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Immunology-Week 3 & 4 > Immunosuppressants & Immunomodulators > Flashcards

Immunosuppressants & Immunomodulators Flashcards

1
Q

What are eicosanoids?

A

Signaling molecules derived from FA (plasma membrane lipids –> Arachidonic Acid (AA) –> eicosanoids

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2
Q

What enzymes are involved in eicosanoids production?

A
  1. Phospholipases (PLA2): plasma membrane lipids –>AA

2. Cyclooxygenase (Cox 1/2): AA –> eicosanoids

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3
Q

What are eicosanoids/prostanoids we have to know?

A

Prostaglandins (PGE2) & Thromboxanes (TXA2)

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4
Q

What is the MoA of Cox Inhibitors?

A

Inhibit the synthesis of prostanoids

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5
Q

What is the main role of COX 1 & 2?

A

Cox 1 is constitutive (maintains homeostatic function)

  • Renal, GI, Platelet formation
  • Usually produce toxic effects when inhibited

Cox 2 is inducible (promote inflammatory response)

  • Pain, fever, inflammation
  • Usually produce therapeutic effects when inhibited
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6
Q

What are main COX inhibitors and their toxicities?

A

NSAIDS

  • Gastic Damage (bleeding, ulcers)
  • Nephron/kidney damage
  • Inhibits platelet activation & clotting
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7
Q

What is the MoA of NSAID for Gastic Damage?

A

NSAIDs inhibit PGE2 (important mucosal component) which leads to weakened mucous layer in the stomach (bleeding, ulcers).

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8
Q

What is the MoA of NSAID for Nephron Damage?

A

NSAIDs inhibit PGE2 (vasodilator) acting on glomerulus of kidney which leads to nephron damage.

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9
Q

What is the MoA of NSAID for Platelet Inactivation?

A

NSAIDs inhibit TXA2 (promotes platelet activation) which leads to clotting inability.

  • NSAIDs can provide therapeutic effect for type II MI/stroke in older patients.
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10
Q

How is Asprin used off-label as a treatment?

A

Aspirin is used in conjunction with IVIG to treat kawasaki

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11
Q

What are examples of Aspirin toxicity?

A
  1. Reye’s Syndrome (when given asprin during viral infections)
  2. Bronchoconstriction (causes aspirin-sensitive asthma by promoting production of brochoconstricting products)
  3. Acute & Chronic Aspirin Poisoning
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12
Q

What asprin-related drugs can cause chronic aspirin poisoning?

A

subsalicylate

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13
Q

What NSAIDs are non-selective (affect COX 1/2)?

A
  1. Ibuprofen
  2. Naproxen
  3. Aspirin
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14
Q

What NSAIDs are selective COX-2 inhibitors?

A
  1. Celecoxib

2. Rofecoxib

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15
Q

What is the advantage of selective COX-2 inhibitors?

A

fewer GI toxicities

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16
Q

What is the disadvantage of selective COX-2 inhibitors?

A

more CV toxicities like heart attack because COX-2 inhibitors also inhibit the prostacyclin (PGI2) synthesis which are anti-clotting.

17
Q

What are coticosteroid drugs we have to know?

A
  1. Hydrocortisone
  2. Prednisone
  3. Methylprednisolone
  4. Dexamethasone
18
Q

What are 2 therapeutic mechanisms of Corticosteroids?

A
  1. Inhibit pro-inflammatory cytokines
  2. Increase anti-inflammatory lipocortin/annexin 1 (inhibits PLA2)
    * Both mechanisms alter the gene transcription in target cells
19
Q

What are examples of corticosteroid toxicities?

A
  1. Oral inhalation (like inhaler for asthma) can cause thrush and penumonia.
  2. Cushing Syndrome (aka. hypercortisolim) including affected skin and bones.
20
Q

Corticosteroids can weaken bone in cushing syndrome by decreasing production of

A

osteocalcin

21
Q

Corticosteroids can weaken skin in cushing syndrome by decreasing production of

A

keratin

22
Q

What drugs are calcineurin inhibitors?

A
  1. Cyclosporin

2. Tacrolimus

23
Q

What is the mechanism of calcineurin inhibitors?

A

They inhibit T cell activation by binding to calcineurin to prevent TCR signaling to produce more IL-2.

24
Q

What is the most common calcineurin toxicity?

A

Non-Hodgkin’s lymphoma

25
Q

What drug is an mTOR inhibitor?

A

Sirolimus

26
Q

What is the mechanism of Sirolimus?

A

Sirolismus binds to mTOR (in T cell) and inhibits IL-2 synthesis.

27
Q

What drug is a Jak/stat inhibitor?

A

Tofacitinib

28
Q

What is the mechanism of Tofacitinib?

A

Tofacitinib inhibits dimerization of Jak and Stat proteins to prevent IL-2 and IFN-y synthesis in T cells.

29
Q

What drugs are cytokine antibodies?

A
  1. Adalimumab
  2. Infliximab
  3. Ethanercept
  • ends in _mab
  • large so must be given IV or IM
30
Q

What is the mechanism of cytokine antibodies?

A

They bind to TNF-a to prevent it from binding to TNF receptor.

31
Q

What drugs are DNA synthesis inhibitors?

A
  1. Azathioprine (AZA)
  2. Methotrexate
  3. Mycophenolate
32
Q

What is the mechanism of Azathioprine?

A

AZA has 2 products: both leading to cell death

  1. inhibit purine synthesis
  2. aberrant nucleotide incorporated into DNA (this product can act like mutation and lead to leukemia and carcinoma)
33
Q

What is the mechanism of Methotrexate?

A

Methotrexate inhibits DHFR enzyme necessary for making folic acid, therefore DNA synthesis is inhibited.

34
Q

What drugs are in pregnancy category D/X

A

AZA & Mycophenolate (D)

Methotrexate (X)

35
Q

What drugs are cytokine receptor antibodies?

A
  1. Anakinra
  2. Rituximab
  3. Tocilizumab
36
Q

What is them mechanism of cytokine receptor antibodies?

A

Anakinra binds to IL-1 receptor (in many cells).

Rituximab binds to CD20 (in B cells).

Tocilizumab binds to IL-6 receptor.

37
Q

What drugs are immunosuppressants/immunomodulators of transplantation?

A
  1. Calcineurin Inhibitors
  2. mTOR inhibitor
  3. Azathioprine & mycophenolate
  4. Rituximab
38
Q

What drug is analgesic, anti-pyretic, and NOT anti-inflammatory?

A

Acetaminophen

39
Q

What is the MoA of acetaminophen

A

Cox 1/2 inhibitor in the CNS only.

Immunology-Week 3 & 4 (11 decks)

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