Anti-Cancer Drugs Flashcards
(23 cards)
Criteria for drugs used in combination tx
- Each drug should be active alone against the particular cancer
- The drugs should have different targets/mechanisms of action
- Cross-resistance between drugs should be minimal
- The drugs should have different toxicities to the patient
Recruitment tx
initial use of CCNS drug resulting in recruitment of previously resting cells into active cell division, where they are now susceptible to a CCS drug
Name the classes of anti-cancer drugs
- DNA-damaging drugs (CCNS)
- Antimetabolites (CCS)
- Antimitotic agents (CCS)
- Topoisomerase inhibitors (CCS)
- Hormonal Agents (Prednisone)
- Target-specific agents
DNA-damaging drugs
- General
- List drugs
- CCNS
-Alkylating agents
-Platinum compounds
-Antitumor antibiotics
-Cause DNA cross-linking, abnormal base pairing, strand breaks - Drugs:
- Bleomycin
- Carboplatin
- Doxorubicin
Antimetabolites
- General
- List drugs
- CCS
-Act mainly S phase
-Structurally similar to purines and pyrimidines required for nucleic acid biosynthesis, interfere with DNA synthesis - Drugs:
- 5-Fluorouracil
- Gemcitabine
- Methotrexate
Antimitotic agents
- General
- List drugs
- CCS
-“Spindle poisons”
-interfere with microtubule function
-act mainly in M phase - Drugs:
- Vincristine
- Paclitaxel
Topoisomerase Inhibitors
- General
- List drugs
- CCS
- Drugs:
- Etoposide
- Irinotecan
Target-Specific agents
- What types of drugs fall into this category?
-Monoclonal antibodies
-mTOR inhibitors
-Tyrosine kinase inhibitors
Target-Specific agents:
1. Monoclonal antibodies
Bevacizumab
Cetuximab
Rituximab
Trastuzumab
Target-Specific agents:
2. mTOR inhibitors
Temsirolimus
Target-Specific agents:
- Tyrosine kinase inhibitors
Erlotinib
Imantinib
Sunitinib
Common adverse effects of anticancer agents:
Immediate
- Hours to days
a) Nausea, vomiting, abdominal pain, anorexia
b) Allergic, hypersensitivity reactions
• a lot with chimeric Ab or natural products by fungi or other organisms
c) Local necrosis (extravasation)
Common adverse effects of anticancer agents:
Early
- Days to weeks
a) Impaired wound healing
b) Myelosuppression: leukopenia, neutropenia, anemia, thrombocytopenia
c) Mucositis
• inflammation and ulceration of the digestive tract
d) Diarrhea
• usually symptom of mucositis
e) Alopecia
Common adverse effects of anticancer agents:
Delayed
- Weeks to months
a) Aspermia
b) pulmonary fibrosis
c) Neurotoxicity
- often w/spindle poisons
Common adverse effects of anticancer agents:
Late
- Months to years
- sterility
- secondary malignancies (5-7 years)
General precautions when using anticancer agents
1. Baseline and periodic CBCs
2. Active infections; watch for opportunistic infections e.g.
Pneumocystis pneumonia
3. Avoid patient dehydration; aggressive hydration (~ 3 mL/kg/hr) with NS is usually beneficial
4. Avoid vaccination during therapy because of reduced immune response
- Health care personnel should avoid accidental exposure during preparation and handling, use protective gowns, gloves, goggles
- Avoid extravasation!
- Pregnancy Risk Category D or X
DNA-damaging drugs: Alkylating agents:
General mech and List drugs
- Nitrogen mustards alkylate DNA causing cross-linkages
- Cyclophosphamide
Temozolomide
Platinum Compound Drug
Carboplatin (paraplatin)
Antitumor Antibiotics
Bleomycin
Doxorubicin
Monoclonal Abs
General Mechanism
- Artificially produced, designed to bind to antigens expressed on the surface of malignant cells
a) Block the growth of cancer cells and/or recruit the body’s immune system to attack the cancer cells
c) Can be given as monotherapy, in combination with chemotherapy, and with other targeted therapies under clinical trial
Common Infusions Reactions to mouse antigen
fever chills NV hypotension angioedema bronchospasm
Tyrosine Kinase Inhibitors: General
- TK in cancers become constitutively activated leading to unrestricted cell growth
- All of these drugs are CYP3A4 substrates so a lot of drug interactions can happen!
Mechanisms of resistance to anticancer treatment
1. Increased DNA repair a) Alkylating agents b) Platinum compounds 2. Increased inactivation a) Increased GSH production → trapping of electrophilic drugs --Bleomycin --Platinum compounds --Anthracyclines (doxorubicin) b) Increased enzymatic inactivation
- Target or suppressor mutations
a) DHFR overexpression (methotrexate)
b) Topoisomerase mutations (etoposide, irinotecan)
c) Mutation in p53 tumor suppressor gene → decreased apoptosis - Decreased activation of prodrugs
a) Purine and pyrimidine antimetabolites - Decreased drug accumulation
a) Increased efflux via P-glycoprotein (ABCB1; MDR1)
