Chemotherapeutic Drugs Flashcards
Form covalent alkyl bonds with nucleic acid bases resulting in _____ or _____ DNA cross-links which are toxic to cells undergoing ______
Intrastrand, interstrand, division.
The most important dose-limiting factor in the clinical use of alkylating drugs (esp busulfan)
Bone marrow suppression
Inhibition of plasma cholinesterase activity may be present up to ____ after administration of alkylating agents
2-3 weeks
Treats Hodgkin’s disease. SE: N/V, myelosuppression.
Herpes zoster is frequent
Mechlorethamine (nitrogen mustard)
Most frequently used chemo drug & is effective in tx of wide range of cancers & inflammatory dzs. Potent immunosuppressive properties
SE: pericarditis, pericardial effusion, myocarditis
Cyclophosphamide (nitrogen mustard)
Inappropriate secretion of arginine vasopressin hormone is seen in pts with doses of _____ mg/kg of ____
> 50; cyclophosphamide (nitrogen mustard)
Changes in renal or hepatic function have NOT been reported with which nitrogen mustard?
Melphalan
Produces remissions up to 90% of pts with chronic myelogenous leukemia but has no value in treating acute leukemia
Busulfan (alkyl sulfonate)
Mustard gas-related compounds used as an alkylating agent.
Wide spectrum of activity (intracranial tumors, melanomas, GI, hematologic malignancies)
High lipid solubility
Nitrosoureas
Clinical use of nitrosoureas is limited by profound drug induced _______ with exception of _____
Myelosuppression ;Streptozocin
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
Carmustine (nitrosoureas)
Carmustine can cause ____, _____, & ____ toxicity
Hepatotoxicity, nephrotoxicity, & CNS
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
Streptozocin (nitrosoureas)
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
Mitomycin (nitrosoureas)
Frequently designated as an alkylating but has NO alkyl group and cannot carry out alkylating reactions. Correctly classified as “alkylating-like”
Cisplatin (platinating drug)
IV only
High conc found in kidneys, liver, intestines, & testes, but poor _____ concentrations.
Cisplatin; CNS
______ is prominent and becomes the dose-limiting toxic effect of Cisplatin
Renal toxicity
______ & ______ may protect against the development of renal toxicity by dilution of the tubular urinary concentration of _______
Hydration & diuresis (mannitol & lasix); cisplatin
Allergic rxn: facial edema, bronchoconstriction, tachycardia, & hypotension may occurs minutes after injection of this drug
Cisplatin
What 3 analogues make up the nucleic acid synthesis inhibitors (antimetabolites)?
Folate analogues (methotrexate); Pyrimidine analogues (fluorouracil, premetrexed) Purine analogues (mercaptopurine, thioguanine)
Nucleic acid synthesis inhibitors (antimetabolites) are effective in destroying cells during ___ phase of the cell cycle in which DNA is synthesized
S
Used in malignant & nonmalignant disorders
Useful in tx of acute lymphoblastic leukemia in children but NOT in adults
Methotrexate
Most common side effects with methotrexate?
GI tract & bone marrow (leukopenia & thrombocytopenia)
What is the rescue technique for methotrexate?
Protecting normal cells from lethal damage by folate antagonists with sequential administration of folic acid
Correct alterations in DNA which occur during replication and transcription
Topoisomerase inhibitors
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)
Doxorubicin & Daunorubicin (anthracycline antibiotics)
CM from anthracycline antibiotics is a/w marked impairment of ___ function for as long as ___
LV; 3 years
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
First form of CM a/w topoisomerase inhibitors
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
2nd form of CM from topoisomerase inhibitors
_______ is an IV free radical scavenger and protects the heart from doxorubicin-associated damage
Dexrazoxane
Binds to DNA especially in rapidly proliferating cells.
Most important clinical use is tx of Wilms tumor in children & rhabdomyosarcoma
Dactinomycin (topoisomerase inhibitor)
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
Bleomycin
Why does Bleomycin cause pulmonary toxicity?
It concentrates in the lungs & is inactivated by a hydrolase enzyme which is relatively deficient in the lung tissues
Bleomycin causes necrosis of _____ and proliferation of _____ alveolar cells
Type 1; type 2
Cough, dyspnea, basilar rails
First signs of pulm toxicity from Bleomycin
Exertional dyspnea
Normal resting PaO2
Mild pulmonary toxicity from Bleomycin
Arterial hypoxemia at rest
Interstitial pneumonitis and fibrosis on X-ray
Lesions frequently in lower lobes and subpleural area
Severe pulm toxicity a/w Bleomycin
It is recommended inhaled O2 concentrations be maintained _______ in Bleomycin treated pts
Below 30%
What type of fluids may be better for Bleomycin & pulmonary toxicity pts? Why?
Colloids rather than crystalloids to decrease or prevent pulmonary interstitial edema
Intercalate DNA at specific sequences, creating free radicals, which cause strand breakage
Antitumor antibiotics
Hormonal treatment of cancer that disrupts growth factor receptor interactions
Single transduction modifiers
Single transduction modifiers:
Antiestrogens (tamoxifen)
Antiandrogens (flutamide, bicalutamide)
Monoclonal antibodies (trastuzumab, pertuzumab)
Aromatase inhibitors (anastrozole, letrozole)
What class control the structure of DNA and are responsible for uncoiling DNA?
Topoisomerase inhibitors
Which drug classes are related to secondary malignancies?
Alkylating agents & topoisomerase inhibitors
What are the commonly used nitrogen mustards?
Mechlorethamine, cyclophosphamide, melphalan, & chlorambucil
Which drug classes are alkylating drugs?
Nitrogen mustards, alkyl sulfonates, nitrosoureas, & triazenes
