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Pharmacology > DMARDs and Immunomodulators > Flashcards

DMARDs and Immunomodulators Flashcards

1
Q

DMARDs - Clinical use

A

Rheumatoid arthritis – limited use (resistance to drug within 5 years, adverse effects)

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2
Q

Glucocorticoid

A

Prednisone

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3
Q

Prednisone - MoA

A

Induce formation of lipocortin which inhibits phospholipase A2, This inhibits release of arachidonic acid. Also inhibit production of cytokines (ILs, TNF)

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4
Q

Prednisone - Clinical use

A

RA to induce remission while waiting for slower-acting DMARD to work.
Short courses during flare-ups. Continuous low-dose background therapy

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5
Q

Methotrexate - Classification

A

Antineoplastic and immunomodulating drug

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6
Q

Methotrexate - MoA

A

Inhibition of human folate reductase which decreases thymidylate and DNA synthesis.

Inhibition of lymphocyte proliferation and production of cytokines and rheumatoid factor.

Interferes with polymorphonuclear leukocyte chemotaxis, which reduces cytotoxins and free radicals

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7
Q

Methotrexate - Clinical use

A

DMARD of choice in most patients with RA

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8
Q

Methotrexate - Contraindications

A

Pregnancy and in combination with leflunomide because of hepatotoxicity

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9
Q

Methotrexate - Adverse effects

A

GI, hematologic, hepatic, pulmonary reactions.

Elevated liver enzymes.

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10
Q

Leflunomide - Classification

A

Immunosuppressive drug

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11
Q

Leflunomide - MoA

A

Inhibits leukocyte and T-cell proliferation by inhibiting pyrimidine synthesis (DNA replication, RNA synthesis, protein synthesis) in immune cells

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12
Q

Leflunomide - Clinical use

A

Alternative to methotrexate for RA

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13
Q

Leflunomide - Contraindications

A

Pregnancy and in combination with methotrexate because of hepatotoxicity

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14
Q

Leflunomide - Adverse effects

A

Diarrhea Reversible alopecia (baldness)
Increased serum hepatic enzymes
Teratogenic

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15
Q

Leflunomide - Interactions

A

Inhibition of CYP2C9: increases serum levels of many drugs (ibuprofen)

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16
Q

Hydroxychloroquine - Classification

A

Antimalarial drug

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17
Q

Hydroxychloroquine - MoA

A

Reduces chemotaxis and phagocytosis of PMNs, reduced superoxides from these cells

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18
Q

Hydroxychloroquine - Adverse effects

A

Blurred vision, scotomas, night blindness

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19
Q

Anti TNF-α agents

A 
Etanercept 
Infliximab 
Adalimumab 
Cetrolizumab 
Golimumab
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20
Q

Anti TNF-α agents - MoA

A

Binds to and inactivates TNF-α. Newer agents prevents interleukin binding and T-cell activation.

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21
Q

Anti TNF-α agents - Adverse effects

A

Serious infections and sepsis
Tuberculosis and invasive opportunistic fungal infections
Lymphoma

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22
Q

Etanercept - MoA

A

Dimer of human TNF receptor fused to IgG constant region

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23
Q

Etanercept - Clinical use

A

RA resistant to other DMARDs

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24
Q

Etanercept can be combined with

A

Methotrexate

25
Q

Etanercept - Adverse effects

A

Injection site reactions

26
Q

Infliximab - MoA

A

MAb binds to TNF-α and prevents it from activating TNF-α receptor

27
Q

Infliximab - Clinical use

A

Crohn’s disease and rheumatoid arthritis

ankylosing spondylitis, psoriatic arthritis* *=Katzung

28
Q

Infliximab can be combined with

A

Methotrexate

29
Q

Infliximab - Adverse effects

A

Hypersensitivity reactions
Infection
Malignancy
Reactivation of latent TB

30
Q

Adalimumab - MoA

A

Human IgG1 MAb similar to daclizumab, specific for human TNF α

31
Q

Cetrolizumab - MoA

A

Pegylated Mab directed against TNF α.

32
Q

Golimumab - MoA

A

Human Mab that binds to both the soluble and transmembrane forms of human TNFα. This interaction prevents the binding of TNFα to its receptor, thereby inhibiting the biologic activity of TNFα.

33
Q

Cytokine inhibitors

A

Anakinra
Canakinumab
Rilonacept

34
Q

Anakinra - MoA

A

Recombinant form of the human interleukin- 1 receptor antagonist (IL-1Ra). Blocks the biologic activity of IL-1 by competitively inhibiting IL-1 binding to the interleukin-1 type I receptor (IL-1RI).

35
Q

Anakinra - Clinical use

A

RA, Gout

36
Q

Canakinumab - MoA

A

Recombinant human anti-IL-1β monoclonal antibody. It binds to human IL-1β and prevents it from binding to IL-1 receptors.

37
Q

Rilonacept - MoA

A

Dimeric fusion protein consisting of the ligand-binding domains of the extracellular portions of the human interleukin-1 receptor component (IL-1RI) and IL-1 receptor accessory protein (IL-1RAcP) fused to the Fc portion of human IgG1.

38
Q

Abatacept - MoA

A

Selective costimulation modulator, inhibits T-cell activation by binding to cell surface markers (proteins) in leukocytes.

39
Q

Abatacept - Clinical use

A

RA, Sjögren, Psoriasis

40
Q

Tocilizumab - MoA

A

Humanized anti-IL-6 receptor Mab. Binds selectively to IL-6 receptors and blocks IL-6 acitivity.

41
Q

Tocilizumab - Clinical use

A

RA

Active systemic juvenile idiopathic arthritis in patients 2 y and older

42
Q

Sulfasalazine - Clinical use

A

RA

43
Q

Sulfasalazine - Contraindication

A

Sulfa-allergy

44
Q

D-Penicillamine - MoA

A

Reduces blood levels of inflammation cytokines

45
Q

D-Penicillamine - Clinical use

A

RA Less used, better alternatives today.

Copper chelating agent in Willsons disease

46
Q

Apremilast - MoA

A

Inhibitor of phosphodiesterase type 4 (PDE4) –> increases cAMP levels, which decreases expression of TNFα and other proinflammatory cytokines.

47
Q

Which cytokine inhibitor has the same adverse effects as the TNFα blockers?

A

Anakinra

48
Q

Aldesleukin - MoA

A

Recombinant interleukin-2

49
Q

Aldesleukin - Clinical use

A

Adjunctive treatment of renal cell carcinoma and malignant melanoma.

50
Q

Daclizumab - MoA

A

Highly specific MAb that binds to the alpha subunit of the IL-2 receptor displayed on the surface of T cells and prevents activation by IL-2

51
Q

Daclizumab - Clinical use

A

Prevent renal transplant rejection. In comb with other immunosuppressants

52
Q

Interferon–α-2a - MoA

A

Inhibits cell proliferation

53
Q

Interferon–α-2a - Clinical use

A

Hairy cell leukemia, chronic myelogenous leukemia, malignant melanoma, Kaposi’s sarcoma, Hepatitis B and C.

54
Q

Interferon-b-1b - Clinical use

A

Relapsing multiple sclerosis

55
Q

Interferon-g-1b - MoA

A

Greater immune-enhancing actions. Act by increasing the synthesis of TNF.

56
Q

Interferon-g-1b - Clinical use

A

Recombinant form: decrease the incidence and severity of infections in patient with chronic granulomatous disease

57
Q

Canakinumab - Clinical use

A

Gout, Systemic juvenile arthritis

58
Q

Rilonacept - Clinical use

A

Gout, RA

59
Q

Sulfasalazine - MoA

A

Suppress T cell response to concanavalin, inhibit B-cell proliferation, and release of inflammatory cytokines.

Pharmacology (55 decks)

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