MSCT Week 3: Pharmacotherapy for RA and Gout Flashcards

Question

A biosimilar product is?

Answer 1

chemically similar to FDA-approved biological product and is clinically similar to the approved product in terms of safety, purity and effectiveness

Answer 2

Must be similar to those of the approved product

Answer 3

incidence and severity of human immune response of the biosimilar product

Answer 4

Infliximab etanercept adalimumab

Answer 5

* biosimilar * a chimeric (human constant regions and mouse variable regions) anti-TNF-α monoclonal antibody

Answer 6

Anti-TNF Agents biosimilar

Answer 7

Human TNF receptor linked to the Fc portion of human IgG1 Biosimilar

Answer 8

* Anti-TNF agents * biosimilar

Answer 9

Human monoclonal Ab specific for TNF-α biosimilar

Answer 10

* Anti-TNF agents * Biosimilar

Answer 11

* IV * administer at 0, 2 and 6 weeks, then every 8 weeks

Answer 12

Given 2X/week, SC

Answer 13

* Given 1X every other week * peak plasma concentration 131+-56 hrs after administration * t1/2 = 14 days * methotrexate reduces clearance

Answer 14

Methotrexate

Answer 15

A recombinant nonglycosylated synthetic form of the human IL-1 receptor antagonist (IL-1Ra) an endogenous regulator of IL-1 action

Answer 16

* FDA approved to treat RA and neonatal-onset multisystem inflammatory disease (NOMID) * Not FDA approved but sometimes used for systemic juvenile idiopathic arthritis, adult-onset Still's Disease, Gout, Calcium pyrophosphate deposition (Pseudogout), Behcet's disease, ankylosing spondylitis, Uveitis, auto-inflammatory syndromes

Answer 17

Inhibitor of IL-12 and IL-23

Answer 18

* Indicated for the treatment of psoriatic arthritis in adults * administered alone or in combination with methotrexate

Answer 19

upper respiratory infection

Answer 20

* Fusion protein of the extracellular domain of the CTLA4 molecule and the Fc domain of human IgG1

Answer 21

Blocks the costimulatory signal required for T cell activation

Answer 22

approved for patients who do not respond well to methotrexate and for patients who do not respond to or cannot tolerate TNF antagonists

Answer 23

* 30-minute infusion given at 2 and 4 weeks after the first infusion, then every 4 weeks thereafter * Fixed-dose approximately 10 mg/kg based on weight range throughout the course of treatment

Answer 24

* Inhibitor of B cell function * A chimeric murine/human mAb against the CD20 antigen found on the surface of normal and malignant B lymphocytes

Answer 25

Include complement-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity

Answer 26

* Approved only for patients that fail to respond to anti-TNF-α therapy. * Also approved for the treatment of non-Hodgkin's Lymphoma

Answer 27

* Two-1000 mg IV infusions separated by 2 weeks * Administration of a glucocorticoid prior to each infusion is recommended in order to reduce the incidence and severity of infusion reactions

Answer 28

JAK inhibitor (Janus Kinase Inhibitor) blocks JAK 3 and JAK 1, to a lesser degree blocks JAK 2

Answer 29

FDA approved for moderately-to-severely active RA in patients who do not respond adequately to (or are intolerant of) methotrexate

Answer 30

* Inflammation of nasal passages and upper pharynx * upper respiratory tract infections * ^ risk of TB and Lymphoma * Headache

Answer 31

* increases intracell cAMP * decreases TNF-α production

Answer 32

For moderate-to-severe plaque psoriasis and for psoriatic arthritis

Answer 33

* diarrhea * nausea * nasopharyngitis * upper respiratory tract infection

Answer 34

CYP3A4 and later non-CYP mediated hydrolysis

Answer 35

58% urine 39% feces severe renal impairment need to reduce dose

Answer 36

Increased risk of depression, asses patient risk for depression and suicidal thoughts or behavior

Answer 37

deposition of monosodium urate monohydrate crystals (MSU)

Answer 38

associated with the deposition of Calcium Pyrophosphate (CPP) crystals and is sometimes referred to as calcium pyrophosphate disease (CPPD)

Answer 39

Calcium Pyrophosphate

Answer 40

Monosodium urate monohydrate crystals

Answer 41

these disorders can lead to joint destruction and renal damage

Answer 42

Recurrent Episodes of pain and joint inflammation due to the formation of crystals within the joint space and deposition of crystals in soft tissue

Answer 43

* uricase * urate * allantoin * purine metabolism

Answer 44

Hyperuricemia with serum urate level \>6.8 mg/dL

Answer 45

* Thiazide diuretics * cyclosporine * low doses of aspirin

Answer 46

Uric acid levels by itself do not precipitate gout; rather, acute changes in the level of uric acid cause gout

Answer 47

is related to renal urate underexcretion or overproduction of uric acid

Answer 48

Is related to myeloproliferative disease or their treatment, therapeutic regimens producing hyperuricemia, renal failure, renal tubular disorders, lead poisoning, hyperproliferative skin disorders, enzymatic defects (e.g. deficient hypoxanthine-guanine phosphoribosyl transferase, and glycogen storage diseases)

Answer 49

Gout has two clinical phases

Answer 50

The first phase is characterized by intermittent acute attacks that spontaneously resolve, typically over a period of 7 to 10 days with asymptomatic periods between attacks

Answer 51

With inadequately treated hyperuricemia, the transition to the second phase can occur, manifested as chronic tophaceous gout, which often involves polyarticular attacks, symptoms between attacks, and crystal deposition (tophi) in soft tissues or joints

Answer 52

Crystal Deposition

Answer 53

Tophaceous gout

Answer 54

Recurrent attacks are common

Answer 55

* NSAIDs * Colchicine * Glucocorticoids * Corticotropin

Answer 56

* NSAIDs * Colchicine * Glucocorticoids * Corticotropin

Answer 57

Colchicine and Hydroxychloroquine are effective for prophylaxis

Answer 58

* Aspirin is not indicated for treating acute gout * at lower doses aspirin causes uric acid retention by the kidney * at higher doses aspirin has a uricosuric effect

Answer 59

NSAIDs and Colchicine

Answer 60

glucocorticoids or corticotropin may be used

Answer 61

7-10 days of treatment may be necessary to ensure resolution of symptoms

Answer 62

Increased doses of anti-inflammatories are typically initially prescribed and reduced as symptoms improve

Answer 63

* Urate-lowering drugs are of no benefit in the treatment of acute gout * in general therapy with these agents should not be initiated during an acute attack * for patients already being treated with a urate-lowering agent, therapy should be continued

Answer 64

Low-dose aspirin for its protective CV effects does NOT need to be discontinued in MOST individuals

Answer 65

* in patients with hyperuricemia who have at least two gout attacks per year or tophi (as determined by either clinical or radiographic methods) urate-lowering therapy is used * The severity and frequency of flares, the presence of coexisting illnesses and patient preference are additional considerations

Answer 66

Urate-lowering therapy (ULT) should not be initiated during acute attacks but rather started 2 to 4 weeks after flare resolution

Answer 67

Urate-Lowering Therapy

Answer 68

* Start with a low initial dose and increase as needed over a period of weeks to months * Adjust dose to maintain a serum urate level \< 6 mg/dL, which is associated with a reduced risk of recurrent attacks and tophi; often the target is \<5mg/dL * Therapy is generally continued indefinitely

Answer 69

* Xanthine Oxidase Inhibitors * Uricosuric Agents * Uricase Agents

Answer 70

Data is limited

Answer 71

When the target serum urate has not been reached with a xanthine oxidase inhibitor (first-line therapy) alone

Answer 72

Block the synthesis of uric acid

Answer 73

First-line pharmacologic ULT

Answer 74

Can be used regardless of whether there is an overproduction of urate

Answer 75

A mild rash in 2% of patients

Answer 76

much less common but can be life-threatening

Answer 77

* Allopurinol * Febuxostat

Answer 78

Block the synthesis of Uric Acid

Answer 79

First-line treatment of ULT of Gout

Answer 80

* Probenecid * Lesinurad

Answer 81

Block renal tubular urate reabsorption

Answer 82

* can be used in patients with an underexcretion of urate (90% of patients with gout) they are used less frequently than xanthine oxidase inhibitors and * are contraindicated in patients with a history of nephrolithiasis

Answer 83

patients with a history of nephrolithiasis

Answer 84

In general, these drugs are ineffective in patients with renal impairment

Answer 85

Uricosuric drugs

Answer 86

A fixed-dose oral combination of lesinurad and allopurinol for treatment of hyperuricemia associated with gout who serum uric acid levels have not been achieved by allopurinol alone

Answer 87

Pegloticase

Answer 88

Uricase Agents

Answer 89

Converts uric acid into soluble allantoin

Answer 90

a polyethylene glycolated (pegylated) modified porcine recombinant uricase approved for chronic gout that is intolerant of conventional treatments

Answer 91

can be administered intravenously and infusion reactions are common

Answer 92

* Avoiding alcohol * modifying diet

Answer 93

* lowers uric acid by 1.3 mg/dL * consumption of less red meat, lowers purine levels * high intake of fruits and vegetables * increase vitamin C