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HMS IDD > Immunosuppressants > Flashcards

Immunosuppressants Flashcards

1
Q

Major classes of immunosuppressants

A
  • Corticosteroids
  • Cyclophilin-binding drugs
  • Immunosuppressant anti-metabolites
  • Antibodies
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2
Q

Most important clinical corticosteroids

A
  • Methylprednisone
  • Presdnisolone
  • Prednisone
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3
Q

Effects of corticosteroids in various tissues

A
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4
Q

Complications of chronic corticosteroid use

A
  • Bone loss
  • Peptic ulcers
  • Hypertension
  • Infection
  • Increased blood glucose
  • Osteonecrosis
  • Weight gain
  • Cataracts
  • Striae (stretch marks)
  • Muscle atrophy
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5
Q

The hypothalamic-pituitary-adrenal axis

A
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6
Q

The cyclophilin binding drugs

A
  • Cyclosproine & Tacrolimus: Bind NF-AT
  • Sirolimus (Rapamycin) & Everolimus: Bind mTOR
  • Both groups serve to impede T cell growth, activation, and mediator production
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7
Q

When do we use cyclophilin binding drugs?

A
  • Most importantly, FOR TRANSPLANTS to prevent rejection
  • Also, to treat T cell-mediated diseases: Psoriasis, RA, Crohn’s, atopic dermatitis
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8
Q

Cyclosporine A mechansitic diagram

A
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9
Q

Complications and toxicities of cyclosporine

A
  • Infection (obviously)
  • Cancer (obviously)
  • Hypertension
  • Renal toxicity
  • Hepatic toxicity
  • Tremor
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10
Q

Tacrolimus (aka FK506) mechanistic diagram

A
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11
Q

mTOR

A

Member of the phosphatidylinositol 3- kinase-related kinase protein family;

it is a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, transcription

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12
Q

TCR and IL-2R pathways

A
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13
Q

Immunosuppressive antimetabolites

A
  • Inhibit cell replication and thus affect immune system because it has the most rapidly dividing natural human cells
  • Methotrexate
  • Mycophenylate
  • Azathioprine
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14
Q

Methotrexate

A
  • First line therapy for RA
  • Dose dependent liver fibrosis is a toxicity
  • Incompatible with pregnancy
  • An antifolate
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15
Q

Azathioprine

A
  • Pro-drug which is converted into 6-mercaptopurine then into thioinosinic acid once inside of cell
  • Thioinosinic acid inhibits DNA synthesis
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16
Q

Mycophenylate

A
  • Converted into mycophenylic acid
  • Inhibits inosine monophosphate dehydrogenase, an ezyme involved in nucleotide biosynthesis
  • Fairly selective action at inhibiting T and B cell proliferation
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17
Q

alemtuzumab

A

Anti-CD52

Depletes both T and B cells

18
Q

Main concern with anti-TNFs

A

Infection! Many possible infections (viral, bacterial, fungal, etc etc)

But not so much cancer

19
Q

Anti-cytokine antibodies associated with infection risk

A
  • TNFa
  • IL-2
20
Q

Anti-cytokine antibodies associated with relatively normal risk of infection

A
  • IL-6
  • IL-17
  • IL-23
  • IL-4
21
Q

Anti-Th17-cytokines

A
  • Ustekinumab - anti-IL-23R
  • secukinumab, ixekizumab - anti-IL-17A
  • brodalumab - anti-IL-17R
22
Q

Major cytokine-depleting antibody diagram

A
23
Q

At what stages are B cells CD20+?

A
24
Q

Antithymocyte globulin

A
  • Polyclonal antibodies produced by immunizing orthologous species against human lymphoid tissue and harvesting the resultant sera
  • Approved for treatment of acute cellular rejection and used as induction agent
25
Q

Antibiotics with immunosuppressive effects

A
  • Low dose doxycycline
  • tetracycline
  • minocycline
26
Q

Antimalarials with immunosuppressive effects

A
  • Hydroxychloroquine
  • Chloroquine
  • Quinacrine
27
Q

Jak/STAT inhibitors

A
28
Q

Progressive multifocal leukoencephalopathy (PML)

A
  • rare and usually fatal virally mediated brain inflammation
  • John Cunningham virus (JCV), human polyomavirus
  • Latent virus present in GI tract in healthy controls, viral shedding occurs, suppressed by immune system
  • Observed in immunocompromised (HIV, lymphoma/leukemia, autoimmune diseases, immunosuppressant Rx)
29
Q

What do you need to screen for before immunosuppressing someone?

A
  • Watch patients carefully! Report fevers, chills, muscle aches promptly
  • Latent TB
  • Hepatitis B and C
  • HSV
  • VZV
  • JCV
  • Polyomavirus
  • Toxoplasma
  • Pneumocystis
  • Candidiasis
30
Q

HAART

A
  • Highly active antiretroviral therapy
31
Q

Cancers associated with T cell immunosuppression

A
  • Mostly virally-mediated cancers
  • Kaposi’s sarcoma (Human Herpes virus 8 / HHSV8)
  • Oral, cervical, throat and anal squamous cell cancers (human papilloma virus / HPV)
  • Lymphomas (Epstein Barr virus / EBV)
  • Merkel cell carcinomas (Merkel cell polyomavirus)
  • Liver cancer (Hepatitis B, Hepatitis C)
  • Non-infectious cancers: lung, kidney cancer, skin squamous cell carcinomas
32
Q
A

Oral Kaposi’s sarcoma

33
Q

Best treatment for Kaposi’s sarcoma

A

Reduction of dosage of immunosuppression

34
Q

Best treatment for immunosuppression-associated mucosal squamous cell carcinomas

A

excision, radiation, chemo

35
Q
A

Merkel Cell Carcinoma

36
Q

Potential infectious causes of lymphoma

A
  • EBV
    HIV
  • Human T cell leukemia virus-1 (HTLV-1)
  • Hepatitis C
  • HHV8
  • H. pylori
37
Q

Leading cause of death in solid organ transplant patients

A

Immunosuppression-induced squamous cell carcinoma of the skin

38
Q

Risk of SSC in transplant patients is associated with

A
  • Sun exposure
  • Depth of T cell immunosuppression
  • Which T cell immunosuppressant is used (highest risk is with cyclosporine, lowest is with mTOR inhibitors)
39
Q

Managing risks of SCC for transplant patients

A
  • Strict sun protection and dermatology followups
  • Use minimum possible level of immunosuppression
  • Switch to mTOR inhibitors if possible and well tolerated
40
Q

__ + __ = squamous cell carcinoma

A

sun exposure + cyclosporine = squamous cell carcinoma

41
Q

People with HIV have too ___ T cell immunity

A

People with HIV have too little AND too much T cell immunity

In other words, they have too few proinflammatory CD4 T cells for proper protection, and too few Tregs for proper tolerance

HMS IDD (28 decks)

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