarone

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64
Q

What is this:

anti-inflammatory NSAID and uricosuric

A

sulfinpyrazone

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65
Q

What is this:

a uricosuric that is potent, effective and dosed once daily

A

Benzbromarone

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66
Q

What is this:
organic acids
-reduce urate levels by acting on the anionic transport site in the rental tubule to prevent reabsorption of uric acid

A

Probenecid (benemid) and sulfinpyrazone (anturane)

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67
Q

(blank) and (Blank) undergo rapid oral absorption and should be used with (blank)

A

Probenecid (benemid) and sulfinpyrazone (anturane)

Colchicine

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68
Q

Probenecid and sulfinpyrazone inhibit the excretion of other drugs that are actively secreted by renal tubules, including (blank X 4)

A

penicillin, NSAIDs, cephalosporins, and methotrexate

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69
Q

Increased urinary concentration of uric acid may result in the formation of (blank).

A

Urate stones (urolithiasis)

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70
Q

How can you decrease the risk of urate stones?

A

ingestion of large volumes of liquid and potassium citate (alkalize urine)

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71
Q

What are common adverse effects of probenecid and sulfinpyrazone?

A

GI disturbances and dermatitis

-rarely blood dyscrasias

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72
Q

(blank) inhibit the synthesis of uric acid by inhibiting the xanthine oxidase, an enzyme that converts hypoxanthine to xanthine and xanthine to uric acid, the terminal steps in uric acid biosynthesis

A

Allopurinol

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73
Q

Allopurinol is metabolized by xanthine oxidase to (blank), which also inhibits xanthine oxidase.

A

alloxanthine

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74
Q

Allopurinal also inhibits de novo (blank) synthesis

A

purine

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75
Q

Allopurinol represents a (blank) approach to therapy

A

rational

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76
Q

Allopurinal commonly produces (blank) disturbances and (blank)

A

GI

dermatitis

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77
Q

Allopurinal rarely produces these side effects:?

A

hypersensitivity, including fever, hepatic dysfunction and blood dyscrasias

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78
Q

Allopurinol should be used with caution in patients with (blank) or (blank)

A

liver disease or bone marrow depression

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79
Q

Allopurinol blocks the action of xanthine oxidase by (blank) and is also metaobilized by it to form alloxanthine which also inhibits xanthine oxidase

A

substrate competition

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80
Q

What are the three FDA approved NSAIDs used in gout?

A

indomethacin, naproxen, sulindac

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81
Q

What are the benefits of using NSAIDs in gout?

A

faster onset of relief (compared with colchicine)

  • w.in 2-4 hous for indomethacin
  • less toxic; better tolerated
  • widespread use and familiarity
  • cost
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82
Q

(blank) such as prednisone, prednisolone, and triamcinolone have been used to relieve gout.

A

corticosteroids

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83
Q

T or F

steroids may have less utility in acute gout because they do not work as well as NSAIDs or colchicine

A

T

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84
Q

T or F
corticosteroids are the “last resort” therapy, used in patients that cannot take or do not benefit from NSAIDs or colchicine

A

T

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85
Q

What is febuxostat (Uloric)?

A

used to treat gout by lowering uric acid levels

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86
Q

How does febuxostate (uloric) lower uric acid levels and is it effective?

A

non-purine inhibitor- forms a complex with the enzyme resulting in inhibition
-lowers it even better allopurinol

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87
Q

How do you metabolize and eliminate febuxostate (uloric)?

A

CYP2C9

-renal and hepatic elimination

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88
Q

In whom do you use febuxostate (uloric)?

A

used for patients with attacks, not asymptomatic patients. Can and is combined wiht NSAIDs or Colchicine

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89
Q

What are the SEs of febuxostat (uloric)?

A

LIver toxicity and potential CV SE are of concern and being evaluated in phase IV

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90
Q

(blank) is indicated for use in the pediatric population for management of elevated uric acid in patients receiving chemotherapy for leukemia, lymphoma, or solid tumors and are anticipated to develop tumor lysis syndrome.

A

Rasburicase (Elitek)

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91
Q

(blank) occurs in malignancies that are highly proliferative and have high tumor burdens, such as lymphomas and leukemias.

A

Tumor lysis syndrome

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92
Q

What metabolic abnormalities usually accompany tumor lysis syndrome?

A

hyperphosphatemia, hyperkalemia, hyperuricemia, hypocalcemia and renal dysfunction

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93
Q

(blank) is a hallmark finding of tumor lysis syndrome

A

Hyperuricemia (uric acid level greater or equal to 8 mg/dL)

94
Q

Which has more SEs, rasburicase (for children with cancer) or allopurinol?

A

rasburicase

95
Q

Which is more expensive, Rasburicase or Allopurinol?

A

RASBURICASE By a lot!!!

96
Q

Acute gout is treated with (blank) .

A

Nonsalicylate NSAIDs (indomethacin, naproxen, and sulindac)

97
Q

Acute gout is treated with Nonsalicylate NSAIDs (indomethacin, naproxen, and sulindac). These NSAIDs are preferred to colchicine because of the (blank) associated with the use of colchicine.

A

diarrhea

98
Q

Chronic gout is treated with (blank) to increase the elimination of uric acid and (blank) to inhibit uric acid production

A 
uricosuric agents (probenecid, sulfinpyrazone)
Allopurinol
99
Q

What are maitenance drugs for gout?

A

allopurinol (zyloprim), probenecid (benemid) and sulfinpyrazone (anturane)

100
Q

(blank) is needed for several weeks to prevent acute attacks while serum uric acid levels are being lowered

A

Colchicine

101
Q

What besides meds to you need to give to prevent renal calculi in gout?

A

High fluid intake and alkaline urine

102
Q

What are the corticosteroids used in RA?

A

predinisone, predinisolone, dexamethasone

103
Q

What are the DMARDS; anti-TNF alpha drugs?

A

adalimumab, infliximab, etanercept, anakinra

104
Q

What are the DMARDs: antimetabolites?

A

Azathioprine, Methotrexate, cyclophosphamide, cyclosporine

105
Q

(blank) is a chronic, progressive, systemic, autoimmune disease

A

Rheumatoid arthritis (RA)

106
Q

What besides joint problems will you get with RA?

A

pulmonary and vascular involvement, peripheral neuropathy, keratoconjunctivitis

107
Q

What is the most common systemic inflammatory disease and what age is it most common in?

A

RA-> 30-60 in women (later in life for men) 3X times more likely in women.

108
Q

40 to 60% of patients with advanced RA will survive (blank) years or less following diagnosis and die (blank) years earlier than expecte.

A

5 years or less

10-15 years

109
Q

What are the goals of RA therapy?

A

control inflammation

  • alleviate pain
  • slow progression/rate of joint damage
  • reduce disease activity and induce remission
  • maintain function for essential daily activities
  • max quality of life
110
Q

What are the ways you can do combo therapy for RA therapy?

A

several DMARDs
DMARDS oral and biological
DMARDs and corticosteroids

111
Q

What do corticosteroids target?

A

phospholipase A2

112
Q

What do NSAIDs target?

A

COX

113
Q

What do 5 LOX inhibitos Sulfasalazine, leukotriene receptor antagonist (Zafirulukast, zileuton) inhibit?

A

LOX

114
Q

What do you want to inhibit LOX?

A

cuz it creates HETEs, leukotrienes, lipoxins which will mobilize phagocytes, change vascular permeability and cause inflammation

115
Q

What does COX do?

A

creates prostanoids (prostaglandins, prostacyclin, thromboxane)-> creates inflammation

116
Q

What does COX-1 do?

A

prostaglandins associated with:
GI mucosal integrity
Platelet function
Renal function

117
Q

What does COX-2 do?

A

Prostaglandins associated with:
Inflammation
Pain
Fever

118
Q

What are the pros of NSAID therapy?

A

Effective (±) control of inflammation and pain
Effective reduction in swelling
Improves mobility, flexibility, range of motion
Improve quality of life
Low-cost

119
Q

What are the cons of NSAID therapy?

A

Does not affect disease progression
GI toxicity common
Renal complications (eg, irreversible renal insufficiency, papillary necrosis may occur)
Hepatic dysfunction
CNS toxicity with high dose (salicylates)

120
Q

What is this:
involved in a wide range of physiological processes, includingstress response, immune response, and regulation of inflammation, carbohydrate metabolism, proteincatabolism, bloodelectrolytelevels, and behavior. There are 2 types, glucocorticoids and mineralcorticoids

A

Corticosteroids

121
Q

What is this:
control carbs, fat and protein metabolism, and are anti-inflammatory by preventing phospholipid release, decreasing eosinophil action and a number of other mechanisms.

A

Glucocorticoids

122
Q

(Blank) control electrolyte and water levels, mainly by promoting sodium retention in the kidney.

A

Mineralcorticoids

123
Q

(blank) are physiological modulators of the immune system and protect the organism against life-threatening consequences of a full-blown inflammatory response.

A

Glucocorticoids

124
Q

(blank) profoundly inhibit the immune system at multiple sites.

A

Corticosteroids

125
Q

Corticosteroids regulate gene transcription, inhibit expression of (blank), (blank), (blank), and (blank)

A

IFN-gamma
Interleukins
TNF-alpha
GM-CSF (granulocyte-macrophage colony-stimulating factor)

126
Q

Corticosteroids will increase circulating levels of (blank) by interfering with adhesion and decrease (Blank X 3)

A

neutrophils

Eosinophils, lymphocytes, and monocytes

127
Q

The (blank and blank) are capable of bidirectional interactions in response to stress, and these interactions appear to be important for homeostasis

A

HPA axis and the immune system

128
Q

Corticosteroids enter target cells by (blank) and bind to cytosoic receptors which are transcription factors, The steroid receptor complex translocates into the (blank),

A

simple diffusion

nucleus

129
Q

Corticosteroids inhibit (blank) production

A

Eicosanoid production

130
Q

Corticosteroids (glucocorticoids) inhibit (blank) which inhibits phospholipase A2 which inhibits COX-2 expression

A

Lipocortin

131
Q

What are the 2 glucocorticoids of note?

A

prednisone

dexamethasone

132
Q

The corticosteroids prednisone and dexamethasone prevent (Blank) and (blank) activation

A

leukocyte and endothelial cell activation

133
Q

Corticosteroids block the synthesis of cytokines, how so?

A

binds to response element of cytokine gene and inhibits transcription

  • binds to other stimulatory factors
  • accelerates degredation of mRNA coding for cytokine
134
Q

Corticosteroids block the action of cytokines, how so?

A
  • inhibits transcription of “transcription factors” induced by cytokines
  • blocks the action of cytokine-induced transcription factors
  • blocks the synthesis of cytokine receptors
135
Q

Corticosteroids block the effects on inflammatory mediators, how so?

A
  • increases lipocortin (inhibits PLA2)
  • decreases prodction of enzymes inolved in creating inflammatory mediators
  • decreased expression of adhesion molecules
  • increased expression of genes coding for enzymes that degrade inflammatory mediators
136
Q

How do you give prednisone?

A

orally

137
Q

How do you give dexamethasone?

A

oral, injectable, topical

138
Q

Compared to the endogenous corticosteroids, the synthetic ones have stronger (blank), lower (blank), Longer (blank)

A

potency
dose
duration

139
Q

Corticosteroids are well absorbed (blank)

A

orally

140
Q

Corticosteroids are highly bound to (blank)

A

plasma proteins-CSBG

141
Q

How are corticosteroids metabolized and excreted?

A

metabolized by liver an excreted by kidney

142
Q

Is there a lag time before onset of action for steroids?

A

yes!

143
Q

THe plasma half life of corticosteroids is (longer/shorter) than biological halflife

A

shorter

144
Q

T or F

there is a persistence of effect after disappearnce from plasma

A

T

145
Q

What are the adverse effects of Chronic use of glucocorticoids?

A
  • adrenocortical insufficiency: suppression of HPA
  • Cushings syndome (buffalo hump, moon face)
  • DM
  • CNS effects
  • impaired wound healing
  • MSK effects (osteoporosis, muscle weakness, atrophy)
  • CV effects (fluid retention, edema, HTN)
  • gastric ulcer
  • increased suscpetibility to infection
  • growth inhibition in children
146
Q

What are the pros of corticosteroid therapy in RA?

A

Anti-inflammatory and immunosuppressive effects
Can be used to bridge gap between initiation of DMARD therapy and onset of action
Intra-articluar injections can be used for individual joint flares and this is the major benefit in rheumatic arthritis

147
Q

What are the cons of corticosteroid therpay in RA?

A

Does not conclusively affect disease progression
Tapering and discontinuation of use often unsuccessful
Low doses result in skin thinning, ecchymoses, and Cushingoid appearance
Significant cause of steroid-induced osteopenia

148
Q

(blank) blunt the immune response but are insufficient to slow down the progression of the disease

A

Steroids,

149
Q

(blank) treat the inflammation symptoms but no the underlying cause

A

NSAIDs

150
Q

(blank) retard or halt the underlying progression, limiting the amount of joint damage that occurs in RA while lacking the anti-inflammatory and analgesic effects observed with NSAIDs; having an effect on RA with more delayed onset than either NSAIDs or corticosteroids.

A

DMARDs

151
Q

Do DMARDs have a delayed onset?

A

yes D for Delayed

152
Q

DMARDs come in 2 categories?

A

oral or biologic drugs

153
Q

(blank) DMARDs are small-molecule chemical drugs. The mechanism of action of each of these drugs is not well defined or unknown in some cases.

A

Oral

154
Q

(blank) DMARDs are genetically engineered antibodies and proteins.

A

Biologic DMARDs

155
Q

What are the most typical members of the biologic DMARDs drug class?

A

Tumor necrosis factor-alpha (TNFalpha) blockers

-other targets are IL-1 and IL-6 AND CD20 and CD28

156
Q

Biologic DMARDs block the activity of (blank) and other cell-signaling molecules

A

immunostimulatory cytokines

157
Q

WHen do use DMARDs?

A

Established persistent disease (chronic synovitis), development of erosions or joint space narrowing on radiographs

158
Q

Should you wait for radiographic changes to give DMARDs?

A

No

159
Q

Are DMARDs fast or slow acting? How long does it take to work?

A

slow acting, taking greater than 3 months for measurable clinical benefits to be observe

160
Q

What DMARD is a purine synthesis inhibitor?

A

Azathioprine

161
Q

What DMARD is a calcineurin inhibitor?

A

Ciclosporin (cyclosporin A)

162
Q

What DMARD is a pyrimidine synthesis inhibitor?

A

Leflunomide

163
Q

What DMARD is a purine metabolism inhibitor?

A

Methotrexate (MTX)

164
Q

What DMARD is a T-cell costimulatory signal inhibitor?

A

Abatacept

165
Q

What DMARDs are a TNF alpha inhibitor?

A

Adalimumab
Etanercept
Golimumab
Infliximab

166
Q

What DMARD suppress IL-1 and TNF-alpha, induces apoptosis of inflammatory cells and decreases chemotaxis

A

Chloroquine and hydroxychloroquine

167
Q

What DMARD reduces numer of T lymphocytes?

A

D-penicillamine

168
Q

What DMARD inhibits macrophage activation?

A

gold salts (sodium, aurothiomalate)

169
Q

What DMARD inhibits 5-LO?

A

minocycline

170
Q

What DMARD is a chimeric monoclonal antibody against CD20 on B cell surface

A

Rituximab

171
Q

What DMARD suppresses IL-1 and TNF alpha, induces apoptosis of inflammatory cells and increase chemotactic factors?

A

Sulfasalazine (SSZ)

172
Q

What does Anakinra do?

A

inhibits IL-1

173
Q

WHat does Tocilizumab do?

A

inhibist IL-6

174
Q

What is the recommended dose of methotrexate?

A

7.5-20 mg/wk

175
Q

What are the advantages of DMARDs?

A 
Slow disease progression
Improve functional disability
Decrease pain
Interfere with inflammatory processes
Retard development of joint erosions
176
Q

How long does it take for methotrexate to work? what is its potential toxicity? what are the toxicities to monitor?

A

1-3 months
moderate
hepatoxicity, pulmonary, myelosuppression

177
Q

Methotrexate blocks (blank) thus inhibiting may carbon transfer reactions and blocks (blank)

A

dihydrofolate reductase

thymidylate synthase

178
Q

What are the pros of using methotrexate (MTX, Rheumatrex)?

A

Long-term clinical experience
Favorable rate of continuation of therapy (50% - 3 yrs)
Proven efficacy in moderate to severe RA

179
Q

What are the cons of methotrexate?

A

Laboratory monitoring every 4-8 weeks

Toxicities: hepatotoxicity, myelosuppression, pulmonary (pneumonitis)

180
Q

How does sulfasalazine (asulfidine) work and what are its pros?

A

COX and lipoxygenase inhibitor

-Clinical effectiveness demonstrated in short-term use, mild level of toxicity

181
Q

What are the cons of sulfasalazine (asulfidine)?

A

Effective for mild-to-moderate RA
Contraindicated in patients with sulfa intolerance or G6PD deficiency
Toxicities: myelosuppression, gastrointestinal, decreased digoxin absorption
Rate of AEs dose-dependent
CBC every 2-4 weeks for 3 months, then every 12 weeks

182
Q

What DMARD is this:

Immunosuppressant; purine synthesis inhibitor. Prevents leukocyte proliferation

A

Azathioprine (Imuran)

183
Q

What are the pros of Azathioprine (Imuran)?

A

Effective in refractory RA

Metabolized to 6-mercaptopurine

184
Q

What are the cons of Azathioprine (Imuran)?

A

High risk for severe leukopenia and/or thrombocytopenia
Other toxicities: hepatotoxicity, may increase cancer risk, high risk for opportunistic infections, macrocytic anemia, severe bone marrow depression, GI
Requires monitoring every 1-2 weeks with dosage change, every 1-3 months thereafter; myelosupression increased with ACE-I or Allopurinol

185
Q

What DMARD blocks phagocytosis?

A

Gold Auranofin (ridaura)

186
Q

What are the pros of Gold Auranofin?

A

Effective in refractory RA
Only gold preparation for oral use
Accumulates in synovium

187
Q

What are the cons of Gold Auranofin?

A

Requires long course to determine effectiveness (6 mo.)
Toxicities: skin lesions, stomatitis, oral ulcerations, glomerulonephritis, nephrosis, thrombocytopenia, agranulocytosis
Requires close monitoring for side effects, contraindicated in hepatic or renal disease, should not be combined with other immunosuppressants; caution with X-rays.

188
Q

What is this:
Inhibits de novo pyrimidine biosynthesis through the inhibition of the mitochondrial enzyme dihydroorotate dehydrogenase.
Laboratory studies have demonstrated that it has effects on stimulated T cells.

A

leflunomide (arava)

189
Q

What are the pros of leflunomide?

A
  • early onset of action (~4 weeks)
  • stabilized benefit for long term use
  • rpevents the expansion of activated lymphocytes
  • selectively targets autoimmune lymphocytes to reduce untoward AEs
190
Q

What are the cons of leflunomide?

A

-less clinical experience
-toxicities: hepatotoxicity, GI
-expensive
long T 1/2 requires loading
-Css takes 6 months

191
Q

What are biological DMARDs?

A

Genetically engineered antibodies and proteins

192
Q

How do biological DMARDs work?

A

block the activity of immunostimulatory cytokines and other cell-signaling molecules

193
Q

What are the three categories of DMARDs?

A
  • tumor necrosis factor (TNF alpha) blockers
  • IL-1 blockers
  • anti-B cell (CD20) antibody
194
Q

What are the three drugs that are TNF alpha blockers?

A
  • etanercept (enbrel)
  • infliximab (remicade)
  • adalimumab (humira)
195
Q

What drug is an IL-1 blocker?

A

anakinra (kineret)

196
Q

What drug is an anti-B cell (CD20) antibody?

A

rituximab (rituxan)

197
Q

What is this
A dimeric fusion protein consisting of the extracellular ligand-binding portion of the human tumor necrosis factor receptor (TNFR) linked to the Fc portion of human IgG1
Binds to TNF and prevents its interaction with the TNF receptor

A

Etanercept (Enbrel)

198
Q

What is etanercept (enbrel) indicate for?

A
  • reducing signs and symptoms, including major clinical response, in RA
  • inhibiting the progression of structural damage, improving physical function in patients w/ moderately to severely active rheumatoid arthritis
  • can be initiated in combo w methotrexate (MTX) or used alone
199
Q

How do you administer Etanercept (enbrel)?

A

via injection

200
Q

What are the concerns of Etanercept (enbrel) ?

A

-fatal injections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens

201
Q

What are the common pathogens associated with fatal injections with Etanercept (enbrel)?

A

TB, histoplasmosis, aspergillosis, candidiasis, coccidioidomycosis, listerosis, and pneumocystosis

202
Q

Who should you avoid giving Etanercept (enbrel) to?

A

avoid in diabetics and anyone prone to infection

203
Q

What are adverse reactions of etanercept (enbrel)?

A
  • Injection site reactions (37%)
    a. mild to moderate erythemia and/or itching, pain or swelling but can continue drug admin
  • infection (pneumonia 7%)
  • may increase risk of malignancies
204
Q

What is this:

chimeric. mouse/human IgG1 monoclonal antibody that binds to TNFalpha with high affinity and specificity

A

Infliximab (Remicade)

205
Q

What does Infliximab (Remicade) do?

A

Binds to TNF apha which Inhibits TNF alpha binding with TNF alpha receptor

206
Q

So what is an adverse reaction to Infliximab (remicade) and how do:
you remedy it?

A

can induce allergic reactions and reduce long-term efficacy

-methotrexate could potentiate the antirheumatoid activity and reduce its immunogenicity

207
Q

What is this:
Recombinant human IgG1 monoclonal antibody specific for human TNF, and the first product consisting entirely of human peptide sequences.

A

Adalimumab (humira)

208
Q

How does adalimumab (humira) work>

A

binds to TNF alpha and blocks interaction with p55 and p75 cell surface receptors

209
Q

What is this:

Considered as a class, for patients with longstanding active RA requiring a change in therapy,

A

Biologica DMARD therapy

210
Q

Biologic DMARDs provide a (lessened/greater) symptom response and remission rate than do the oral DMARDs.

A

greater

211
Q

Should you combing biologic DMARDs with other Biologic DMARDs?

A

no, it increases risk of serious adverse effects

212
Q

What are the positives to Combo DMARD therapy (biologics with orals or orals and orals)?

A
  • does not increase toxicity levels
  • long-term outcome more favorable
  • superior efficacy to single-DMARD regimen
213
Q

What are the possible DMARD combo therapies?

A
  • methotrexate + sulfasalazine + hydroxychloroquine
  • methotrexate + cyclosporine
  • Methotrexate + leflunomide
  • methotrexate + biologic DMARD
214
Q

In patients with longstanding active RA, Combining up to (blank) oral DMARDS (MTX, sulfasalazine, hydroxychloroquine) produces greater improvements in disease activity than one or two oral DMARDs

A

3

215
Q

For patients with early RA who have not previously been treated with oral DMARDs, (blank) (sulfasalazine and MTX) does not improve symptom response, radiographic progression, or functional capacity more than monotherapy.

A

combining oral DMARDs

216
Q

In patients with inadequate disease control, biologic DMARDs used in combination with (blank) offer greater relief than monotherapy with either MTX or a biologic DMARD without increasing treatment discontinuation due to adverse effects.

A

methotrexate (MTX)

217
Q

When should DMARDs be initiated in RA?

A

early!

218
Q

DMARDs may be limited by their (blank) profiles

A

toxicity

219
Q

DMAR combo treatment is inidacted as a DMARD plus (blank)

A

methotrexate

220
Q

(blank) DMARDs are indicated when oral DMARDs are not successful

A

Biologic

221
Q

(blank) appears to be superior to oral DMARD alone in advanced disease

A

Biologic DMARDs plus Methotrexate

222
Q

The oral DMARDs, particuarly (blank), remain effective first-line treatments for RA

A

Methotrexate (MTX)

223
Q

(blank) and (blank) are similarly effective for patients with early RA, and (Blank) may provide comparable results

A

Methotrexate (MTX)
Sulfasalazine

leflunomide

224
Q

For patients with early RA who have not been treated with methotrexate (MTX-naive), treatment with either (blank) or (blank) provides similar benefits for symptoms and function. However, (blank) are more effective at limiting radiographic evidence of progression

A

MTX, biologic DMARD

Biologic DMARDs

225
Q

Adding (blank) to treatment with oral DMARDs improves function and may limit radiographic progression, although there is evidence that the combo increases the risks of adverse effects.

A

prednisone

226
Q

For patients with longstanding active disease (RA), (Blank) therapy can provide more improvement than monotherapy

A

two or three oral DMARDs in combination

227
Q

Evidence is accumulating that (blank) as a class offer greater likelihood of remission in patients with longstanding active disease than do oral ones.

A

biologic DMARDs

228
Q

COmbing (blank) provides no additional benefits and increases the risk of serious adverse effects.

A

biologic DMARDs

229
Q

In patients with inadequate disease control, (blank combined with blank) offer greater relief than monotherapy with either.

A

biologic DMARDs with methotrexate

230
Q

Which has less bad SEs, oral or biologic DMARDs?

A

neither, Oral-> toxicity
Biologics-> serious infections
Tolerability is similar b/w DMARDs of both classes

Block 7 Week 5 (8 decks)

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