Miscellaneous

Question 1

Colchicine

Answer 1

• “Microtubule poison”
• Class: uricosuric agent
• MOA: Binds and stabilizes tubulin to inhibit microtubule polymerization → impaired leukocyte chemotaxis and degranulation
  
  • It inhibits neutrophil motility, activity, and degranulation leading to a net anti-inflammatory effect
• Precautions: narrow therapeutic window
• AEs: diarrhea, vomiting, and other GI side effects, agranulocytosis (myelosuppression: crushes myeloblasts and promyelocytes), myopathy

Question 2

Anakinra

Answer 2

• Class: IL-1 receptor antagonist
• MOA: binds to IL-1 receptor → inhibition of IL-1 actions → prevention of IL-1β-mediated inflammation (e.g., in FMF)
• AEs: neutropenia, ⇡risk of infection (b/c it is blocking the inflammation pathway, which can be used to fight infection)

Question 3

Rituximab

Answer 3

• Class: anti-CD20 monoclonal antibody
• MOA: Rituximab binds to CD20 on the surface of malignant B cells → rituximab’s Fc domain recruits immune effector functions → complement-dependent B cell cytotoxicity and antibody dependent cellular toxicity
• Use: Follicular lymphoma (symptomatic patients)
  
  • Malignant B cells usually express CD20 on their cell surface
  • CD20 regulates cell cycle initiation and differentiation
• Adverse Reactions:
  
  • Some have been fatal → it is important to infuse rituximab slowly
  • Infusion reactions (typically during first infusion)
  • Chills and fevers commonly accompany first infusion because of the rapid activation of complement → release of TNF-α, IL-1, & IL-6
  • Hypotension
  • Bronchospasm
  • Angioedema
  • Cardiac arrythymias
  • **Tumor lysis syndrome (hyperkalemia, hypocalcemia, hyperuricemia, hyperphosphatemia → acute renal failure → dialysis) **
  • Leukopenia, thrombocytopenia and neutropenia

Question 4

Ruxolitinib

Answer 4

• Class/MOA: Janus kinase inhibitor
  
  • ​Inhibits dysregulated JAK1 and JAK2 signaling in ALL
  • JAK1 and JAK2 recruit signal transducers and activators of transcription (STATs) to cytokine receptors → modulation of gene expression

Question 5

Mycophenolic acid (MPA)

Answer 5

• Use: Moderate SLE and Lupus nephritis
• MOA: MPA is an inhibitor of inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in the formation of guanosine in **de novo purine synthesis by lymphocytes → **inhibition of lymphocyte proliferation & antibody production
  
  • lymphocytes are dependent on the de novo pathway of purine synthesis
  • MPA preferentially inhibits type II IMPDH, the isoform expressed mainly in lymphocytes
• Side effects: HTN and diarrhea

Question 6

NSAIDS

Answer 6

• MOA:
  
  • Inhibition of COX reduces the intermediates and downstream products in the pathway for the synthesis of prostaglandins (PGs).
  • Aspirin causes covalent modification (acetylation) of COX 1 & 2.
  • COX inhibition reduces Thromboxane A2 (TXA2) production in platelets.
  • Since platelets are non-nucleated, loss of platelet aggregation will continue for the lifetime of the platelet (~7-10 days) until more platelets are made.
  • Low dose aspirin → most inhibition of COX1 → ⇣ TXA2 production in platelets.
  • COX2 activity is needed for expression of prostacyclin (PGI2) in endothelial cells.
  • Advantage of a low dose of aspirin is that it causes loss of TXA2 without losing PGI2.
  • PGI2 has vasodilatory and anti-platelet effects, so inhibition of TXA2 without inhibition of PGI2 is desirable.

Question 7

Corticosteroids

Answer 7

Anti-inflammatory and immunosuppressive effects mediated by interactions with glucocorticoid response elements and inhibition of transcription factors such as NF-κB

Question 8

Triamcinolone acetonide

Answer 8

Binds to glucocorticoid receptors, inhibiting the transcription of many different AP-1- and NF-κB-dependent genes, including IL-1 and TNF-α. → decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversal of increased capillary permeability

Question 9

Palivizimab

Answer 9

= humanized anti-RSV antibody

• Given to premies
• Monthlyh IM administration to high-risk patients (e.g., immunocompromised) during epidemic periods (November - January in NY)