Week 6 Drugs

Question 1

Cisplatin

Answer 1

MOA: Chloride ligands, forming positively charged platinum complexes, they bind to specific DNA base sequences, producing intrastrand and interstrand DNA cross-links which are thought to inhibit DNA replication, transcription, and ultimately cell division. Triggers apoptosis.

Side effects: Nephrotoxicity (always support w/ hydration)

Question 2

Methotrexate

Answer 2

MOA: inhibits DNA and RNA synthesis by inhibiting DHFR, blocks purine synthesis

Side effects: Hepatoxicity and Bone marrow suppression.
Nephrotoxicity: especially with cotreatment with other antineoplastics (support with hydration, alkinalizaing urine, leucovorin, and also carpidase when MTX toxicicity is evident)

Question 3

Melphan

Answer 3

MOA: alkylating agent, inhibits DNA and RNA synthesis

Given Orally –> activating in liver

Question 4

Cyclophosphamide

Answer 4

MOA: alkylating agent that prevents cell division by cross-linking DNA strands and decreasing DNA synthesis; cell cycle phase nonspecific agent

Alkylated guanine → cross-linking between strands → prevents DNA replication → p53 activation → cell death

Given orally –> activated in liver to acroleint (non-active agent that causes hemorrhagic cystitis) and phosphoramide mustard (mustard from mustard gas)

Question 5

Etoposide

Answer 5

MOA: topoisomerase II inhibitor. Causes strand breaks. Arrests cells in late S or early G2 phase.

remember = top in Etoposide is for topoisomerase

Question 6

ifosfamide

Answer 6

MOA: causes cross-linking of strands of DNA by binding with nucleic acids and other intracellular structures; inhibits protein synthesis and DNA synthesis

Question 7

fludarabine:

Answer 7

MOA: inhibits DNA synthesis by inhibition of DNA polymerase and ribonucleotide reductase; also inhibits DNA primase and DNA ligase I

Question 8

ara-C

Answer 8

MOA: Competitively inhibits DNA polymerase-α and DNA polymerase-β, thereby resulting in blockade of DNA synthesis and DNA repair. Incorporated into DNA and RNA.

Question 9

busulfan

Answer 9

MOA: alkylating agent which interferes with DNA replication and transcription of RNA. Interferes with the normal function of DNA by alkylation and cross-linking the strands of DNA.

Question 10

Doxorubicin

Answer 10

MOA:Anthracycline antibiotic: DNA intercalating agent

• Inhibition of DNA Replication/Transcription (M phase)
• Intercalates at points of supercoiling
• Inhibitor of Topo II
• Iron chelator
• Iron-doxorubicin complex binds DNA and produces free radicals

Question 11

5-Fluorouracil

Answer 11

MOA: Prevents synthesis of thymidine triphosphate
Inhibits DNA replication
Antimetabolite (S phase)

Question 12

Paclitaxel

Answer 12

MOA: Mitotic spindle poison

• High-affinity binding to microtubules with enhancement of tubulin polymerization
• M phase
• Inhibition of mitosis and cell division

Question 13

Mesna

Answer 13

MOA: Uroprotective agent - a synthetic sulfhydryl (thiol) compound that binds acrolein. Exhibits detoxification activity in urinary tract only; does not appear to alter systemic activity or nonurologic toxicity of oxazaphosphorine derivatives (e.g., ifosfamide, cyclophosphamide).

not cell cycle specific

Used with cyclophosphamide/isofosphamide

Question 14

Granulocyte Colony Stimulating Factor

Answer 14

MOA: Bone marrow Stimulating factor.

Question 15

Glucarpidase

Answer 15

MOA:Enzyme used to treat methotrexate toxicities. Converts MTX into inert metabolite.

Question 16

Leucovorin

Answer 16

Folicinic acid that is readily converted to other folic acid derivatives such as THF. Specific for healthy cells, cancer cells can’t uptake folinic acid well.

Use with methotrexate toxicity.

Question 17

Methotrexate (Rheumatrix)

Answer 17

MOA: Blocks DHFR preventing nucleotide synthesis. This prevents B and T cell proliferation needed for RA

Take a folate supplement?

DMARD

Question 18

Hydroxychloroquine

Answer 18

Prevents acidification of macrophage cytosol. Likely major site of action is TLR 9. This prevents the upregulation of cytokine release.

Question 19

Leflunomide (Arava)

Answer 19

Inhibits pyrimidine synthesis by blocking oronate pathway. Primarily T cells and potentially B cells.

Question 20

Sulfasalzine

Answer 20

Metabolized in colon to active sulfapyridine and 5-amino-salicylic acid.

Sulfapyridine - free radical scavanger
5 amino-salicylic acid is a COX inhibitor.

Not well absorbed in gut but an effective alternative to MTX or hydroxychloroquine

Toxicity: - Rash, neutropenia and myelosuppression.

Question 21

Gold

Answer 21

MOA: suppresses phagocytosis by macrophages. Can also suppress T cells. Unclear MOA

Least tolerated (rheumatoligist said we no longer use this)

Question 22

Azathioprine

Answer 22

MOA: Purine analog that block DNA synthesis. Primary action is T cells.

Question 23

Cyclosporine

Answer 23

MOA: Immunosuppresent used to control transplant rejection that works via inhibition of calcineurin. Major arthritis action site is T cells.

Adverse effects - renal disruption (ironic because we gave it for transplants am I right?)

Question 24

Etanercept and Infliximab

Answer 24

MOA: TNF alpha inhibitors.

Adverse effects - immunosuppressants (screen for TB)

Question 25

Anakinra

Answer 25

Interleukin 1 receptor antagonist. Infrequently used.

Question 26

Rituximab

Answer 26

binds CD 20 on B cells suppressing their activity

Question 27

Abatacept

Answer 27

Binds to CD 80 on T cell preventing activation.