Immunosuppressants & Immunomodulators Flashcards

(39 cards)

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

21
Q

Corticosteroids can weaken skin in cushing syndrome by decreasing production of

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
What drug is an mTOR inhibitor?
Sirolimus
26
What is the mechanism of Sirolimus?
Sirolismus binds to mTOR (in T cell) and inhibits IL-2 synthesis.
27
What drug is a Jak/stat inhibitor?
Tofacitinib
28
What is the mechanism of Tofacitinib?
Tofacitinib inhibits dimerization of Jak and Stat proteins to prevent IL-2 and IFN-y synthesis in T cells.
29
What drugs are cytokine antibodies?
1. Adalimumab 2. Infliximab 3. Ethanercept * ends in _mab * large so must be given IV or IM
30
What is the mechanism of cytokine antibodies?
They bind to TNF-a to prevent it from binding to TNF receptor.
31
What drugs are DNA synthesis inhibitors?
1. Azathioprine (AZA) 2. Methotrexate 3. Mycophenolate
32
What is the mechanism of Azathioprine?
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
What is the mechanism of Methotrexate?
Methotrexate inhibits DHFR enzyme necessary for making folic acid, therefore DNA synthesis is inhibited.
34
What drugs are in pregnancy category D/X
AZA & Mycophenolate (D) | Methotrexate (X)
35
What drugs are cytokine receptor antibodies?
1. Anakinra 2. Rituximab 3. Tocilizumab
36
What is them mechanism of cytokine receptor antibodies?
Anakinra binds to IL-1 receptor (in many cells). Rituximab binds to CD20 (in B cells). Tocilizumab binds to IL-6 receptor.
37
What drugs are immunosuppressants/immunomodulators of transplantation?
1. Calcineurin Inhibitors 2. mTOR inhibitor 3. Azathioprine & mycophenolate 4. Rituximab
38
What drug is analgesic, anti-pyretic, and NOT anti-inflammatory?
Acetaminophen
39
What is the MoA of acetaminophen
Cox 1/2 inhibitor in the CNS only.