Alkylating Drugs General Info Flashcards
(47 cards)
What 2 groups of drugs act on DNA?
- how do these groups differ?
Antimetabolites:
- Inhibit DNA synthesis
Alkylating Agents:
- Damage DNA structure
How does overall goal of cancer treatment changed in the recent years?
Older Drugs:
- Targeted proliferating cells and are toxic
Newer Drugs:
- Target growth of the cancer cell
**The newer drugs are insanely expensive
What tissues are most affected by chemotherapy?
- Blood and Bone Marrow
- Epithelial Lining of the oral cavity
- Gastrointestinal tract
- Growing hair
Dose dependent nausea and vomiting is a common side effect of chemotherapy.
- explain the 2 different processes that cause this effect.
- CHEMOTRIGGER zone in the base of the 4th ventricle in the GI tract
- Psychological Aspects of Impending therapy can also cause this
What is the difference between adjuvant and neoadjuvant therapy?
Adjuvant Therapy:
- Given After Surgery or Radiation
Neo-aduvant Therapy:
- Given Before surgery or Radiation
When are the following use:
- Surgery
- Radiation
- Chemotherapy
Surgery:
- Solid tumor can be cut out
Radiation:
- Tumors in difficult to reach locations
Chemotherapy:
- Best option in blood cancers and metastases, can be just as adjuvant or neo-adjuvant
What is biological therapy?
- when can it be used?
Biological Therapy:
- Targeted approach using mAbs etc.
Only can be used if patient is positive for the epitope that the drug targets
In addition to their affects on rapidly dividing cell populations, what are some of the toxicities caused by anti-cancer drugs?
- Secondary Malignancies
- Organ Toxicity
- Sterility
How and why do we measure a patients response to a drug?
How:
- CT, PET, MRI
- Tumor Markers
- Quality of Life Improvement
Why:
- We want to justify use of a particular drug showing that it will increase life-span or make life for cancer patients more tolerable.
What is Tumor Lysis Syndrome (TLS)?
- what type of cancers does this occur with?
Large Tumors may lyse quickly releasing their contents into the bloodstream
4 Main Downstream Effects:
• Volume Depletion and Obstruction of Renal Tubules with Debris
• Purine Nucleotides, Potassium, and Proteins reach high conc. in blood
• Uric acid may be deposited causing Gout
How do we manage the effects of TLS?
Management:
- Hydration
- Acid/Base Correction
- BICARB to ALKALINIZE the urine
- DRUGS that prevent PRECIPITATION
What compound are we most worried about precipitating out in the kidneys?
- what drugs can we give to prevent this?
- how do they work?
- method of administration?
Uric Acid Crystals
Allopurinol (PO) works on Xanthine Oxidase to PREVENT formation of uric acid
Rasburicase (IV) works on Urate Oxidase to convert uric acid that is formed into Allantoin
What is the difference between a chemotherapy drug that is cell cycle phase specific and one that is not?
Cell Cycle Phase Specific drugs will only work on a fraction of the cells in a tumor that happen to be in that cell cycle phase while the drug is being administered
Non-specific drugs will work on cells in any part of the cell cycle
NOTE:
1) not every chemo drug can be used against every type of tumor
2) Small structural changes in drug can greatly change the spectrum of antitumor activity
NOTE:
1) not every chemo drug can be used against every type of tumor
2) Small structural changes in drug can greatly change the spectrum of antitumor activity
What are the 3 general Groups of Alkylating agents?
- how do their structures differ?
Chloroacetaldehydes (O=CH2CH2-Cl) :
- Bis(chloroethyl)amines (2 of these groups)
- Nitrosoureas
Alkylsulfonate (OSO2Me)
Is Cyclophosphamide a biologically active agent?
- if not what is needed for its activation?
- where is this done?
- What affect does it have on this tissue?
No it must first be converted to an active agent in the liver by CYP2B.
- active agent exists in an equilibrium with between 2 active forms (cyclic and non-cyclic)
*This is done in the liver and the liver itself is protected because the active compound is inactivaed to a 4-keto product
What 2 toxic agents are the actived products of cyclophosphamide turned into?
- Acrolein
2. Phosphoramide Mustard
What is the general method used by the Bis(chloroethyl)amine alkylating agents to mess up DNA?
- what is their target?
- Different possibilities?
- NAME THESE AGENTS
Target:
- N7 GUANINE is the MAIN target (most approachable)
Possibilities:
- 2 moieties on each of the alkylating agents once the first alkylation has been performed the second group is free to produce:
a. Intrastrand Linkage
b. DNA cross-linking with the complementary strand
AGENTS: • Cyclophosphamide • Ifosfamide • Mechlorethamine • Melphalan
When are the Bis(chloroethyl)amine alkylating agents effective?
- To what cell populations are these drugs most toxic?
- NAME THESE AGENTS.
Late G1-S is when cells are the MOST susceptible causes a G2 BLOCK - AGENTS: • Cyclophosphamide • Ifosfamide • Mechlorethamine • Melphalan
What are some of the adverse affects of Bis(chloroethyl)amine alkylating agents?
- NAME THESE AGENTS.
HEMORRAHAGIC CYSTITIS (give mesna to counter effect) and Renal Failure
- Cyclophosphamide
- Ifosfamide
Pulmonary Fiborsis
- Cyclophosphamide
- Melphalan
Significant Vesicant Action
- Mechlorethamine
Rapid onset Congestive Heart Failure
- Cyclophosphamid
CNS - altered Mental Status, Seizures, Coma
- Ifosfamide
What are some of the long term toxicities associated with ALL alkylating agents?
- which of these show these adverse effects more frequently?
Lung Problems:
- Fibrosis, Cynaosis
2˚ Cancers:
- Leukemias and Solid Tumors
Teratogenicity:
- 1/6 have malformed offspring
What drug is given to try to reduce the hemmorhagic cystitis produced by Ifosfamide and Cyclophosphamide?
- How is this drug administered?
- what is the by product of the Bis(chloroethyl)amines that causes this symptom?
Acrolein (one of the cytotoxic metabolites of the activative Bis(choroetyl)amines) causes the damage (more common of a side effect with ifosfamide)
MESNA
- along with good hydration this prevents Hemmorhagic Cystitis
- Given IV or PO
How do we keep Mesna from concentrating in the tumor and neutralizing acrolein that acts on the tumor cell?
Its concentrated in the kidney and bladder so it will likely avoid the cancer
Besides being used for cancer what are two other uses for Cyclophosphamide?
- prepare pts. for Stem Cell Transplants
2. Rheumatoid Arthritis (last resort)
