Pharm: Anti-inflammatory and Corticosteroids Flashcards

1
Q

What are the drugs of first choice for RA due to efficacy and rapid onset of action?

A

NSAIDs

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2
Q

What is important to remember about using NSAIDs for RA?

A

Do NOT alter disease progression

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3
Q

What is the important role of using glucocorticoids in managment of RA; which have longer half-lifes and potency?

A
  • Relieves pain and inflammation while waiting for DMARD effects
  • Fluorinated prednisolones: Betamethasone, Dexamethasone, Triamcinolone
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4
Q

How can exogenous glucocorticoids be fatal?

A

If abruptly stopped, rather than discontinuing slowly

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5
Q

Which DMARD is the drug of first-choice for RA?

A

Methotrexate

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6
Q

RA pt’s taking low doses of methotrexate should also take what?

A

Weekly folate supplements

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7
Q

What are the life-threatening major toxicities associated with higher doses of Methotrexate?

A
  • Bone marrow suppression
  • Hepatic fibrosis
  • GI ulceration
  • Pneumonitis
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8
Q

What is the MOA of low-dose Methotrexate used for RA?

A
  • Polyglutamation –> MTX-(glu)n which accumulates in cells
  • Blocks thymidylate synthase and AICAR
  • AICAR causes Adenosine efflux which binds purinergic GPCRs –> anti-inflammatory effect
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9
Q

What is the MOA of Hydroxycloroquine used in RA; how quick is onset?

A
  • Lipophilic weak base –> accumulates in lysosomes –> ↑ pH
  • ↑ pH of lysosome in APC’s limits the assoc. of peptides w/ class II MHC
  • Can slow disease progression, but delayed onset (3-6 mo.)
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10
Q

Which DMARD can a pregnant mother with RA use safely?

A

Hydroxychloroquine

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11
Q

What is a rare dose-related, but serious, AE of Hydroxychloroquine?

A

Retinal damage

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12
Q

What is the active metabolie of the DMARD Sulfasalazine when used for RA?

A

Sulfapyridine

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13
Q

What is the MOA of the DMARD, Leflunomide?

A
  • Inhibition of mitochondrial enzyme dihydroorotate dehydrogenase to block synthesis of rUMP and pyrimidine synthesis
  • Inhibits T cell proliferation (especially memory T cells)
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14
Q

Which traditional DMARD disrupts pyrimidine synthesis and is a 2nd choice due to more common serious AE’s?

A

Leflunomide

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15
Q

5 most common AE’s assoc. w/ the DMARD, Leflunomide?

A
  • Diarrhea
  • Respiratory infection
  • Reversible alopecia
  • Rash
  • Nausea
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16
Q

The DMARD, leflunomide is toxic to which organ?

A

Hepatotoxic –> ↑ risk of serious infections

17
Q

What is the rule for using biologic and non-biologic DMARDs together?

A
  • CAN combine biologics and non-biologics
  • Biologics should NEVER be combined w/ other biologics
18
Q

What are the 3 TNF-α blockers used for RA?

A
  • Etanercept
  • Infliximab
  • Adalimumab
19
Q

What is the clinical indication for using the TNF-α blockers (etanercept, infliximab, and adalimumab) for RA?

A

Moderate to severe RA, gen. after traditional DMARDs have been ineffective

20
Q

What are some of the serious AE’s associated with the TNF-α blockers used for RA?

A
  • Serious infections: including tuberculosis
  • Pt’s may also experience severe allergic reactions
21
Q

Which drug targets CD20 antigen of B cells to cause a B cell ‘do-over,’ and is used to treat HL and CLL + in combo with MTX for RA in those who have no responded to TNF-blockers?

A

Rituximab

22
Q

What testing in a pt with RA would indicate a greater likelihood of response to Rituximab?

A

(+) testing for rheumatoid factor or anti-cyclic citrullinate peptide (CCP)

23
Q

Rituximab is associated with what serious AE?

A

Severe infusion related hypersensitivity rxns

24
Q

What is the MOA of Abatacept used for RA?

A

Prevents CD28 from binding to its counter-receptor, CD80/CD86

25
Q

What is the MOA and effects of Tocilizumab used for RA?

A
  • Humanized anti-human IL-6 receptor antibody
  • Limits hepatic acute phase response and activation of T cell, B cells, macrophages, and osteoclasts
26
Q

What is the most common AE and a serious AE of Tocilizumab?

A
  • Most common = upper respiratory tract infections
  • Serious = life-threatening infections (TB, invasive fungal infections, opportunistic, etc.)
27
Q

Which biologic DMARD used for RA stands out due to it being available as an oral formulation?

A

Tofacitinib - JAK3 antagonist

28
Q

What is the MOA of Tofacitinib used for RA?

A

Inhibitor of JAK3 –> directly suppresses the prod. of IL-17 and IFN-y and the proliferation of CD4+ T cells

29
Q

What are AE’s associated with Tofacitinib and which warning comes with this drug?

A
  • Serious and sometimes fatal infections due to bacteria, mycobacterial, invasive fungal and other opportunistic pathogens
  • Warning = ↑ risk of malignancies (i.e., lymphoma)
30
Q

What is the MOA of Anakinra used for RA; clinical indication?

A
  • A recombinant non-glycosylated version of human IL-1 receptor antagonist–> blocks the pro-inflammatory activity of naturally occurring IL-1
  • Less efficacious than others, so used as late choice
31
Q

Which TNF-antagonist consists of two TNF receptors bound to Fc portion of IgG and is administered 1-2x/weekly by SQ injection?

A

Etanercept

32
Q

The TNF-antagonist, Etanercept is effective in treating what conditions?

A

RA + psoriatic arthritis + ankylosing spondylitis