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P & T I Block 1 > Antineoplastics > Flashcards

Antineoplastics Flashcards

1
Q

Fill in the blank

A

Antimetabolites

drugs in this class include:

Azathioprine

Cladbirine

Cytarabine

5-FU

Hydroxyurea

Methotrexate

6-mercaptourine

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2
Q

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A

Topoisomerase inhibitors

drugs in this class inlude:

  • “poside” drugs and - “tecan” drugs

Etoposide

Teniposide

Irinotecan

Topotecan

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3
Q

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A

Bleomycin- works in the G2 phase and causes double stranded breaks in dna (recall the blue whale thing from sketchy pharm)

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4
Q

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A

Microtubule inhibitors: Vinka alkaloids and taxanes

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5
Q

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A

Cell cycle independent/non specific agents: alkyating agents, platinum agents (e.g. cisplatin)

Steroids/Asparganase

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6
Q

Alkylating agents are cell cycle (specific/non-specific) cancer drugs and the classes of alkylating agents include ___ (e.g. cyclophosphamide), alkyl sufonates, ___ and nitrosureas

A

Alkylating agents are cell cycle (specific/non-specific) cancer drugs and the classes of alkylating agents include nitrogen mustards (e.g. cyclophosphamide), alkyl sufonates, platinum agents/analogues and nitrosureas (she didn’t teach these but know that these are drugs that end in -ustine e.g. carmustine and you need to know these for Step 1)

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7
Q

The nitrogen mustards ___ and ___ are converted into the active compound phospharamide mustard by the liver and work by crosslinking dna at guanine

A

The nitrogen mustards cyclophosphoramide and ifosfamide are converted into the active compound phospharamide mustard by the liver and work by crosslinking dna at guanine

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8
Q

Nitrogen mustards can cause toxicity via the toxic metabolite ___

List the adverse effects of nitrogen mustards

A

Nitrogen mustards can cause toxicity via the toxic metabolite acrolein

Adverse effects:

myelosuppression

hemorrhagic cystitis

bladder toxicity

SIADH

Fanconi syndrome

(Ifosfamide causes neurotoxicity)

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9
Q

Nitrogen mustards are used for a variety of cancers, including solid tumors, __, ___ and even rheumatic disease

A

Nitrogen mustards are used for a variety of cancers, including solid tumors, leukemia, lymphoma and even rheumatic disease

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10
Q

The acrolein toxic metabolite from nitrogen mustards can cause bladder toxicity. To prevent this, hydration and ___ are used

A

The acrolein toxic metabolite from nitrogen mustards can cause bladder toxicity. To prevent this, hydration and mesna are used

(mesna binds to metabolites in the bladder and detoxifies/inactivates them

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11
Q

Ifosfamide causes neutroxicity through which mechanism? How does encephalopathy caused by ifosfamide manifest?

A

Ifosfamide causes neurotoxicity via chloroacetaldehyde (toxic metabolite) crossing the blood brain barrier

Encephalopathy manifests as cerebellar ataxia at infusion or shortly thereafter, visual hallucinations, confusion

**neurotoxicity can be stopped by stopping the medication or using methylene blue? or not using meds that have CNS effects**

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12
Q

___ is an alkylsufonate used to ablate a patient’s bone marrow prior to hematopoietic stem cell transplant, esp for leukemia

A

Busulfan is an alkylsufonate used to ablate a patient’s bone marrow prior to hematopoietic stem cell transplant

MOA: dna crosslinking

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13
Q

The side effects of busulfan include severe ___ (in the blood), pulmonary fibrosis, ____ (both the negros could use some) and hepatotoxicity

A

The side effects of busulfan include severe myelosuppression (in the blood), pulmonary fibrosis, hyperpigmentation (both the negros could use some) and hepatotoxicity

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14
Q

The drugs in the platinum class include cisplatin, ___ and ___. Platinum agents are generally used in ___ tumors

A

The drugs in the platinum class include cisplatin, carboplatin and oxaliplatin. Platinum agents are generally used in solid/epithelial tumors

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15
Q

As a class, platinum agents cause ___.

Fill in the table below

A

As a class, platinum agents cause peripheral neuropathy (can be managed with neuropathic pain medication)

**note that platinums work by cross-linking DNA and you need to use amifostine to prevent peripheral neuropathy caused by these drugs**

**also know that they’re predominantly used in gynecologic cancers (so testicular and ovarian cancers), bladder cancer, GI and lung carcinomas**

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16
Q

The antimetabolite drugs include drugs from which classes?

A

Purine antagonists (6-MP and Azathioprine)

Pyrimidine antagonists (Cytabarine, Gemcitabine, Capecitabine, 5-FU)

Folate antagonists (Methotrexate)

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17
Q

Fill in the blanks

A
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18
Q

___ is a cancer drug that can also be used to treat sickle cell anemia

The major adverse effect of this drug is ___

A

Hydroxyurea is a cancer drug that can also be used to treat sickle cell anemia. Used in myeloproliferative disorders such as CML and polycythemia vera

The major adverse effect of this drug is severe myelosuppression

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19
Q

What is the mechanism of action of hydroxyurea?

A

Hydroxyurea inhibits ribonucleotide reductase >> prevents formation of de-UDP from UDP >> inhibits dna synthesis

20
Q

___ is a prodrug of 6-MP. 6-MP can be converted to 6-methymercaptourine by ___

A

Azathoprine is a prodrug of 6-MP. 6-MP can be converted to 6-methymercaptourine by TPMT

21
Q

What is the downstream effect of a homozygous deficient mutation in TPMT?

6-MP and Azathioprine have drug interactions with allopurinol. Explain this interaction.

A

Patients that are homozygous-deficient in TPMT have excess accumulation of 6-MP (recall from sketchy that 6-MP is the active drug, converted from the pro-drug azathioprine)

Both azathioprine and 6-M are metabolized by xanthine oxidase. Since allopurinol (which you will recall is a drug given to treat tumor lysis syndrome) inhibits xanthine oxidase, taking allopurinol concurrently with 6-MP/azathioprine causes increased levels of these drugs

22
Q

The main adverse effects of purine antagonists (6-MP and azathioprine) are ___, GI and liver toxicity

These drugs are mainly used for ___ and ___

What is the mechanism of action of these drugs?

A

The main adverse effects of purine antagonists (6-MP and azathioprine) are myelosuppression, GI and liver toxicity

These drugs are mainly used for leukemia and prevention of solid organ transplant rejection

MOA of purine antagonists: 6-MP inhibits PRPP amidotransferase >> no IMP production from PRPP

also inhibits IMP conversion to AMP and GMP >> no dna synthesis

23
Q

Examples of pyrimidine antagonists/analogs include ___, ___ (an oral prodrug of 5-FU) and ___

A

Examples of pyrimidine antagonists/analogs include 5-fluorouracil (5-FU), Capecitabine (an oral prodrug of 5-FU) and Cytarabine

24
Q

5FU and Capecitabine are primarily used in ___ cancers

The primary adverse effects of 5FU are __ and ___

The effects of 5FU are enhanced with the addition of which drug?

A

5FU and Capecitabine are primarily used in GI and GU cancers

The primary adverse effects of 5FU are myelosuppression and palmar-plantar erythodysethesia (hand foot syndrome)

The effects of 5FU are enhanced with the addition of Leucovorin

**the F in 5FU is for the foot in hand-foot-syndrome**

25
Q

Describe the MOA of 5FU

Patients with a genetic defect in ___ can accumulate toxic levels of 5FU. If you are concerned about 5FU toxicity, what would you give to treat this?

A

MOA of 5FU - 5FU converted to 5-Fd-UMP which binds thymidylate synthase >> blocks conversion of dUMP to dTMP >> decreases DNA synthesis

Patients with a genetic defect in dihydropyrimidine dehydrogenase (DPD) can accumulate toxic levels of 5FU

**emergency antidote for 5FU toxicity = uridine triacetate**

26
Q

Cytarabine is primarily used for which types of cancer?

High dose cytarabine (__ or more) can cross the blood brain barrier and potentially cause what unique side effects?

A

Cytarabine (AraC) is primarily used for leukemia and lymphoma

High dose cytarabine, >1000mg/m2 (or 1 gram) or more can cross the blood brain barrier and cause cerebellar neurotoxicity (AraCNS) and chemical conjunctivitis (AraSEE)

27
Q

How would you treat chemical conjunctivitis caused by cytarabine?

A

Use steroid eye drops

28
Q

Describe the mechanism of action of methotrexate

What is the function of leucovorin when given with methotrexate?

A

MTX inhibits dihydrofolate reductase >> no conversion of dUMP to dTMP >> no dna synthesis

Leucovorin works to “rescue” normal cells from the cytotoxic effects of MTX

29
Q

MTX is generally used to treat what kinds of cancers?

MTX is one of two drugs, (___) as well, that can be given intrathecally

High dose MTX can cross the BBB and cause which side effects?

A

MTX used to treat leukemias (ALL), lymphomas, choriocarcinoma and sarcomas

MTX and cytarabine can be given intrathecally

High dose MTX can lead to myelosuppresion, mucositis, acute kidney injury, hepatotoxicity, pulmonary fibrosis, encephalopathy, folate deficiency

30
Q

Name 3 ways you could prevent MTX toxicity

A

Leucovorin rescue

Urine alkalinization (MTX accumulates in the urine/forms uric acid crystals at acidic pH)

Hydration

**there’s also an antidote - glucarpidase**

31
Q

___ is a Topoisomerase I inhibitor used to treat GI and GU cancers

A

Irinotecan (I ran to the can)

32
Q

Irinotecan is metabolized by ___ via glucuronidation >> water soluble metabolites >> excretion

Patients with a deficiency in ___ have toxic levels of irinotecan. Toxicities of irinotecan include ___ and ___ (recall I ran to the can)

A

Irinotecan is metabolized by UGT1A1 via glucuronidation >> water soluble metabolites >> excretion

Patients with a deficiency in UGT1A1 have toxic levels of irinotecan. Toxicities of irinotecan include severe myelosuppression and diarrhea (recall I ran to the can)

** early diarrhea remedied with atropine, late remedied with loperamide**

33
Q

Describe the mechanism of action of anthracyclines. Which drugs are in this class?

Which enzyme do these drugs inhibit?

A

Anthracyclines intercalate in dna >> free radicals >> dna strand breaks >> decreased dna replication

Drugs in this class: daurubicin, daxorubicin, idarubicin (so anything that ends in -rubicin- )

These guys are topo II inhibitors

34
Q

Daxorubicin and daurubicin are predominantly used for what kinds of cancers?

The main adverse effects of anthracyclines are ___ (manifesting as dilated cardiomyopathy), myelosuppression and alopecia

A

Clinical uses of anthracyclines: solid tumors, leukemia, lymphoma

Toxicities: cardiotoxicity (manifests as dilated cardiomyopathy/congestive heart failure), myelosuppression and alopecia

35
Q

___ is an anti-tumor antibiotic used primarily for testicular cancer and Hodgkin’s lymphoma

A

Bleomycin is an anti-tumor antibiotic used primarily for testicular cancer and Hodgkin’s lymphoma

36
Q

Bleomycin toxicities include ___ and ___

A

Bleomycin toxicities include pulmonary fibrosis and skin hyperpigmentation

37
Q

Describe the MOA of vinca alkaloids. Which drugs are in this class?

A

Vinca alkaloids (Vinblastine and Vincristine) inhibit microtubule formation

38
Q

What are the side effects of vinca alkaloids?

Vinca alkaloids are indicated for solid tumors, as well as ___ and ___

A

Vinblastine “blasts” the bone marrow - myelosuppression

Vicristine causes sensory and motor neuropathy

Vinca alkaloids are indicated for solid tumors, as well as leukemia and lymphoma

39
Q

___ are also a group of microtubule inhibitors that work by preventing anaphase

Name the drugs that are in this class

A

Taxanes

Drugs in this class: -taxel- drugs >> paclitaxel, docetaxel

40
Q

What are the side effects of taxanes as a class and individually?

A

As a class: peripheral neuropathy, myelosuppression

Paclitaxel: hypersensitivity reactions

Docetaxel: skin and nail changes + fluid retention

41
Q

___ are a class of cancer drugs that induce arrest at G2-M phase and apoptosis and include bortezomib, ___ and ___

Which 2 types of cancer are these used for?

A

Proteasome inhibitors ( - zomibs) are a class of cancer drugs that induce arrest at G2-M phase and apoptosis and include bortezomib, carfizomib and ixazomib

Used for multiple myeloma and mantle cell lymphoma

42
Q

The side effects of proteasome inhibitors include peripheral neuropathy and ___ (you learned about this zoster thing last block)

A

Side effects of proteasome inhibitors include thrombocytopenia, cardiomyopathy, herpes zoster reactivation, peripheral neuropathy

43
Q

Tamoxifen is a ___ modulator

A

Tamoxifen is a selective estrogen receptor modulators (SERMs)

44
Q

The aromatase inhibitors include ___ (3) (hint: drugs ending in -ozole)

A

Aromatase inhibitors include letrozole, anastrozole, exemstane

45
Q

Adverse events of tamoxifen include:

A

Menopausal symptoms and risk of venous thromboembolism

46
Q

Aromatase inhibitors can cause __

A

Arthralgias, myalgias, and risk of bone fractures

P & T I Block 1 (11 decks)

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