Pharmacology: Antineoplastics I - 1

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What are the Nitrogen Mustards?
- Mechlorethamine (Mustargen)
- chlorambucil (Leukeran)
- melphalan (Alkeran)
- Cyclophosphamide (Cytoxan)
- Ifosfamide (Ifex))
Which Nitrogen Mustards are Alkylating agents?

All
How is Mechlorethamine (Mustargen) administered?
- IV
- NEVER ORAL
What are the SE for Mechlorethamine (Mustargen)?
- Vesicant
- Unstable
What are the indications for Mechlorethamine (Mustargen)?

Hodgekin’s and non-hodgekin’s lymphoma
What is the route of administration for chlorambucil (Leukeran)?

Oral
How does chlorambucil (Leukeran) Compare to Mechlorethamine (Mustargen)?
- chlorambucil (Leukeran) is:
- Slower acting
- Less toxic
- Longer half life
- Orally acting
How does chlorambucil (Leukeran) Compare to other Nitrogen Mustards?

Least toxic and slowest acting
Melphalan (Alkeran) is given by what route?

Oral
Is Melphalan (Alkeran) effective against Melanomas?

No
What is unique about the structure of Melphalan (Alkeran)?

Contains a phenylalanine = Adds stability
What is Melphalan (Alkeran) used to treat?

Myeloma, Breast and ovarian cancer
How do cyclophosphamide (Cytoxan) and ifosfamide (Ifex) compare to other Nitrogen mustards?

Used more frequently = High priority drugs
What is the route of administration for Cyclophosphamide (Cytoxan)?

IV or oral
What is the route of administration for ifosfamide (Ifex)?
- Only IV
- Oral causes neurotoxicity due to a metabolite produced by the stomach
Which drug is the most useful and versatile of the mustards?

ifosfamide (Ifex)
Do Cyclophosphamide (Cytoxan) and Ifosfamide (Ifex) have short or long half lives?

Releatively long (7 hours)
Are Cyclophosphamide (Cytoxan) and Ifosfamide (Ifex) active or prodrugs?

Prodrugs: require activation in the liver by CYPs
What is the toxic metabolite produced from break down of Cyclophosphamide (Cytoxan) and Ifosfamide (Ifex) and what does it do?

Acrolein: causes hemorrhagic cystitis = bladder bleeding
What are the general side effects of all Nitrogen Mustards?
- Bone marrow depression
- GI: N/V
- Alopecia
- Hemorrhagic cystitis (just Cyclophosphamidea and Ifosfamide)
- Amenorrhea
- Immunosuppression
- Secondary acute leukemias
Cyclophosphamide causes what side effects more than other Nitrogen Mustards?
- Hemorrhagic cystitis (only caused by Cyclophosphamidea and Ifosfamide)
- Immunosupression
Ifosfamide causes what side effects more than other Nitrogen Mustards?
- Hemorrhagic cystitis
- (only caused by Cyclophosphamidea and Ifosfamide)
What can be done to treat hemorrhagic cystitis caused by Nitrogen Mustards?
- Give: N-acetyl-cysteine or mesna
- Inactivates toxic metabolites
- Requires extensive hydration
Ifosfomide comes only as a combination, what drug is it supplied with?

Mesna = to reduce Hemorrhagic cystitis
Cyclophosphamide would be used a lower (than cancer) dose, for what purpose?

As an immunosuppressant
Which Nitrogen Mustard might be used to treat rheumatoid arthritis?

Cyclophosphamide (due to its immunosuppressant capabilities)
Which Nitrogen Mustard has very rapid action and a short half-life?

Mechlorethamine
All Nitrogen Mustards have acute side effects of Nausea and Vomiting, which one also has acute myelospuression?

Mechlorethamine
The delayed side effects of which two Nitrogen Mustards are Myelosupression and risk of AML?
- Melphalan
- Chlorambucil
What are the delayed side effects of Mechlorethamine?
- Reproductive organ inhibition
- Teratogenicity
What are the delayed side effects of Ifosfamide and Cyclophosphamide?
- Myelosuppression
- Hemorrhagic cystitis
- Alopecia
- Amenorrhea
- Sterility
What is the route of administration for Bisulfan?

Oral or IV
What difference in SE do you see with Bisulfan between high and low doses?
Low doses: Only inhibit WBCs
- High Doses: Kills bone marrow = Inhibits platelets, WBCs and
- RBCs

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Pharmacology: Antineoplastics I - 1

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Pharmacology: Antineoplastics I - 1

Updated

2014-04-18T16:56:41Z