Pharm: Anti-inflammatory and Corticosteroids

Question 1

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

Answer 1

Retinal damage

Question 2

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

Answer 2

• Diarrhea
• Respiratory infection
• Reversible alopecia
• Rash
• Nausea

Question 3

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

Answer 3

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

Question 4

What is the MOA of the DMARD, Leflunomide?

Answer 4

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

Question 5

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

Answer 5

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

Question 6

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

Answer 6

• 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.)

Question 7

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

Answer 7

• Etanercept
• Infliximab
• Adalimumab

Question 8

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

Answer 8

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

Question 9

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

Answer 9

Etanercept

Question 10

What is important to remember about using NSAIDs for RA?

Answer 10

Do NOT alter disease progression

Question 11

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

Answer 11

• 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

Question 12

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

Answer 12

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

Question 13

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

Answer 13

RA + psoriatic arthritis + ankylosing spondylitis

Question 14

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

Answer 14

Weekly folate supplements

Question 15

Rituximab is associated with what serious AE?

Answer 15

Severe infusion related hypersensitivity rxns

Question 16

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

Answer 16

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

Question 17

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

Answer 17

Sulfapyridine

Question 18

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

Answer 18

Leflunomide

Question 19

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

Answer 19

• Bone marrow suppression
• Hepatic fibrosis
• GI ulceration
• Pneumonitis

Question 20

What is the MOA of Abatacept used for RA?

Answer 20

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

Question 21

What is the MOA of Tofacitinib used for RA?

Answer 21

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

Question 22

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

Answer 22

Methotrexate

Question 23

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

Answer 23

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

Question 24

How can exogenous glucocorticoids be fatal?

Answer 24

If abruptly stopped, rather than discontinuing slowly

Question 25

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

Answer 25

NSAIDs

Question 26

Which DMARD can a pregnant mother with RA use safely?

Answer 26

Hydroxychloroquine

Question 27

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

Answer 27

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

Question 28

The DMARD, leflunomide is toxic to which organ?

Answer 28

Hepatotoxic –> ↑ risk of serious infections

Question 29

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

Answer 29

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

Question 30

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?

Answer 30

Rituximab

Question 31

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

Answer 31

Tofacitinib - JAK3 antagonist

Question 32

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

Answer 32

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