Rx Chemotherapeutics

- AML

- Non-Hodghkin's Lymphoma

Anthracycline

- Derived from streptomyces

- Intercalating agent (stops

DNA replication, leading to 

strand breaks etc..

- AML

- ALL

Thalidomide

Lenalidomide

- High risk of VTE!!! especially when
  used with corticosteroids 

  (Hyperviscocity)

- Recommend Low Dose ASA (at least)

- Teratogenic

- 

Proteosome inhibitor

- Proteosome is a cellular

garbage collector (removing

misfolded proteins). 

- Pro-apoptotic factors get

removed by proteosome

preventing cancer apoptosis.

Binds tubulin dimers, arrests

mitosis in metaphase

- Toxicity: low blood counts

- Need PCP and anti-HSV prophylaxis

Highly effective therapy, if doesn't

respond, consider other dx.

Indications:

Multiple Myeloma

...

Mechanism:

- 

Thalidomide Side Effects:

- Somnolence

- Constipation

- Peripheral Neuropathy

Lenalidomide Side Effects:

- Myelosuppression

Cautions:

- Teratogenic

- High risk of VTE (esp if used with steroids)

  Recommend at least low-dose ASA for prophylaxis

Indications:

Multiple Myeloma

Mantle Cell Lymphoma

Mechanism:

- Proteosome inhibitor

(proteosome is like a 

"garbage disposal")

- When inhibited cells

undergo apoptosis.

Side Effects:

- Peripheral Neuropathy

- Thrombocytopenia

Cautions:

- Teratogenic

- High risk of VTE (esp if used with steroids)

  Recommend at least low-dose ASA for prophylaxis

Indications:

Multiple Myeloma

Mechanism:

- Alkylating Agent

- Old drug for MM

Side Effects:

- Myelosuppression

- Stem cell toxicity

Cautions:

- Not used in induction for pts that are candidates for autologous HSCT

Inhibits ribonucleotide

reductase (decr. ribonucleotides)

- Sickle Cell Disease

- Essential Thrombocythemia

- Polycythemia Vera

- Monitor CBCs q2w

- Terratogenic (need contraception)

- Increases MCV - can monitor compliance

Mycophenylate Mofetil

(Cellcept)

Mycophenylate Mofetil = prodrug to

improve bioavailability (converts to

mycophenolic acid)

Use:

- Renal Transplant

- Also liver, heart, lung transplants

- Autoimmune Diseases (Behcets,

  pemphigus, refractory SLE

  small vessel vasculitis, psoriasis)

Mechanism: Inhibits B and T-cell

  proliferation.

- Increases cholesterol levels

- Monitor BUN, Lytes, Ext-Lytes

NOTE: Typically azathioprine

  preferred in autoimmune cond

  b/c lower incidence of diarrhea.

Tacrolimus

(Prograf, Advagraf)

Use: Allogeneic organ transplant

- Liver Transplants (first use in 1994)

- Kidney, heart, small bowel, pancreas

  lung, trachea, skin, cornea, bone

  marrow, limb transplants

- Topical: atopic dermatitis

First macrolide immunosuppressant

was sirolimus (rapamycin), this was

second.  Produced by Streptomyces

tsukubaensis in soil.

Mechanism: Macrolide calcineurin

inhibitor.  Inhibits calcineurin (activated

by high Ca2+ levels in activated T-cells)

Prevents phosphorylation of NF-AT,

nuclear factor for activated T-cells,

thereby preventing transcription of

T-cell signaling and IL-2.

- Renal monitoring (Tacrolimus

  Nephrotoxicity)

- Note: mechanism similar to 

  ciclosporin but tacro shown to have

  lower acute rejection rates.

- Interacts with grapefruit and

  antifungals

- Topical preparations used for

  atopic

Ciclosporin

(calcineurin inh.)

Use: Allogeneic organ tarnsplant.

Mechanism: It is a cyclic non-ribosomal

peptide that inhibits T-cell inhibitor.

- Binds cyclophilin -> inhibits calcineurin

(calcineurin allows transcr. of IL2, etc.)