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PAS - PHARM > Anticancer Drugs > Flashcards

Anticancer Drugs Flashcards

1
Q

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
A

specific
DNA
bifunctional

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2
Q

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

A 
PERIAPICAL 
Clindamycin
Amoxicillin
Clauvulanic acid
PERIODONTAL
SIALADENTITIS
BLEEDING
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3
Q

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
A

Methocarboamol (Robaxin), Cyclobenzaprine (Flexeril), Carisoprodal (Soma), Metaxalone (Skelaxin), Tizanidine (Zanaflex), Baclofen, Oxazepam

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4
Q

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
A 
RITUXIMAB
immunoglobulins
Humanised
Fab
Fb
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5
Q

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
A 
ASPARAGINASE
tumor
asparignase
ALL
hypersensitivty 
hepatitis, 
pancreatitis ***
PEG-L
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6
Q

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
A 
LEUPROLIDE, GOSERELIN
GnRH
agonists
negative 
pituitary
gonadotropin
tumor
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7
Q

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
A

TRETINOIN
ISOTRETINOIC ACID
ARSENIC TRIOXIDE

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8
Q

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

A 
PACLITAXEL
M
polymerization
microtubules
ovary, breasts
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9
Q

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 –
-_______
-_______
-________

A 
nikolsky
keratinocytes
cyclosporine
corticosteroids
infliximab
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10
Q
  • 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
A

ZINC SULFATE
wound
epithelial
inflammation

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11
Q

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
A

hepatitis B
neurologic
neurotoxicity
parasthesias

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12
Q
  • 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
A 
AMIFOSTINE
VITAMIN E
GLUTAMINE
PROPANTHELINE
antimuscarinic drug **
XHYLOCAINE, LIDOCAINE
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13
Q

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, ________ )

A

ANASTRAZOLE
aromatase
bisphosphonates

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14
Q

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

A 
FILGRASTIM
SARGRAMOSTIM
granulocytes
marrow
macrophages
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15
Q

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

A 
FLUTAMIDE
nonsteroidal
testosterone
prostate
prostrate
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16
Q

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 –
______, ________

A

high plasma protein binding
salicylates, Sulfonamides, phenytoin
pneumonitis
nephrotoxicity *

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17
Q

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

A

thymidilate synthetase

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18
Q

BLOOD LEUKEMIAS - COMBINATION THERAPIES

  • ALL – _______, _______, _______
  • AML – __________, _______
  • CML – _________( tyrosine kinase inhibitor - produced by ________)
  • CLL – ______, _____ (CD20 expression)
A 
– Daunorubicin, Vincristine, Prednisone
Cytosine arabinoside, Daunorubicin
Imatinib
philedelphia chromosome
Fludarabine, Rituximab
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19
Q

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 ______
A

blood vessels
mouth
feeling

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20
Q

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)

A 
ETOPOSIDE
topoisomerase II
lung, testicular
myelosuppression
alcohol
21
Q

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)

A 
thalidomide, lenalidomide
antiangiogenesis
TNF
T
myelodysplastic syndrome
22
Q

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)

A 
thrombocytopenia
hair
spermatogenesis
cardiotoxicity
nitrous
23
Q

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

A

hydroxyurea
diphosphate reductase
CML
myeloproliferative

24
Q

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)

A 
scission
DNA
RNA
protein
G2, M
interstitial pneumonitis
fibrosis
toxicity
25
Q

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,
A

tumor
host
specific
dividing

26
Q

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

A 
BBB
AML
stem
white blood
weeks, months
27
Q

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
  • ________, _________
A 
CISPLATIN
interstrand
intrastrand
breaks
specific
radiosensitizer
nephrotoxicity
AMIFOSTINE
CARBOPLATIN, OXALIPLATIN
28
Q

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

A 
Nitrogen mustards
alkyl sulfonates
ethylenimines
triazenes
nitrosoureas
myelosuppression
gastrointestinal
29
Q

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 \_\_\_\_\_\_\_\_
A

pediatric
RNA polymerase
topoisomerase II

30
Q

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)

A 
Vinblastine, Vincristine
microtubular proteins
ALL
neurotoxicity
ALL
philedelphia chromsome
31
Q

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)

A 
DNA
non phase 
Danurubicin 
AML, ALL
Topoisomerase II
cardiac toxicity 
liposomal 
plasma
32
Q

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)
A 
procarbizine
haematological
pulmonary
MAO
disulfram
33
Q

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 ____

A 
hydrophilic
FOLINIC
dihydrofolate reductase
dUMP, dTMP
tetrahydrafolate
dump, dtmp
34
Q

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

A

trastuzumab

HER2

35
Q

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

A 
ALL, CLL
hypercalcemia
spinal cord
antiemetic
pain 
insomnia
Cushingoid
36
Q

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
A 
folic acid
purine
pyrimidine
fraudulent
S phase
Methotrexate
Cytarabine
Fluorouracil
37
Q

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)
A

anti-depressants

anti-anxiety

38
Q

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
A

proliferation
dedifferentation
proto oncogenes
tumor suppressor

39
Q

___________
-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)

A

bisphosphonates
osteoclast
apoptosis
ARONJ

40
Q

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

A

opioids
diet
ORAL HYGIENE

41
Q

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
A

mitoxantrione

42
Q

-___________ (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

A 
MAGIC MOUTHWASH
CRYOTHERAPY
Oxaliplatin
FLIGRASTIM
PALIFERMIN
43
Q

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

A 
Cyclophosphamide
lymphocytes
hemorrhagic cystitis
MESNA
Thiotepa
44
Q

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)

A 
ESTROGENS
SERM
adenocarcinoma
initial flare
hot flashes
SSRIs
TOREMIFENE
MEGESTROL
progesterone
45
Q

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)

A 
2-3
PILOCARPINE, CVIMELINE
taste buds
Zinc sulfate
MALNUTRITION
46
Q

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

A

telomerase
angiogenesis
immortality

47
Q

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

A 
IMATINIB
protein tyrosine kinase
philedelphia chromosome
skin
melanosis
melanogenesis
48
Q

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
A

first order kinetics

interval

49
Q

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)
A 
oral mucositis
speech, eating, swallowing
DNA
4-7
2-4
methotrexate, etoposide

PAS - PHARM (26 decks)

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