Anticancer Drugs Flashcards
Alkylating Agents
- 6 CLASSES (Form ‘alkyl radicals’ that form covalent linkages with nucleophilic moieties)
- Not cell cycle _____ but principle effect is during ____ synthesis
- Most are ______ (two alkylating groups) – cross link two _______ sites
- Cause intra and inter chain cross-linking
- Interfere with transcription and replication
specific
DNA
bifunctional
OTHER ORAL COMPLICATIONS
_______ INFECTIONS –
-Damaged lining in the mouth and weakened immune system
-Risk is raised by xerostomia during radiation therapy
-Managed with antibiotics (_______ or ______ with _______ antifungal and antiviral drugs
Rarely, the progression of the infection may cause cavernous sinus thrombosis and Ludwig angina –
–Immediate transfer to the nearest hospital and aggressive therapy with antibiotics are crucial and may save patients life
-_______ DISEASE
-_________
-_________ – Due to decreased platelet count, small red spots on lips, soft palate or bottom of the mouth) or severe at the gum line and from ulcers in the mouth
PERIAPICAL Clindamycin Amoxicillin Clauvulanic acid PERIODONTAL SIALADENTITIS BLEEDING
DRUG TREATMENT FOR MOUTH AND JAW STIFFNESS
- ASA
- IBUPROFEN
- BENZODIAZAPENES such as diazepam
- muscle relaxants: Methocarboamol (Robaxin), Cyclobenzaprine (Flexeril), Carisoprodal (Soma), Metaxalone (Skelaxin), Tizanidine (Zanaflex), Baclofen, Oxazepam
Methocarboamol (Robaxin), Cyclobenzaprine (Flexeril), Carisoprodal (Soma), Metaxalone (Skelaxin), Tizanidine (Zanaflex), Baclofen, Oxazepam
MONOCLONAL ANTIBODIES - _______
- ________ produced by cell culture selected to react with antigen specifically expressed on cancer cells
- _______– Hybrids of human antibodies
- They attach to specific antigen with __ portion of the molecule and __ is left jutting out – this activates host’s immune mechanisms and cancer cell is killed by complement mediated lysis
- Monoclonal abs can attach to and inactivate growth factor receptors on cancer cells
RITUXIMAB immunoglobulins Humanised Fab Fb
ENZYMES
\_\_\_\_\_\_\_\_ – -Isolated from bacteria -Inhibit protein synthesis in tumor cells by depriving them of amino acid \_\_\_\_\_\_\_ -G phase specific Use – \_\_\_\_ SE – \_\_\_\_\_\_\_ reactions,\_\_\_\_\_\_, \_\_\_\_\_\_\_ increased bleeding risk \_\_\_\_\_ ASPARAGINASE – To decrease immunogenicity
ASPARAGINASE tumor asparignase ALL hypersensitivty hepatitis, pancreatitis *** PEG-L
DRUGS AFFECTING SEX HORMONES
______,_______
- Synthetic analogues of _____
- agonistsduring short term /pulsatile therapy
- Long term administration – _____ feedback loop with _____ gland (Inhibit ______ secretion, ovarian and testicular steroidogenesis)
- SE – Initial tumor flare (pain at tumor site and hypercalcemia)
- Hot flashes, erectile dysfunction, gynecomastia, hypercholesterolemia, hyperglycemia
LEUPROLIDE, GOSERELIN GnRH agonists negative pituitary gonadotropin tumor
DIFFERENTIATION AGENTS
RETINOIDS -Can inhibit cell growth, induce differentiation and apoptosis \_\_\_\_\_\_\_ Use – Acute promyelocytic leukemia \_\_\_\_\_\_\_\_\_\_ Childhood neuroblastoma \_\_\_\_\_\_\_\_\_ has revolutionized the treatment of APL (acute promyelocytic leukemia) SE – QTc prolongation
TRETINOIN
ISOTRETINOIC ACID
ARSENIC TRIOXIDE
TAXANES
___________
-Bark of yew tree
-MOA – cell replication in __ phase by promoting ________ and stabilization of ______ (inhibiting depolymerization)
-Formulated in Cremophor E1 and alcohol – infusion reactions
-Premedicated with steroids and antihistaminics
-Albumin bound drug (novel formulation)
-Use – Metastatic cancers of ____ and _____, NSCLC, Pancreatic adenocarcinoma with Gemcitabine
PACLITAXEL M polymerization microtubules ovary, breasts
STEVEN JOHNSON SYNDROME
-Toxic epidermal necrolysis TEN – (different forms but same entity)
-Rare, life-threatening conditions involving both the cutaneous and mucosal membranes.
-Exfoliation implies a positive _______ sign (epidermal detachment caused by slight rubbing of the skin) –
–Destruction of ________ by apoptosis.
Management –
-_______
-_______
-________
nikolsky keratinocytes cyclosporine corticosteroids infliximab
- LASER THERAPY (wavelength about 650 nm, power setting 40 mW and a dose of 2 J/cm2at each square centimeter of tissue)
- _________ favors ______ healing –
- Preservation of _____ tissue integrity,
- Increases re-epithelialization
- Acts against ________and bacterial development
ZINC SULFATE
wound
epithelial
inflammation
SIDE EFFECTS CONTD
- Reactivation of _______
- ______ complications (seizures, peripheral and cranial neuropathy, myelopathy, aseptic meningitis, cerebellar syndrome, stroke, encephalitis)
- -________ (hyper-excitability, ataxia of the extremities)
- -______ in the mouth and throat
- Hypothyroidism
- Anemia is not common
hepatitis B
neurologic
neurotoxicity
parasthesias
- IV immunoglobulins and histamine gels for prevention
- _______ (cytoprotective drug suppresses ROS)
- VITAMIN E (antioxidant against ROS)
- GLUTAMINE
- ________ causes hypo-salivation, thus reducing mucosal exposure to agents in saliva, _______ drug
- XYLOCAINE AND LIDOCAINE solutions
AMIFOSTINE VITAMIN E GLUTAMINE PROPANTHELINE antimuscarinic drug ** XHYLOCAINE, LIDOCAINE
DRUGS AFFECTING SEX HORMONES
_________–
Nonsteroidal reversible inhibitor of _______ enzyme
Use – Postmenopausal hormone receptor positive breast cancer
SE – Arthralgia, myalgia, hot flashes, osteoporosis (add calcium and vitamin D supplementation, ________ )
ANASTRAZOLE
aromatase
bisphosphonates
CLINICAL USES OF CYTOKINES
Aldesleukin (IL2) – Increase lymphocyte differentiation and increase NK Cells, used in renal cell carcinoma and metastatic melanoma
Interleukin 11 – Increase platelet formation, used in thrombocytopenia
_______ (G-CSF) – Increase ______, used for _____ recovery
__________ (GM-CSF) – Increase granulocytes and ______, used for marrow recovery
Erythropoietin – To treat anemias, especially associated with renal failure
Thrombopoietin – Thrombocytopenia
FILGRASTIM SARGRAMOSTIM granulocytes marrow macrophages
DRUGS AFFECTING SEX HORMONES
__________
_______ antiandrogen that directly competes with _______ binding site in ______ cells
Use – Combination with GnRH agonist to prevent the flare and in castration resistant _____ cancer
SE – Hot flashes, decreased libido, gynecomastia
FLUTAMIDE nonsteroidal testosterone prostate prostrate
Antimetabolites -METHOTREXATE
Drug interactions –
-____________ binding (displaced by ________,_________, _________)
-Salicylates, Probenecid and Penicillins compete for tubular secretion
-NSAIDS reduce renal blood flow and increase nephrotoxicity
-PPIs delay clearance
Side effects –
______, ________
high plasma protein binding
salicylates, Sulfonamides, phenytoin
pneumonitis
nephrotoxicity *
Fluorouracil
- IV bolus or continuous infusion (half life of 10 -20 mins) over 96 hours
- Topical – Actinic keratosis and noninvasive skin cancers
- Intra-arterial – Metastasis to liver and head and neck _cancers
MOA: inhibits _________ which converts dUMP to dTMP
thymidilate synthetase
BLOOD LEUKEMIAS - COMBINATION THERAPIES
- ALL – _______, _______, _______
- AML – __________, _______
- CML – _________( tyrosine kinase inhibitor - produced by ________)
- CLL – ______, _____ (CD20 expression)
– Daunorubicin, Vincristine, Prednisone Cytosine arabinoside, Daunorubicin Imatinib philedelphia chromosome Fludarabine, Rituximab
TISSUE AND BONE LOSS
- Destruction of very small _______within the bone resulting in bone death/fractures/infection
- Destruction of tissue inside the ______can result in loss of ______
blood vessels
mouth
feeling
PODOPHYLLOTOXINS
_________
-Mandrake plant
-MOA – Induce DNA strand breaks by inhibiting ________
-Use – First line treatment for small cell lung cancer and refractory testicular cancer
-SE – _______, hypotension and ______ intoxication (dissolved in ethanol)
ETOPOSIDE topoisomerase II lung, testicular myelosuppression alcohol
MISC AGENTS
_________, __________
-MOA – Complex and misunderstood, _________ and immune system modulation, inhibits TNF production, stimulates T cell proliferation, IL-2 and interferon release
-Uses – _________ (pre-leukemic syndrome), Multiple myeloma with Dexamethasone, HIV related aphthous ulcers, Rheumatoid arthritis, CGVHD
-SE – Sedation, rash, neuropathy, constipation and venous thrombosis (anticoaglulation therapy)
thalidomide, lenalidomide antiangiogenesis TNF T myelodysplastic syndrome
GENERAL SIDE EFFECTS OF CYTOKINES
-_________ after 10-14 days
-_____ loss
-Nausea, vomiting, diarrhea and fatigue (most frequent)
-Defects in ________
-Hand-foot syndrome
-_________(left ventricular impairment or CHF leading to hypertension), thromboembolism, pericardial thickening or arrhythmias
-Bleomycin induced pulmonary fibrosis (_______ is contraindicated)
Hepatic toxicity (Jaundice)
thrombocytopenia hair spermatogenesis cardiotoxicity nitrous
MISC AGENTS
_______
-MOA – Inhibits DNA synthesis by blocking action of ribonucleoside _________
-Uses – ___, ______ disorders, to reduce rapidly increasing blast cells in acute leukemias, Polycythemia vera
-In sickle cell anemia to reduce pain crisis and reduce the need for blood transfusions
-SE – myelosuppression and megaloblasgtic anemia
hydroxyurea
diphosphate reductase
CML
myeloproliferative
Bleomycin
MOA – DNA _____ and fragmentation with inhibition of ____ repair, inhibit ____and _____ synthesis
Cell cycle specific – __ and __ phase
Use – head and neck cancers, testicular cancers and Hodgkin’s lymphoma
Malignant pleural infusion – Direct instillation into pleural space
Minimal nausea and vomiting, no myelosuppression, or local tissue toxicity
Combination protocols
SE – Major dose limiting __________ progressing to pulmonary _____ and pulmonary insufficiency
Caution – Exacerbation/precipitation of pulmonary ____ caused by supplemental oxygen administration (general anesthesia)
scission DNA RNA protein G2, M interstitial pneumonitis fibrosis toxicity
Principles of Chemotherapy
GOAL – Eradicate every viable ___ cell without significantly damaging the ___ cell
CLASSIC CHEMOTHERAPY AGENT –
- Not tumor cell _____
- Kills all actively _____ cell
- Unintended destruction of gastrointestinal, bone marrow, hair follicles,
tumor
host
specific
dividing
CYTARABINE (Cytosine Arabinoside) –
Crosses ____ (40-50% conc than in plasma)
Most active single drug for ____ in adults – 25% complete remission, given as combination therapy
AraC + Daunorubicin
AML –
___ cells,
_____ cells
Progresses rapidly and is typicall fatal within ____ or _____ if left untreated
BBB AML stem white blood weeks, months
PLATINUM AGENTS
_______
- An atom of platinum surrounded by 2 chlorides
- Produces ______ and _______ cross-links in DNA causing ____
- Not cell cycle _____
- _______ when used concurrently with radiotherapy
- Uses – Carcinoma testis, ovary, transitional bladder cancer, small and non small cell lung cancer and head and neck cancers
- SE – ________ is dose limiting, ototoxic
- Concurrent AMIFOSTINE and saline hydration is given to reduce renal toxicity
- ________, _________
CISPLATIN interstrand intrastrand breaks specific radiosensitizer nephrotoxicity AMIFOSTINE CARBOPLATIN, OXALIPLATIN
Alkylating Agents
- _______ – Chlorambucil, Cyclophosphamide, Estramustine, Ifosfamide, Mechlorethamine, Melphalan
- ________ – Busulfan
- ________ – Thiotepa
- _____ – Dacarbazine
- _______ – Carmustine, Lomustine, Streptozocin
SE –
All cause _________
and _______ disturbance
Long term use – ______ (suppression of gametogenesis), increased risk of acute non-lymphocytic leukemia, other malignancies
Nitrogen mustards alkyl sulfonates ethylenimines triazenes nitrosoureas myelosuppression gastrointestinal
Dactinomycin
\_\_\_\_\_ tumor (Wilms, Ewing, Embryonal rhabdomyosarcoma) -Intercalates in the minor groove between adjacent guanine-cytosine pairs, interfering with movement of --\_\_\_\_\_\_\_ along the gene – preventing transcription Also act on \_\_\_\_\_\_\_\_
pediatric
RNA polymerase
topoisomerase II
VINCA ALKALOIDS
______, ________
-Arrest cell division in metaphase by binding to _______ proteins that form mitotic spindle
-Use – ___, Hodgkin’s
-SE – _______ (peripheral and autonomic), constipation, ileus, paresthesias, neutropenia
-Caution – Never intrathecal (Ascending fatal paralysis)
-Liposomal formulation –
Relapsed ___ (pts who do not have philedelphia chromsome mutation)
–Increases duration and decrease toxicity (neurotoxicity)
Vinblastine, Vincristine microtubular proteins ALL neurotoxicity ALL philedelphia chromsome
ANTITUMOR ANTIBIOTICS
-Produced by streptomycetes species
-Intercalate with ___ to form irreversible complexes that inhibit cell division
-______ specific
ANTHRACYCLINES –
-_____ (___,____), doxorubicin (Broad range)
-_________ inhibitors (double stranded DNA breaks during DNA replication)
-SE – ______
-liposomal encapsulated forms – Provide increased _____ circulation time and decreased cardiomyopathy, different indications (Karposi sarcoma related to AIDS etc)
DNA non phase Danurubicin AML, ALL Topoisomerase II cardiac toxicity liposomal plasma
MISC AGENTS
__________
- MOA – Prevents __ and ____ synthesis
- Use – CNS malignancies and Hodgkin’s
- For Multiple myeloma in combination with alkylating agents and Vinca alkaloids
- SE – ________ toxicity (leukopenia, thrombocytopenia), _____ toxicity
- Is a ____ inhibitor, warn against tyramine rich foods and antidepressants
- has ______ like reaction (avoid alcohol)
procarbizine haematological pulmonary MAO disulfram
Methotrexate
-Very ______, third space fluid accumulation (ascitic, pleural, peritoneal), drug reservoir – increased toxicity
________ acid rescue – bypasses the blockage of ____________ in normal cells (reduced severity of mucositis and myelosuppression)
MOA:
For the conversion of ____ to _____, there is a cofactor required. The cofactor is ________ which is formed from dihydrofolate
methotrexate inhibits function of that cofactory and ____ is not converted to ____
hydrophilic FOLINIC dihydrofolate reductase dUMP, dTMP tetrahydrafolate dump, dtmp
BIOLOGIC RESPONSE MODIFIERS
-Interferons, Interleukins, Hematopoietic growth factors, Monoclonal antibodies
Example –
_________ –
-A monoclonal antibody specifically used for breast cancer that is ____ receptor positive
-Used alone or with other chemotherapy medications
trastuzumab
HER2
HORMONE AGONISTS AND ANTAGONISTS
GLUCOCORTICOIDS
-Combination therapy(___, ____, Lymphomas, Multiple Myeloma)
Supportive care –
–Reduce ________
(bone metastasis)
–_______ compression
–______
–____management
Dexamethasone, Prednisone, Methylprednisone
SE – _____, gastritis, elevated blood glucose
Prolonged use – ______ appearance, hypertension, osteoporosis, immune suppression
ALL, CLL hypercalcemia spinal cord antiemetic pain insomnia Cushingoid
Antimetabolites
- Marked structural resemblance to ______, _____ and ________bases
- _______ substrates for biochemical reactions
- Effect on __ Phase (DNA synthesis phase)
- Interferes with growth of rapidly proliferating cells (oral mucosa toxicity)
- Folic acid analogues – ________ (Folate antagonist)
- Purine analogues – Mercaptopurine, Thioguanine, Fludarabine
- Pyrimidine analogues – __________, ________ Floxuridine, Gemcitabine
folic acid purine pyrimidine fraudulent S phase Methotrexate Cytarabine Fluorouracil
mouth and jaw stiffness
MANAGE:
- Medical devices (bite openers made from acrylic resin, metal)
- Pain treatment
- Muscle relaxants
- Jaw exercises
- __________(Tri-cyclics like Amitriptyline, SSRIs)
- ________ drugs (BENZODIAZEPINES)
anti-depressants
anti-anxiety
Hallmark of Cancer Cells
CANCER CELLS VERSUS NORMAL CELLS – -Uncontrolled \_\_\_\_\_\_ -\_\_\_\_\_\_\_\_ and loss of function -Invasiveness -Metastasis GENESIS OF CANCER CELLS – -Genetic change --Activation of \_\_\_\_\_\_\_\_ to oncogenes --Inactivation of \_\_\_\_\_\_\_\_\_genes -Hormonal action -Co-carcinogens -Tumor promoter effects
proliferation
dedifferentation
proto oncogenes
tumor suppressor
___________
-Zoledronic acid, Pamidronate
MOA – inhibit ______ activity, and promote _____
-Bone pain associated with metastasis arising from breast, prostate, lung carcinoma and multiple myeloma
-SE – Fever, flu like syndrome, decreased renal function, hypocalcemia and ______ (anti-resorptive agent induced osteonecrosis of jaw)
bisphosphonates
osteoclast
apoptosis
ARONJ
SEVERE PAIN –______ and changes in _____
-Pain medications, muscle relaxants, anti anxiety drugs and antidepressants
________ – Protocols recommend dental intervention before chemotherapy
-Dental floss and oral rinses (Sterile water or physiologic saline solution are more effective than chlorhexidine)
-Povidone iodine rinses
opioids
diet
ORAL HYGIENE
ANTHRACENEDIONE-anti tumor
_________
- anthraquinone antibiotic (antibiotic, antiviral, antiprotozoal and immunomodulating)
- MOA – ___ strand breaks
- free radicalgeneration is low (low risk of cardiotoxicity)
- SE – Bluish green discoloration of urine and sclera
- Effective against resistant cancers
mitoxantrione
-___________ (Diphenhydramine, viscous lidocaine, bismuth subsalicylate, and corticosteroids)
-_________ 5-30 mins before chemotherapy (local vasoconstriction, reducing mucosal blood flow and thus the exposure)
-Cryotherapy is contraindicated in patients treated with _______, to eliminate neurological side effects such as mandibular stiffness.
Granulocyte-colony stimulating factor (G-CSF) – ________
________ IV – Mucocutaneous epithelial human growth factor
MAGIC MOUTHWASH CRYOTHERAPY Oxaliplatin FLIGRASTIM PALIFERMIN
Alklyating Agents
___________ –
Broad spectrum (induction, maintenance, remission)
Pronounced effect on _______ –
–Conditioning for bone marrow transplant
–Immunosuppressive (autoimmune disorders)
-Two active metabolites – Phosphoramide mustard and Acrolein (Toxic to bladder – _________ and dysuria)
-_____ (sodium 2 mercaptoethane sulfonate) or N-acetylcysteine, chemoprotectants
______ –
-Directly instilled into bladder for superficial cancer
Cyclophosphamide lymphocytes hemorrhagic cystitis MESNA Thiotepa
DRUGS AFFECTING SEX HORMONE STATUS
SEX HORMONES – ________ – Advanced prostatic cancer and postmenopausal breast cancer
-TAMOXIFEN – ____
USES – ________ of breast with positive Estrogen or Progesterone receptor status
–Endometrial and ovarian cancers
-SE – intial flare, bone pain, hypercalcemia
–hot flashes, thromboembolism
Metabolized by cytochrome P450, _____inhibit hepatic metabolism
TOREMIFENE
_______ (________ for endometrial, breast and renal cell carcinoma)
ESTROGENS SERM adenocarcinoma initial flare hot flashes SSRIs TOREMIFENE MEGESTROL progesterone
XEROSTOMIA –
-Dryness begins after 1 week and it takes around ___ months to recover (complete recovery may not be seen sometimes)
-Saliva substitutes and medications that help make more saliva (_______ and _______)
DYSGUESIA –
Damage to ______
Most patients – Returns to normal in 6 to 8 wks, sometimes permanent with radiation therapy
_______ supplements
________ AND FATIGUE –
Liquid diet and feeding tube within 3 to 4 weeks
Team – Speech and swallowing therapists, dietician, psychologist (risk of aspiration and pneumonia, constipation with opioids) +
DENTAL SPECIALIST (Replace missing teeth and damaged area with artificial devices to help swallowing)
2-3 PILOCARPINE, CVIMELINE taste buds Zinc sulfate MALNUTRITION
telomerase and angiogenesis
Nutrition – 1-2 mm size by diffusion, blood supply through ________ (a response to growth factors - VEGF, PDGF, FGF, and TGF)
________ Expression – Confers _______ on a cancer cell
telomerase
angiogenesis
immortality
MONOCLONAL ANTIBODIES
______
-A ___________ inhibitor
-Use – Adults and children who have been newly diagnosed with ________ positive chronic myeloid leukemia (Ph+ CML) in chronic phase
-Dermatofibrosarcoma protuberans (DFSP), tissue under the ___ grows out of control
-SE – ______ – Bluish-brown pigmentation on the hard palate, gingiva, teeth, and perioral region
-Occurs with Imatinib therapy – effects c-kit, a tyrosine kinase receptor with regulatory action on ________ –
–Overstimulation
Dose related and reversible
IMATINIB protein tyrosine kinase philedelphia chromosome skin melanosis melanogenesis
Useful Application of Cancer Chemotherapy
- Susceptible tumor cells
- Resistant host cells
- Intolerable local or systemic toxicity
- Adequate concentration
- Sufficient period
- Cell burden (blood supply and debulking)
- ___________
- _______between cycles
- Combination
- Resistance
first order kinetics
interval
ORAL SIDE EFFECTS
- ________
- Most common painful inflammatory reaction of the oral mucosa
- Infiltration of the inflammatory cells followed by epithelial disruption and ulceration (erythema, burning, odema and ulcers – impacting ____, ____ and ______)
- Injured tissue releases reactive oxygen species (ROS) which damage ____
- Arises ___ days after the initiation of a high dose course and disappears ___ weeks after the treatment is completed
- _______ and ______ are secreted in saliva (favors oral toxicity)
oral mucositis speech, eating, swallowing DNA 4-7 2-4 methotrexate, etoposide
