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Spring Pharm > Chemo > Flashcards

Chemo Flashcards

1
Q

Alkylating Agents

A

Nitrogen Mustards (Cyclophosphamide/Cytoxan)

Nitrosureas (Carmustine)

Platinum Compounds (Cisplatin/Carboplatin)

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2
Q

Alkylating Platinum Compounds:

MOA:

A

Alkylating Platinum Compounds:

MOA: Do not have an alkyl group, cross link guanine bases in DNA with different structural elements (platinum atom, two amines, two chlorides)

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3
Q

Alkylating Agents

toxicities:

A

Alkylating Agents

toxicities:

  1. Bone Marrow Suppression
  • biggest concern
  • neutropenia, hemolytic aneima, thrombocytopenia
  1. Mucositis
    * worry with airway manipulation/instrumentation

3. Skeletal Muscle Weakness

4. Seizures

5. Pneumonitis & Pulm. Fibrosis

  • 1% fibrosis c cyclophosphamide
  • 20-30% carmustine

6. SIADH

7. Uric Acid Nephropathy

8. Impaired Pseudocholinesterase

  • concern with succinylcholine

9. Nephropathy -> CISPLATIN

10. Peripheral Neuropathy -> Oxaliplatin

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4
Q

Carmustine Toxicity

A

Carmustine Toxicity

Pulmonary Toxicity = 20-30%

Mortality = 24-90% similar to bleomycin

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5
Q

Impaired Psuedocholinesterase with alkylating agents

A

Can last 2-3 weeks!

Affects succinylcholine, mivacurium, esmolol, remifentanil

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6
Q

Cisplatin:

  1. Dose Limiting Toxicities
  2. Prevention:
A

Cisplatin:

Dose Limiting Toxicities

Nephropathy:

  • cumulative!
  • dose-limiting
  • Early signs = potassium and magneisum wasting and decrease GFR

To Prevent:

  • Hydration
  • Supplemental electrolytes
  • May be on furosemide and/or mannitol to prevent
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7
Q

Oxiplatin

Dose Limiting Toxicities:

A

Oxiplatin

Dose Limiting Toxicities:

Peripheral Neuropathy

  • Dose-limiting effect.
  • Presents as tingleing around mouth, fingers, toes.
  • Avoid cold contact.
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8
Q

Anti-Metabolite Agents

A

Methotrexate (Folic Acid)

Fluorouracil (Pyrimidine)

Mercaptopurine (Purine)

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9
Q

Methotrexate

MOA:

A

Methotrexate:

MOA: Binds to dihydrofolate reductase, prevents reduction of FH2 to FH2 and prevent synthesis of DNA nucleotides.

Normal pathway of Folate:

Folate -> FH2 -> FH4 by enzyme: dihydrofolate reductase.

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10
Q

Methotrexate

Toxicities

A

Methotrexate

Toxicities

1. Fulminant pumlonary fibrosis,

  • non cardiogenic pulmonary edema
  • 8%

2. Neutropenia & Thrombocytopenia

3. Mucositis & GI ulceration

4. Renal Toxicity (10%)

  • usually permanent

5. Hepatic Toxicity

  • can be reversible
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11
Q

Fluorouracil

MOA:

A

Fluorouracil

MOA:

Inhibits thymidilate synthesase. Which inhibits nucleotide production ->

end result: inhibits DNA synthesis

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12
Q

Fluorouracil

Toxicities:

A

Fluorouracil

Toxicities:

1. Increased risk for MI for 1 week after administration

  • delay surgery if possible
    2. Myelosuppresion
  • leukopenia, thrombocytopenia, anemia
    3. Alopecia
    4. Neurological Defects
  • Ataxia - cerebellum
    5. GI toxicity
  • d/c if stomatitis, mucositis, diarrhea
  • Patients at risk for GI ulceration and perforation
  1. Hand-and-Foot Syndrome
    * tingling, redness, burning, flaking, swelling, blistering of palms and toes
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13
Q

Topoisomerase Inhibitor Agents

A

Anthracyclines: Doxorubicin, Daunorubicin

Non-anthracyclines: Bleomycin

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14
Q

Topoisomerase Inhibitors - Anthracyclines

MOA:

A

Topoisomerase Inhibitors - Anthracyclines

MOA:

Anthracyclines; Doxorubicin, Daunorubicin:

Inhibtion of topoisomerase I and II and intercalation with DNA -> double strand DNA breaks and inhibtion of DNA & RNA synthesis (inhibtion of DNA replication)

Toposiomerase II: relaxes the DNA supercoil and breaks the strand for replication, also crticial to putting the DNA bakc together

-> If you can’t unwind the coil, you can’t replicate the DNA

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15
Q

Topoisomerase Inhibitors - Non-Anthracyclines

MOA:

A

Topoisomerase Inhibitors - Non-Anthracyclines

MOA:

Non-Anthracyclines: Bleomycin

Topoisomerase inhibtion + binds to DNA and chelates iron leading to formation of free radicals that cause single and double strand DNA breaks

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16
Q

Bleomycin

Toxicities

A

Bleomycin

Toxicities

Pulmonary Toxicity

  • (4% -> 1% = “life threatening”)
  • Mechanism: lungs take up high concentrations of drug and lack the enzyme hydrolase to inactivate the bleomycin
  • Increased risk with:
    • cumulative dosing
    • age
    • chest radiation
    • pulmonary co-morbidities
    • oxygen exposure
    • other chemotherapy drugs
    • genetics

May progress from pulmonary fibrosis -> severe fibrosis -> death.

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17
Q

Special Considerations for mangaing SE of bleomycin:

A

Pulmonary Toxicity:

  1. Discontinue at first signs of toxicity: dry cough, dyspnea, tachypnea, infiltrates on CXR
  2. Keep FIO2 concentations at or below 30% during anesthesia if possible.
    1. Titrate SaO2 ~ 90%
    2. Avoiding hyperoxia = avoiding further injury from free radicals
  3. Pre-Op: baseline serial PFTs, CXR, ABG,
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18
Q

Chemotherapy agents that DO NOT cause myelosuppresion

A

Bleomycin

(“very little” = vincristine)

19
Q

Tubulin-Binding Drugs

MOA:

A

Tubulin-Binding Drugs

MOA:

Binds to tubulin (microtubule dimers) to block microtubule assembly (preventing polymerization of dimers) -> cell division is arrested during metaphase -> signal for apoptosis

20
Q

Tubulin-Binding Agents:

A

Tubulin-Binding Agents:

  • Vinca Alkyloids
    • Vincristine
    • Vinblastine
    • Vinorelbine
  • Taxnanes:
    • Paclitaxel
    • Docetaxel
21
Q

Vincristine

Class:

Toxicities:

A

Vincristine

Class: Tubulin-Binding Drug: Vinca-Alkaloid

Toxicities:

  • 1. Peripheral Neuropathy (~100%)
    1. Hyponatremia (SIADH)
    1. Some autonomic neuropathy -> reversible?
  • 4. Very little bone marrow suppression
  • 5. Autonomic dysfunction
22
Q

Myelosuppresion among vinca alkyloids

A

Vincristine: very little bone marrow suppression

Vinblastine/Vinorelbine: bone marrow suppression

23
Q

Paclitaxel, Docetaxel

Class:

Toxicities:

A

Taxanes

Class: Tubulin-Binding Agents - Taxanes

Toxicities:

  • Peripheral Neuropathy (especially hands and feet)
  • Muscle & Joint Pain
  • Hypersensitivity Reactions: 25-30%
  • Cardiac:
    • Bradycardia,
    • HB,
    • MI
  • Myelosuppresion
    • Neutropenia devels in almost all patients
    • 1% have a sepsis related death
    • 11% have sepsis related death if there is concurrent liver failure
24
Q

Signal Transduciton Modulating Agents:

A

Signal Transduciton Modulating Agents:

  • Anti-Hormone Drugs
    • Tamoxifen
    • Flutamine
  • Aromatase Inhibitors
  • Monoclonal Antibodies
    • Bevacizumab
25
Q

Signal Transduction Modulators

MOA:

A
  • Disrupt abberant growth factor: Receptor interactions in cancerous cells that prevents the intracellular signalling that would lead to cellular proliferation and survival

OR

  • Target mutated receptors that give a signal to proliferate without any growth factor bound
26
Q

Tamoxifen acts as

A
  • an estrogen ANT-agonist in certain cells: breast, ovarian
  • and an estrogen agonist in other cells (uterus, liver, bone)
27
Q

Flutamine acts as:

A

an androgen-antagonist, competitvely antagonizes testosterone and DHT

28
Q

Tamoxifen SE:

A

related to estrogen-AGONIST activity

  • DVT
  • Endometrial CA
  • Menopausal symptoms
  • increased bone density (good)
  • improves serum cholesterol panel (good)
29
Q

Flutamine SE:

A

r/t to androgen antagonist effects:

  • gynecomastia
  • hot flahses
  • muscle weakness
  • osteoporosis
  • methemoglobinemia
30
Q

MOA: Aromatase Inhibitors

A

Aromatase = enzyme complex that usually converts androgens into estrone in fatty tissues (breast)

MOA Aromatase Inhibitors:

Blocks actions of aromatase, blocks conversion of androgens into estrone -> decreases level of estrone in some post-menopausal women with breast cancer

31
Q

Bevacizumab

MOA:

A

Bevacizumab is a monoclonal antibody (signal transuduction modulator)

MOA: Blocks angiogensis by inhibiting vascular endothelial growth factor [VEGF].

Works for a limited amount of time and then cancer is able to adapt. :(

32
Q

Bevacizumab SE:

A

Hypertension with monoclonal antibodies = 35-45%

33
Q

Complete Response:

A

Complete dissapearance of all cancer without evidence of new disease for at least 1 month

34
Q

Partial Response

A

50% reduction in tumor size or other objective markers.

35
Q

Stable Disease:

A

A patient whose tumor size neither grows nor shrinks by more than 25%

36
Q

Progression

A

25% increase in tumor size or development of new lesions while on treatment.

37
Q

Most Common Drugs to cause problematic extravasation: (classes)

A

Anthracyclines

Vinca Alkaloids

Taxanes

38
Q

Alkylating Agents

MOA:

A

Alkylating Agents

MOA: Reactive alkyl groups form covalent bonds with nucleotide bases in DNA, RNA

“Cross-linkes guanine on the DNA helix, thereby making DNA stuck in coil. If it cannot uncoil, it cannot replicate.”

39
Q

To prevent methotrexate nephrotoxicity:

A

Alkalinize urine and hydrate!

Renal toxicit is usually permanent.

40
Q

In case of GI upset r/t methotrexate and 5FU

A

perforation is possible (more so for 5FU) and would be complicated by thrombocytopenia.

41
Q

Hydroxyl Free Radicals with Anthracyclines

A

Free radical production is greately stimulated by the interaction of doxorubicin with iron (blood)

42
Q

Anthracycline

Toxicities:

A

Anthracycline

Toxicities:

Doxorubicin/Daunorubicin

  1. Substanial Bone Marrow Suppression
    * Anemia, thrombocytopenia, low WBC 70% of patients
  2. Red/Orange Urine/Sweat
  3. Cardiotoxicity
  • May be more sensitive to cardiac depressive side effects of anestheticis even if normal resting echo.
  • Cumulative
43
Q

Cardiotoxicity of Anthracyclines

Acute vs Chronic

A

Caused by free radical production.

Acute: 10% -> Transient and Rare

  • Tachycardia
  • Arrthymias
  • ECG chagnes and acute ECF reduction
  • Usually lasts 1-2 months

Chronic: 2% with 60% fatality

  • Severe cardiomyopathy/CHF
  • Related to cumulative dose
  • Protective Therapies
    • Dexrazone: prevents free radical formation
    • ACE-Inhibitors
44
Q

Bleomycin in lymphoma patients

A

High risk for hypersensitivity.

Can cause fever, chills, confusion, hypotension, wheezing.

Test dose is reccomended for lymphona patients before standard doses.

Spring Pharm (11 decks)

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