Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Pharmacology > Anticancer Drugs > Flashcards

Anticancer Drugs Flashcards

1
Q

General MOA of antimetabolites

A

Target pathways related to nucleotide and nucleic acid synthesis

Cell-cycle specific –> S-phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Methotrexate MOA

A

Antimetabolite -

Folate analog that competitively inhibits dihydrofolate reductase –> decreased synthesis of dTMP and purine nucleotides –> decreased DNA synthesis –> cell death

Undergoes conversion to a series of polyglutamates. Process is catalysed by folypolyglutamate synthase (FPGS). They increase the inhibitory potency of MTX for additional sites, including, thymidylate synthase and enzymes of de novo purine biosynthetic pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Methotrexate PK

A

After high doses, MTX undergoes hydroxylation at the 7 position –> hydroxylated derivative is less hydrosoluble and may lead to crystalluria.

Renal excretion occurs through a combination of glomerular filtration and tubular secretion so the concurrent use of drugs that reduce renal blood flow (e.g. NSAIDs), that are nephrotoxic (e.g. cisplatin) or that are weak organic acids (e.g. aspirin or piperacillin) can delay drug excretion and lead to severe myelosuppression. Particular caution must be exercised in patients with renal insufficiency.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Methotrexate AE

A

Myelosuppression - reversible with leucovorin ‘rescue’

Hepatic fibrosis and cirrhosis

Pneumonitis - characterised by patchy inflammatory infiltrates that regress upon discontinuation of drug

Renal Damage - uncommon. Complication of high dose MTX if clearance is inadequate.

Neurologic Toxicities - with intrathecal administration as it does not normally cross BBB

Teratogenic - due to folate deficiency (neural tube defects) therefore contraindicated in pregnancy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Leucovorin

A

N5-formyl-THF

Antidote to drugs that decrease levels of folic acid (e.g.: MTX) to rescue the bone marrow

Provides normal tissues with the reduced folate, so it circumvents the inhibitor of dihydrofolate reductase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

6-mercaptopurine MOA

A

Antimetabolite

Thio analog of hypoxanthine. Is a prodrug which is converted to Thio-IMP by the salvage pathway enzyme HGPRT:

1) Inhibits the first step of the de novo purine ring biosynthesis
2) Blocks formation of AMP and GMP from IMP
3) Formation of dysfunctional RNA and DNA by incorporation of guanylate analogs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

6-mercaptopurine and 6-thioguanine resistance

A

Patients with Lesch-Nyhan Syndrome will be unresponsive to these drugs as they are prodrugs that need to be converted to their active metabolite by HGPRT.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

6-mercaptopurine PK

A

Metabolised in liver to thiouric acid by xanthine oxidase and excreted by kidneys.

Because allopurinol, a xanthine oxidase inhibitor, is frequently administered to cancer patients receiving chemotherapy to reduce hyperuricemia, it is important to decrease the dose of 6-MP to avoid accumulation of the drug

Also metabolised by enzyme thiopurine methyltransferase (TPMT) –> patients who have weak activity of TPMT are at increased risk for severe toxicities such as myelosuppression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

6-mercaptopurine AE

A

Nausea, vomiting, diarrhoea

Myelosuppression

Hepatotoxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

6-thioguanine MOA

A

Converted to nucleotide TGMP by enzyme HGPRT which then:

1) Inhibits purine synthesis and phosphorylation of GMP to GTP
2) Can be incorporated into RNA and DNA

Allopurinol foes not potentiate 6-TG action because very little is metabolised to thiouric acid (unlike 6-MP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

6-thioguanine Indication

A

Acute nonlymphocytic leukemias

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

6-thioguanine AE

A

Nausea, vomiting, diarrhoea

Bone marrow suppression

Hepatotoxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

6-thioguanine PK

A

Also metabolised by enzyme thiopurine methyltransferase (TPMT) –> patients who have weak activity of TPMT are at increased risk for severe toxicities such as myelosuppression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

5-Flurouracil

A

Antimetabolite: pyrimidine analog

Converted to 5-FdUMP –> inhibits thymidylate synthase (conversion of dUMP to dTMP) –> DNA synthesis is inhibited –> Known as ‘thymineless death’

Also converted to 5-FUTP –> incorporates into RNA –> interferes with RNA processing and function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

5-Flurouracil PK

A

Mainly metabolised by dihydropyrimidine dehydrogenase (DPD)

DPD deficiency seen in up to 5% of cancer patients –> may experience severe toxicity such as myelosuppression, neurotoxicity and life-threatening diarrhea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

5-Fluorouracil/Leucovorin Use and MOA

A

Combination used as chemotherapy for colorectal cancer

5FU inhibits thmidylate synthase by forming a ternary complex (enzyme, substrate (5-FdUMP) + cofactor (N5, N10-methylene-THF/leucovorin)

Increasing levels of N5, N10-methylene-THF potentiates activity of 5FU.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

5-Fluorouracil AE

A

Myelosupression

Hand-food syndrome: an erythematous desquamation of the palms and soles is seen after extended infusions as 5FU accumulates in the merocrine glands

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Capecitabine MOA

A

Antimetabolite. Pyrimidine analog

Orally available prodrug of 5FU

Inhibits thymidylate synthase (conversion of dUMP to dTMP) –> DNA synthesis is inhibited –> Known as ‘thymineless death’

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Capecitabine AE

A

Same as 5FU:

Myelosupression (less than with 5FU)

Hand-foot syndrome: an erythematous desquamation of the palms and soles is seen after extended infusions as 5FU accumulates in the merocrine glands

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Cytarabine MOA

A

Antimetabolite. Pyrimidine analog of deoxycytidine.

Sequentially phosphorylated to the triphosphate –> incorporated into DNA –> incorporated residue inhibits DNA polymerase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Cytarabine PK

A

Not effective orally because of its deamination to the noncytotoxic ara-U by cytidine deaminase in the intestinal mucosa. –> Given IV.

Does not enter CNS. May be injected IT.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Cytarabine AE

A

Severe myelosuppression

Hepatic dysfunction

High doses or IT –> seizures or altered mental states

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Antitumor antibiotics general MOA

A

Bind to DNA through intercalation between bases and block synthesis or new RNA or DNA, cause strand breakage and Interfere with cell replication

Anthracyclines (doxorubicin and daunorubicin) and Bleomycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Anthracyclines MOA

A

Doxorubicin (one of the most widely used anticancer drugs) and daunorubicin: have closely related chemical structures

Are cell cycle nonspecific

1) Inhibition of topoisomerase II
2) Intercalation in DNA –> blockade of DNA and RNA synthesis and strand breakage
3) Binding to cell membranes to alter fluidity and ion transport
4) Generation of free radicals through iron-dependent, enzyme-mediated process

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Anthracyclines AE
Myelosuppression - main dose-limiting toxicity Cardiotoxicity (chronic form) - dose-dependent, dilated cardiomyopathy associated with heart failure - due to free radicals - Iron-chelating agent dexrazoxane can reduce cardiotoxicity All anthracyclines can produce “radiation recall reaction” with erythema and desquamation of the skin observed at sites of prior radiation therapy. Other adverse effects are stomatitis, gastrointestinal disturbances, alopecia.
26
Dexrazoxan
Minimizes adverse events due to anthracycline toxicity (daxorubicin) Iron-chelating agent that reduces cardiotoxicity
27
Bleomycin MOA
Antitumor antibiotic - mixture of glycopeptides Cell-cycle specific - arrests cells in G2 phase DNA-bleomycin-Fe2+ complex undergoes oxidation to bleomycin-Fe3+ --> liberated electrons react with O2 to form free radicals (superoxide, hydroxyl radicals) --> DNA strand breakage
28
Bleomycin AE
Pulmonary toxicity - pneumonitis and pulmonary fibrosis (bleomycin is inactivated by bleomycin hydrolase which is not found in the lungs and skin) Very little myelosuppression
29
Alkylating agents general MOA
Exert cytotoxic effects via transfer of their alkyl groups to various cellular components Alkylation of DNA leads to cell death. Can occur on a single strand or on both strands through corse-linking. Most alkylating agents are bifunctional Cell cycle non-specific but cells are most susceptible to alkylation in late G1 and S phases of the cell cycle, and arrest in G2
30
Alkylating agents general toxicities
Occur mainly in rapidly growing tissues like bone marrow, GI tract and gonads Nausea and vomiting are common: The emetic effects are of CNS origin and can be reduced by pre-treatment with 5-HT3 receptor antagonists like ondansetron or granisetron. Are mutagenic and carcinogenic
31
Mechlorethamine MOA
Nitrogen mustard - alkylating agent --> causes DNA strand breakage Very unstable - solutions must be made up just prior to administeration --> only given IV
32
Mechlorethamine AE
Powerful vesicant = causes painful blisters Severe nausea and vomiting Severe myelosuppression Alopecia Immunosuppression
33
Cyclophosphamide MOA
Prodrug: activated to 4OH-cycylophosphamide by CYP2B Most widely used alkykating agent (a nitrogen mustard) --> alkylation of DNA --> strand breakage --> cell death
34
Cyclophosphamide AE
Hemorrhagic cystitis due to acrolein a toxic metabolite of cyclophosphamide --> prevented with adequate fluid intake (IV hydration) and mesna (reacts with acrolein in bladder) Myelosuppression Sterility Nausea, vomiting, alopecia
35
Melphelan MOA
Nitrogen mustard - bifunctional alkylating agent
36
Melphelan AE
Myelosuppression
37
Carmustine and Lomustine MOA
Nitrosoureas - alkylating agent Require biotransformation, which occurs by non-enzymatic decomposition to alkylating and carbamoylating derivatives Very lipophilic - cross the BBB --> useful in treatment of brain tumours
38
Busulfan MOA
Alkylating agent
39
Busulfan AE
Myelosuppression is main toxicity May cause pulmonary fibrosis
40
Dacarbazine MOA
Alkylating agent Acts as methylating agent after activation in the liver Given IV
41
Dacarbazine AE
Nausea and vomiting Mild to moderate myelosuppression
42
Procarbazine MOA
Converted by liver P450 enzymes to alkylating metabolites Methylate DNA --> DNA, RNA and protein synthesis are inhibited
43
Procarbazine AE
Bone marrow depression Weak MOA inhibitor -> hypertensive reactions may result if given with sympathomimetic agents or tyramine-containing foods Disulfiram-like reactions --> Antabuse --> given to chronic alcoholics as it produces hangover life symptoms as soon as alcohol is taken. It inhibits alcohol dehydrogenase Mutagenic and teratogenic
44
Platinum coordination complexes general MOA
Cisplatin Carboplatin Do not alkylate DNA. Covalently find to DNA and share many pharmacological properties with alkylating agents --> Inhibit DNA synthesis and bind DNA through formation of cross-links Given IV
45
Cisplatin AE
Myelosuppression: mild-to-moderate Ototoxicity Peripheral neuropathy Nephrotoxicity - reduced by hydration and diuresis and with amifostine
46
Amifostine MOA
Cytoprotective agent used to reduce the renal toxicity associated with cisplatin
47
Carboplatin AE
Relatively well tolerated, with less nausea, neurotoxicity, ototoxicity and nephrotoxicity than cisplatin. Dose-limiting toxicity is myelosuppression
48
Vinca alkaloids MOA
Vincristine Vinblastine Microtubule inhibitors --> bind to b-tubulin and inhibit its ability to polymerise with a-tubulin --> cannot form microtubules --> cannot form mitotic spindle --> mitotic arrest in metaphase --> cell division stops --> cells die by apoptosis Cell cycle specific - M-phase Microtubules also have other functions in the cells such as axonal transport, phagocytosis and movement therefore inhibiting microtubules will lead to adverse affects
49
Vincristine AE
Peripheral neuropathy Mild bone marrow depression Alopecia
50
Vinblastine AE
Myelosuppression is dose-limiting Peripheral neuropathy Alopecia
51
Taxanes MOA
Paclitaxel Docetaxel Micrtobule inhibitors --> taxanes bind to b-tubulin subunit of microtubules --> promote microtubule polymerization --> prevent their depolymerisation --> arrests cells in mitosis and leads to apoptosis
52
Paclitaxel AE
Hypersensitivity --> reduced by premedication with dexamethasone, diphenhydramine and an H2 blocker Myelosuppression Peripheral neuropathy Alopecia
53
Docetaxel AE
Myelosuppression - dose-limiting Peripheral neuropathy - not as frequently as paclitaxel Fluid retention - pretreatment with dexamethasone is required to prevent this Alopecia Mucositis
54
Etoposide MOA
Epipodophyllotoxin Inhibits topoisomerase II --> breaks DNA on both strands --> DNA damage through strand breakage Blocks cells in late S-G2 phase
55
Topotecan and Irinotecan MOA
Camptothecins Inhibit topoisomerase I --> which normally breaks DNA on one strand to relieve supercoils --> inhibition results in DNA damage S phase specific
56
Irinotecan AE
Myelosuppression Diarrhea - Early diarrhea occurs within 24 hours after administration, is believed to be due to cholinergic activity, and can be treated with atropine. - Late diarrhea occurs 2–10 days after treatment, and can be life-threatening, leading to significant electrolyte imbalance and dehydration. - Late diarrhea should be treated with loperamide.
57
Prednisone MOA
Glucocorticoid Are lymphocytic --> suppress mitosis in lymphocytes Used to treat acute leukemias and malignant lymphomas Especially effective in the management of autoimmune hemolytic anemia and thrombocytopenia associated with chronic lymphocytic leukemia. This is due to the fact that they increase the number of platelets and red blood cells.
58
Tomoxifen MOA
SERMs --> bind to estrogen receptors and act as agonists or antagonists depending on the tissue Antagonist on breast tissue --> used for receptor positive breast cancer Agonist in non breast tissue - a partial agonist in the endometrium so by giving this drug, estrogen will lead to hyperplasia of the endometrium which can potentially lead to endometrial cancer - agonist on bone --> can prevent bone resorption
59
Tomoxifen AE
Hot flashes Nausea Fluid retention Tamoxifen increases incidence of endometrial cancer
60
Roloxifene MOA
SERMs --> bind to estrogen receptors and act as agonists or antagonists depending on the tissue Antagonist in uterus and breast Agonist on bone --> promotes oestrogen effects in bone to inhibit resorption Used for prevention of postmenopausal osteoporosis and prophylaxis of breast cancer in high risk postmenopausal women
61
Roloxifene AE
Hot flashes Fluid retention
62
Fulvestrant MOA
SERDs --> no estrogen receptor (ER) agonist activity Binds to ER --> inhibits its dimerisation and increases its degradation --> ER-mediated transcription is abolished
63
Aromatase Inhibitors Indication
Aromatase converts androstenedione to estrone In postmenopausal women, this conversion is the primary source of circulating estrogen Aromatase inhibitors are standard of care for adjuvant treatment of postmenopausal women with hormone receptor-postive breast cancer
64
Anastrazole and Letrozole MOA
Non-steriodal Reversible competitive inhibitors of aromatase Aromatase inhibitors are standard of care for adjuvant treatment of postmenopausal women with hormone receptor-postive breast cancer
65
Exemestane MOA
Steroidal Irreversible inhibitor of aromatase Aromatase inhibitors are standard of care for adjuvant treatment of postmenopausal women with hormone receptor-postive breast cancer
66
Androgen Inhibitors Indication
Two types - GnRH agonists and androgen receptor blockers Therapy of prostate cancer - use of GnRH agonists along or in combination with androgen receptors blocker
67
Goserelin and Leuprolide MOA
GnRH agonists GnRH release from hypothalamus is usually pulsatile When given continuously or as a depot, GnRH agonists cause an initial surge in LH and FSH levels followed by inhibiton of gonodotropin release --> testosterone levels fall to 10% of their initial values after a month Initial surge can be counteracted with administration of flutamide for 2-4 weeks
68
Goserelin and Leuprolide AE
Impotence Hot flashes Testicular atrophy
69
Flutamide MOA
Synthetic, nonsteroidal, androgen receptor blocker Metabolised to an active metabolite that acts as a competitive agonist at the androgen receptor --> prevents its translocation to nucleus
70
Imatinib
Inhibitor of Bcr-Abl tyrosine kinase 9:22 translocation - used to treat chronic myelogenous leukemia
71
Transtuzumab
Monoclonal antibody against ErbB2 tyrosine kinase Causes cardiotoxicity - but it is reversible
72
Transtuzumab
Monoclonal antibody against ErbB2 tyrosine kinase Causes cardiotoxicity - but it is reversible
73
Flutamide AE
Gynecomastia Hot flushes Liver dysfunction
74
Asparaginase MOA
Most normal tissues synthesise L-aparagine in amount sufficient for protein synthesis Neoplastic tissue require exogenous course of asparagine Asparaginase hydrolyses serum asparagine to aspartate and ammonia--> deprives tumor cells of asparagine needed for protein synthesis --> cell death
75
Asparaginase AE
Hypersensitivity Decrease in clotting factors: There is an imbalance between coagulation and anticoagulation --> coagulation wins so patients have more thrombotic events than bleeding events Liver abnormalities Pancreatitis --> it can activate pancreatic enzymes Seizures/coma due to ammonia toxicity
76
Hydroxyurea MOA
Inhibits ribonucleotide reductase --> deletion of deoxynucleoside triphosphate pools --> inhibits DNA synthesis Kills cells in S phase Given orally
77
Hydroxyurea AE
Myelosuppression is major toxicity At high doses megaloblastosis unresponsive to vitamin B12 may appear GI symptoms, including nausea, vomiting and diarrhea are common with high doses
78
Interferon a Indication
Hairy cell leukemias, chronic myelogenous leukemias, malignant melanoma and Kaposi's sarcoma
79
Interferon a MOA
IFNa can stimulate NK cells to attack malignant cells Tumor cells can evade the immune system by not producing HLA. IFNa can also increase HLA expression in tumor cells so that the immune cells can attack the cancer cells
80
Interferon a AE
Depression Fever with chills Leukopenia, thrombocytopenia. Fatigue, malaise, anorexia, weight loss, alopecia Transient elevation of liver enzymes.

Pharmacology (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions