Anti-Resorptives, Anti-Angiogenics, Anti-Neoplastic, and Immunosuppressive Drugs

Question 1

Bisphosphonates

Answer 1

Mech: Bisphosphonates adhere to bony surfaces undergoing active resorption. During resorption, the drug is released which impairs the osteoclasts ability to form the “ruffled border” and adhere to the bony surface. It also inhibits osteoclastogenesis and cause apoptosis of osteoclasts.

“-dronates”

Clodronate (Bonefos, Loron, Ostac) : Oral/IV, low potency
Zoledronate (Zometa): IV only, highest potency
Palmidronate (Areida)
Alendronate (Fosemax)
Ibandronate (Boniva)
Risedronate (Actonel)

Question 2

RANKL Ligand Inhibitors (Monoclonal Antibody)

Answer 2

Mech: RANKL is released by bone marrow cells and osteoblasts and binds to the RANK receptor on osteoclasts. This promotes osteoclastic differentiation and activity. Monoclonal antibodies to RANKL can bind to RANKL and make it unavailable to bind its receptor.

Denosumab (Xgeva and Prolia)

Question 3

Angiogenesis Inhibitors

Answer 3

Mech: Bind to VEGF-A preventing it from binding the VEGFR-2 receptor. This leads to anti-angiogenic effects.

Bevacizumab

Question 4

Alkylating Agents

Answer 4

Mech: Damage DNA, impairs DNA replication and transcription = cell death.

Can cause oral mucosal alteration, sterility, GI disturbances, and acute non-lymphocytic leukemia. Highly immunosuppressive.

Cisplatin
Oxaliplatin

Have neurotoxicity associated with their use. Causes cold induced peri-oral paresthesias.

Question 5

Antimetabolites

Answer 5

Mech: Interfere with DNA and RNA growth by substituting
for or competing with the normal building blocks of DNA and RNA. May either inhibit the synthesis of normal nucleotides or compete with them in the formation of DNA or RNA.

S-Phase Specific (DNA Replication)

Inhibit rapidly dividing cells and can cause oral mucositis.

Folate antagonists: methotrexate, premetrexed
Pyrimidine antagonists: 5-florouracil, cytarabine, gemcitabine
Purine antagonists: mercaptopurine, fludarabine

Question 6

Cytotoxic Antibiotics

Answer 6

Mech: Bind to and break DNA inside of cancer cells to keep them from growing and multiplying.

Associated with oral mucositis. Anthracyclines are CARDIOTOXIC and cause tachycardia, arrhythmias, hypotension, CHF, and dyspnea.

Anthracyclines: doxorubicin, daunorubicin, epirubicin, idarubicin

Bleomycin
Plicamycin
Mitomycin

Question 7

Mitotic Inhibitors

Answer 7

Mech: Work in M-phase to prevent cell division.

Vinca Alkaloid Mech: bind β tubulin & block its polymerization with α tubulin into microtubules arresting cells in metaphase and eventually causing apoptosis.

Cause peripheral neuropathy (tingling, numbness, and burning sensations that mimic toothaches)

Vinca Alkaloids: Vincristine and Vinblastine
Taxanes: Paclitaxel and Docetaxel

Question 8

Topoisomerase Inhibitors

Answer 8

Mech: Interfere with topoisomerase which is responsible for unwinding double stranded DNA during replication.

Side effects: primarily GI disturbances but also oral mucositis and myelosuppression (Red, White, and Plarlets) in the bone marrow.

Epipodophyllotoxins: Etoposide
Camptothecins: Irinotecan and topotecan

Question 9

T-cell Inhibitors

Answer 9

Mech: Inhibit helper and killer T-cell activation.

To prevent and treat rejection of organ and bone marrow transplants; RA; Psoriasis.

Cyclosporine (Sandimmune)
Tacrolimus (Prograf; FK506)
Sirolimus (Rapamune)
Everolimus (Zortress)

Question 10

T-cell and B-cell Inhibitors

Answer 10

Mech: Inhibit purine (azathioprine and mycophenolate) and pyrimidine (leflunomide) nucleotide synthesis for lymphocyte
production (T and B).

Azathioprine (Imuran)
Leflunomide (Arava)
Mycophenolate (Cellcept)

Question 11

Corticosteroids

Answer 11

Mech: Complex, involves Hypothalamus, anterior Pituitary, and
Adrenals – known as HPA axis.

Prednisone
Dexamethasone
Prednisolone