Chemotherapeutic Drugs

Question 1

Form covalent alkyl bonds with nucleic acid bases resulting in _____ or _____ DNA cross-links which are toxic to cells undergoing ______

Answer 1

Intrastrand, interstrand, division.

Question 2

The most important dose-limiting factor in the clinical use of alkylating drugs (esp busulfan)

Answer 2

Bone marrow suppression

Question 3

Inhibition of plasma cholinesterase activity may be present up to ____ after administration of alkylating agents

Answer 3

2-3 weeks

Question 4

Treats Hodgkin’s disease. SE: N/V, myelosuppression.

Herpes zoster is frequent

Answer 4

Mechlorethamine (nitrogen mustard)

Question 5

Most frequently used chemo drug & is effective in tx of wide range of cancers & inflammatory dzs. Potent immunosuppressive properties
SE: pericarditis, pericardial effusion, myocarditis

Answer 5

Cyclophosphamide (nitrogen mustard)

Question 6

Inappropriate secretion of arginine vasopressin hormone is seen in pts with doses of _____ mg/kg of ____

Answer 6

> 50; cyclophosphamide (nitrogen mustard)

Question 7

Changes in renal or hepatic function have NOT been reported with which nitrogen mustard?

Answer 7

Melphalan

Question 8

Produces remissions up to 90% of pts with chronic myelogenous leukemia but has no value in treating acute leukemia

Answer 8

Busulfan (alkyl sulfonate)

Question 9

Mustard gas-related compounds used as an alkylating agent.
Wide spectrum of activity (intracranial tumors, melanomas, GI, hematologic malignancies)
High lipid solubility

Answer 9

Nitrosoureas

Question 10

Clinical use of nitrosoureas is limited by profound drug induced _______ with exception of _____

Answer 10

Myelosuppression ;Streptozocin

Question 11

Widest clinical use. Bc of its ability to rapidly cross BBB it is used to treat meningeal leukemia & primary as well as metastatic brain tumors

Answer 11

Carmustine (nitrosoureas)

Question 12

Carmustine can cause ____, _____, & ____ toxicity

Answer 12

Hepatotoxicity, nephrotoxicity, & CNS

Question 13

Has a unique affinity for Beta cells of the islets of Langerhans & has proved useful in the tx of pancreatic islet cell carcinoma & malignant carcinoid

Answer 13

Streptozocin (nitrosoureas)

Question 14

IV route widely distributed in tissues but does NOT readily enter the CNS (not good choice for brain tumors).
Induces pulmonary fibrosis with thoracic radiation & oxygen therapy

Answer 14

Mitomycin (nitrosoureas)

Question 15

Frequently designated as an alkylating but has NO alkyl group and cannot carry out alkylating reactions. Correctly classified as “alkylating-like”

Answer 15

Cisplatin (platinating drug)

Question 16

IV only

High conc found in kidneys, liver, intestines, & testes, but poor _____ concentrations.

Answer 16

Cisplatin; CNS

Question 17

______ is prominent and becomes the dose-limiting toxic effect of Cisplatin

Answer 17

Renal toxicity

Question 18

______ & ______ may protect against the development of renal toxicity by dilution of the tubular urinary concentration of _______

Answer 18

Hydration & diuresis (mannitol & lasix); cisplatin

Question 19

Allergic rxn: facial edema, bronchoconstriction, tachycardia, & hypotension may occurs minutes after injection of this drug

Answer 19

Cisplatin

Question 20

What 3 analogues make up the nucleic acid synthesis inhibitors (antimetabolites)?

Answer 20

Folate analogues (methotrexate);
Pyrimidine analogues (fluorouracil, premetrexed)
Purine analogues (mercaptopurine, thioguanine)

Question 21

Nucleic acid synthesis inhibitors (antimetabolites) are effective in destroying cells during ___ phase of the cell cycle in which DNA is synthesized

Answer 21

S

Question 22

Used in malignant & nonmalignant disorders

Useful in tx of acute lymphoblastic leukemia in children but NOT in adults

Answer 22

Methotrexate

Question 23

Most common side effects with methotrexate?

Answer 23

GI tract & bone marrow (leukopenia & thrombocytopenia)

Question 24

What is the rescue technique for methotrexate?

Answer 24

Protecting normal cells from lethal damage by folate antagonists with sequential administration of folic acid

Question 25

Correct alterations in DNA which occur during replication and transcription

Answer 25

Topoisomerase inhibitors

Question 26

Acts by binding to DNA resulting in changes in the DNA helix and interfere with the ability of nucleic acids to serve as a template during replication (drug not class)

Answer 26

Doxorubicin & Daunorubicin (anthracycline antibiotics)

Question 27

CM from anthracycline antibiotics is a/w marked impairment of ___ function for as long as ___

Answer 27

LV; 3 years

Question 28

Characterized by relatively benign changes on the ECG (nonspecific ST-T changes, decreased QRS voltage, PVC’s, SVT, cardiac conduction abnormalities, left axis deviation)
Resolve 1-2 months after therapy
Acute reversible decrease in EF w/in 24 hrs after single dose

Answer 28

First form of CM a/w topoisomerase inhibitors

Question 29

Characterized by insidious onset of symptoms such as dry nonproductive cough, suggesting bronchitis, follow by rapidly progressive heart failure that is unresponsive to inotropic drugs & mechanical ventricular assistance

Answer 29

2nd form of CM from topoisomerase inhibitors

Question 30

_______ is an IV free radical scavenger and protects the heart from doxorubicin-associated damage

Answer 30

Dexrazoxane

Question 31

Binds to DNA especially in rapidly proliferating cells.

Most important clinical use is tx of Wilms tumor in children & rhabdomyosarcoma

Answer 31

Dactinomycin (topoisomerase inhibitor)

Question 32

Possesses a tripeptide component that binds DNA & a metal-binding region. In the presence of oxygen and either iron or copper, it produces free radicals which create DNA breaks.

Tx: testicular carcinoma & palliative tx of squamous cell carcinomas of the head, neck, esophagus, skin, & GU

Answer 32

Bleomycin

Question 33

Why does Bleomycin cause pulmonary toxicity?

Answer 33

It concentrates in the lungs & is inactivated by a hydrolase enzyme which is relatively deficient in the lung tissues

Question 34

Bleomycin causes necrosis of _____ and proliferation of _____ alveolar cells

Answer 34

Type 1; type 2

Question 35

Cough, dyspnea, basilar rails

Answer 35

First signs of pulm toxicity from Bleomycin

Question 36

Exertional dyspnea

Normal resting PaO2

Answer 36

Mild pulmonary toxicity from Bleomycin

Question 37

Arterial hypoxemia at rest
Interstitial pneumonitis and fibrosis on X-ray
Lesions frequently in lower lobes and subpleural area

Answer 37

Severe pulm toxicity a/w Bleomycin

Question 38

It is recommended inhaled O2 concentrations be maintained _______ in Bleomycin treated pts

Answer 38

Below 30%

Question 39

What type of fluids may be better for Bleomycin & pulmonary toxicity pts? Why?

Answer 39

Colloids rather than crystalloids to decrease or prevent pulmonary interstitial edema

Question 40

Intercalate DNA at specific sequences, creating free radicals, which cause strand breakage

Answer 40

Antitumor antibiotics

Question 41

Hormonal treatment of cancer that disrupts growth factor receptor interactions

Answer 41

Single transduction modifiers

Question 42

Single transduction modifiers:

Answer 42

Antiestrogens (tamoxifen)
Antiandrogens (flutamide, bicalutamide)
Monoclonal antibodies (trastuzumab, pertuzumab)
Aromatase inhibitors (anastrozole, letrozole)

Question 43

What class control the structure of DNA and are responsible for uncoiling DNA?

Answer 43

Topoisomerase inhibitors

Question 44

Which drug classes are related to secondary malignancies?

Answer 44

Alkylating agents & topoisomerase inhibitors

Question 45

What are the commonly used nitrogen mustards?

Answer 45

Mechlorethamine, cyclophosphamide, melphalan, & chlorambucil

Question 46

Which drug classes are alkylating drugs?

Answer 46

Nitrogen mustards, alkyl sulfonates, nitrosoureas, & triazenes