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Pharmacology/Anti-cytokine Drugs - Walworth 4/7/16 Flashcards

(15 cards)

1
Q

effects of GPCR stimulation

A

Gs - increase adenylate cyclase

Gi - decrease adenylate cyclase

Gq - increase PLC

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2
Q

chemical mediators of inflammation

A
  • vasoactive amines (histamine, 5HT)
  • neuropeptides (substance P)
  • plasma proteases (Factor XII)
  • lipid-derived arachidonic metabolites
  • platelet-activating factor
  • cytokines: IL1, TNF-alpha
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3
Q

examples of diseases resulting from chronic inflammation for which anti-cytokine therapy is useful!

A
  • rheumatoid arthritis
  • inflammatory bowel disease
    • Crohn’s disease
    • ulcerative colitis
  • lupus
  • psoriasis
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4
Q

major effects of IL1 and TNFalpha

A

acute-phase rxns

  • fever
  • incr sleep
  • decr appetite
  • incr acute-phase proteins
  • hemodynamic effects (shock)
  • neutrophilia

endothelial effects

  • leukocyte adherence
  • PGI synthesis
  • incr procoag activity
  • decr anticoag activity
  • incr IL1, IL6, ILB PDGF

fibroblast effects (prolif, collagen synth, PGE, etc)

cytokine effects (incr cytokine secretion)

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5
Q

rheumatoid arthritis

  • pathophys
  • basic drugs: mech
A

pathophysiology

antigen drives lymphocyte proliferation → production of autoantibody → complement fixation, attraction of infl cells, cytokine production

  • activation of innate immune system → DCs migrate to lymph nodes, activate T cells → T cells migrate to joint → produce pro-infl cytokines
  • activated macrophages and fibroblasts → produce TNFalpha
  • more immune cells recruited to joint

drugs

DMARDs (ex. leflunomide, methotrexate)

  • prevent prolif of lymphocytes
  • reduce infl process
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6
Q

RA drugs

“cepts”

A

“TNF sponges”

etancercept: contains extracellular domain of TNFalpha-R

  • high affinity for TNFalpha → neutralization
  • indication: rheumatoid arthritis, other types of arthritis
  • admin: subcutaneous, weekly
    • often taken in combo with methotrexate
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7
Q

RA drubs

“mabs”

A

“TNF sponges” - antibody to TNFalpha

infliximab: chimeric antibody (part mouse, part human)

  • high affinity for TNFalpha → neutralization
  • admin: IV

adalimumab: humanized antibody

  • admin: subcutaneous
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8
Q

RA drugs:

anakinra

A

IL1 receptor antagonist - endogenous protein

anakinra: chimeric antibody (part mouse, part human)

  • admin: daily subcutaneous injection
    • can be given with MTX, but not TNF agents
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9
Q

RA drugs:

abatacept

A

CTLA-4-Ig

binds to B7 (aka CD80, CD86) on APC, prevents signal2 in T cell activation (B7/CD28 binding)

  • lowers serum concentration of infl mediators
  • admin: IV, 2wk, 4wk, monthly followup (shouldn’t be admin with other biologics)
    *
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10
Q

IBD

A

chronic inflammation can affect permeability of epithelial layer (make it more permeable than healthy) → amplifying loop of infl

  • Crohn’s disease (entire GI tract)
  • ulcerative colitis (colon)
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11
Q

IBD drugs

mabs

A

infliximab: chimeric antibody to TNFalpha

  • admin: IV infusion for 2 hr every 2 weeks, then every 8 weeks

certolizumab: PEGylated Fab fragment of humanized TNFalpha antibody

  • admin: subcutaneous
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12
Q

BAFF

link to disease

A

B cell Activation Factor

BlyS - B lymphocyte stimulator

member of TNFalpha family

key determinant of whether B cells will survive/die during tolerance processes!

diease link: excess BAFF in lupus

  • excess production of monoclonal antibodies
  • kidney deposition
  • complement activation

collectively, infl + tissue destruction

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13
Q

adverse effects of anti-cytokine therapy

A
  • injection site rxns
  • infusion rxns
  • cytopenia with anti-TNF therapy : need to monitor CBC
  • serious infections (sepsis, TB)
  • malignancies reported
  • hepatotox (infliximab)
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14
Q

contraindications to anti-cytokine therapy

A

active infections

  • TB+? treat latent TB first
  • pre existing demyelinating diseases
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15
Q

secukinumab

A

IL17 inhibitor → controls psoriasis

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