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Anti-Neoplastics
Pharm Exam 2
138
Pharmacology
Post-Graduate
02/27/2010

Additional Pharmacology Flashcards

 


 

Cards

Term
What is meant by Cell Cycle Specific (CCS) ?
Definition
It means the drug will ONLY target cells that are dividing
Term
What is meant by Cell Cycle Non-Specific?
Definition
It means that drugs will target BOTH dividing & non-dividing cells
Term
What is the over all concept of Log-Kill
Definition
It means that drug or irradiation therapy kills at a constant PROPORTION of cells not a fixed number
Term
What are the 4 principles of combination therapy
Definition

1) Use drug that targets a single activity against the specific tumor

2) Each drug should have a different MOA and act a different cell cycle phase

3) When possible choose drugs that don't have overlapping toxicity

4) All drugs should be used at optimal dose and most effective scheduling in combination

Term
What are the 5 drugs that need to be activated within the body  before they enter S phase?
Definition

Cytarabine

Fluorouracil

Mercaptopurine

Methotrexate

Thioguanine

Term
What is Cytarabine converted to in the body?
Definition
Cytidine Monophosphate
Term
What is Flourouaracil Converted to in the body?
Definition
ribosyl & deoxyribosyl nucleotide
Term
Mercaptopurine is converted to?
Definition
6 thioinosinic acid
Term
Methotrexate is converted to what in the body?
Definition
polyglutamated methotrexate
Term
What is Thioguanine converted to in the body?
Definition
Nucleotide
Term
What part of the Cell Cycle does Antimetabolites Target?
Definition
S-phase
Term
What part of the Cell Cycle does Podophyllotoxins Target?
Definition
S-Phase & G2
Term
What part of the cell cycle does Antimutatic & Vinca Alkaloids Target
Definition
M-Phase
Term
What occurs during S-phase
Definition
DNA Synthesis
Term
What occurs during G2 Phase?
Definition
Synthesis of components needed for mitosis
Term
What occurs during G1 Phase
Definition
Synthesis of components needed for DNA Synthesis
Term
What kind of drugs are best for fast growing tumors (High % of cancer cells)
Definition
CCS
Term
What kind of drugs are good/ more effective toward Slow growing tumors (low % of cancer cells)
Definition
CCNS
Term
What does the antimetabolite drugs target?
Definition
The Enzymes
Term
What are the antimetabolite drugs
Definition

Methotrexate

5' Fluorouracil

Capecitabine

Term
What are the alkylating agent drugs
Definition

Cyclophosphamide

Carmusitine

Temozolamide

Cisplatin

Term
What drugs are the cytotoxic Antibiotics
Definition

Daunorubicin

Doxorubicin

Dactinomycin

Bleomycin

Term
What are the Vinca Alkaloids
Definition

Vincristine

Vinblastine

Term
What are the Epipodophyllotoxins
Definition
Etoposide
Term
What are the camptothecins?
Definition
Topotecan
Term
What are the Taxanes?
Definition
Paclitaxel
Term
What is the general class that consists of Vina Alkaloids, Epipodophyllotoxins, Camptothecins, & Taxanes?
Definition
Natural Products
Term
What is the Antiestrogen drug?
Definition
Tamoxifen & Fulvestrant
Term
What is the aromatase inhibitor?
Definition
Anastrazole
Term
What is the DHT synthesis inhibitor?
Definition
Finasteride
Term
What is the antiandrogen drug?
Definition
Flutamide
Term
What is the Gonadotropin releasing hormone drug?
Definition
Leuprolide
Term
What are the Adrenocorticosteroids?
Definition
Prednisone & Prednisolone
Term
What drugs falls under the ENZYME class?
Definition
Asparaginase
Term
What are the Monoclonal Antibodies?
Definition
Rituximab & Trastuzumab
Term
What drug is considered a Platinum Coordination Complex?
Definition
Cisplatin
Term
What is the MOA of Cytarabine?
Definition
Blocks DNA strand Elongation
Term
What kind of toxicity does cytarabine display
Definition
Neurotoxicity
Term
What is the MOA for Capecitabine? What is it converted to in the body?
Definition
Inhibits thymidylate synthase. Converted to 5' Fluorouracil.
Term
What is the MOA of Etoposide?
Definition
Stabilizes Topo II; causeing breaking of dbl strands during replication
Term

What is the dose-limiting effect of etoposide?

 

Definition
WBC's, causing leukopenia
Term

What is Etoposide used to treat?

 

Definition
First time & metatastic testicular cancer
Term
What is the MOA of Topotecan?
Definition
Topo I inhibitor; prevents re-ligation of helix which cause accumulation of ssDNA.
Term
What is the dose limiting effect of Topotecan?
Definition
Neutropenia, thus pt at risk for infection
Term

What is Fulvestrant use to treat?

 

Definition
Hormone-sensative tumors
Term
What is the MOA of Fulvestrant?
Definition
A Nonsteroidal Androgen Antagonist that inhibits the translocation of steroid receptors to the nucleus
Term
What is the MOA of Finasteride?
Definition
5-alpha-reductase inhibitor that inhibits synthesis of DHT
Term
What are Flutamide and Fulvestrant used to treat?
Definition
Prostate Cancer
Term
What is Leuprolide's MOA?
Definition
A GnRH analogue partial GnRH agonsist that inhibits FSH & LSH release
Term
What is Leuprolide used to treat?
Definition
Prostate Cancer
Term
What is the MOA of rutiximab?
Definition
An antiCD20 monoclonal antibody that binds to the CD20 antigen on B-cells
Term
What kinds of cancers is rituximab use to treat?
Definition
Non Hodgkins Lymphoma
Term
What is the MOA of Hydroxyurea?
Definition
It inhibits Ribonucleotide reductase, stopping the converion of ribonucleotides to deoxy ribonucleotids
Term
What is Hydroxyurea use for?
Definition
Myelproliferative Disorders
Term
What is the MOA of Imatinib Mesylate?
Definition
Inhibits bcr-abl tyrosine kinase which is found in CML
Term
What is the MOA of Methotraxate?
Definition
Blocks the enzyme DHFR; preventing Dihydrofolate to go to Tetrahydrofolate, as well as preventing Folate to go to Dihydrofolate
Term
What is the use of Methotrexate
Definition

Solid Tumors (i.e. choriocarcinoma or osteosarcoma)

ALL (Acute Lymphoblastic Leukemia

Term
What is the Antidote for Methotrexate?
Definition
Leucovorin; Binds to DHFR in normal cell better then cancer cells and provides a bolus of 1 Carbon unit source to restore synthesis of purine/pyrimadine causing resumption of DNA synthesis
Term
What is the Toxic Effects of Methotrexate?
Definition

Nephrotoxic

Myelosuppressive (neutropenia, thrombocytopenia, diarrhea)

Pulmonary Toxicity and Hepatotoxicity with long-term use

GIT-mucositiis

Term
What is the effective use of G-CSF (granulocyte growth factor)?
Definition
Its use has shortened the period of Leukopenia after high dose chemo
Term
What is the MOR (mech of resistance) by the cancer cells to methotrexate?
Definition

Reduced polyglutamation

Change in receptor affinity

increase DHFR levels

Term

What is the MOA of 5' Flourouracil?

 

Definition

Interferes with RNA function by misincorporating the fluorodinated uridine into RNS; this creates a dysfunction RNA

Also, inhibits Thymidylate Synthase thus blocking DNA synthesis

Term
What is the use of 5' Fluorouracil?
Definition
Pancreatic Cancer, Breast Cancer (Metastatic)
Term
What is the Toxic Effects of 5' FU?
Definition

Anorexia/nausea

Alopecia

Stomatitis/Diarrhea

Myelosuppression in bolus doses

Term
What is the MOR of cancer cells to 5'FU?
Definition
Changing the sensitivity of the enzyme to the drug
Term
What is the MOA of Cyclophosphamide?
Definition
Prodrug concerted to an active mustard  that interfers with transcription and translation
Term
What is the Toxicity of Cyclophosphamide?
Definition

Myelosuppression

Permanent Amenorrhea & azoospermia

Leukemogenic

Cardiotoxic in high doses

Renal & Bladder toxicity

Term

What is the end product of metabolism for Cyclophosphamide?

 

Definition

Active nitrogen mustard (very Nephrotoxic)

&

Acrolein ( causes hemorrhagic cystitis)

Term
What is the Antidote for Clyclophosphamide?
Definition
Mesna; it conjugates toxic metabolites i.e. Acrolein, in the urine to help reduce they cystitis
Term
What is cyclophosphamide effect on water?
Definition

Causes Inappropriate secretion of ADH so may cause water intoxication. Also the drug is given with 3 liter of fluid a day to protect the kidney.

With all the water Hyponatremia can result; if this occur fuid intake is decreased.

Term
What is the antidote to aid in the Excess Water Overload that can be caused by Cyclophosphamide?
Definition
Demeclocycline; this blocks the ADH effect
Term
What is the significance of Temozolamide?
Definition
Sucess in treating Malignant Gliomas
Term
What is the MOA of Doxorubicin?
Definition

Intercalates with DNA and bind the helical groove

Prevents Topo II from resealing breaks

Cause Free- Radical formation

Term
What is the uses of Doxorubicin?
Definition

Solid breast, endometrial, testes, & lung tumors

Hodgkins & Non-Hodgkins

Term
What is the MOR of the cancer cells to Doxorubicin?
Definition

Development of abnormal transport protein

MDR gene over-express the glycoprotein regulating pump-out

Term
What is the Route of Admin for Doxirubicin?
Definition

Fast-running IV

 

*Risk of extravasation

Term
What is the Antidote for Doxorubicin against extravasation.
Definition
Dimethyl Sulphoxide
Term
What is the Toxic Effect of Doxorubicin?
Definition

Cardiomyopathy

Suprventricular Arrhythmia w/ repeated doses

 

*Given with Azathioprine enhances its toxicity and cholestasis may occur

 

 

Term
What is the Antidote use with Doxirubucin against the cardiomyopathy?
Definition
Dexrazoxane - an iron chelator
Term
What is the MOA of Daunorubicin?
Definition
Same as Doxirubicin
Term
What is Daunorubicin used for?
Definition
Leukemia
Term
What are the toxicities of Daunorubicin?
Definition
Same as Doxi, but Dauno may cause Red Urine
Term
What is the MOA of Dactinomycin?
Definition

Bind to DNA helix

Prevents transcription of DNA by RNA polymerase

Cause single strand breaks in DNA

Term

What are the Uses of Dactinomycin?

 

Definition

Rhabdomyosarcoma

Wilms Tumor

Ewings Tumor

Kaposi sarcoma

Term
What is the Toxic Profile of Dactinomycin?
Definition

Hematopoietic suppression

Pancytopenia-dose Limiting property

 

Others: Diarrhea, glossitis, cheilitis and oral ulcers, alopecia, anorexia, n/v

Term
What is the MOA of Bleomycin?
Definition

Causes DNA fragmentation

Free-Radical Formation causes chromosomal fragmentation

Cells accumulate in G2 Phase

Term
What are the uses of the Bleomycins?
Definition

Testicular

Squamous carcinoma of head, neck, & lungs

Lymphomas

Term
What is the toxic effect of Bleomycins?
Definition

Pulmonary Toxicity (dry cough)

Pulmonary Fibrosis

 

Others: little myelosuppression, hyperthermia in lymphoma pts especially, skin blisters, pigmentation, hyperkeratosis

Term
What is the MOA of Vinblastine & Vincristine?
Definition

Spindle Poisons; they bind to tubulin and prevent assembly of microtubules.

They act in M phase of the cycle

Term
What is the use of Vincristine?
Definition

Peds leukemia

Solid Hodgkins diseases

Rhabdo

Lymphomas

Neuroblastomas

Term
What is the uses of Vinblastine?
Definition

Hodgkins

Testicular carcinoma

Term
What is the toxic effect of Vincristine?
Definition

Neurotoxic (peripheral & autonomci neuropathy)

Sensory & Motor parasthesis

 

*Bone marrow spearing

Term
What is they toxic effect of Vinblastine?
Definition

Myelotoxic - reversible

Dose-Limiting Neutropenia

Leucopenia & Alopecia

Term
What is the MOR of the cancer cells against Vincristine/blastine?
Definition
MDR gene mutation
Term
What is the MOA of Etoposide?
Definition

Topo II stabilizer; cause dsDNA breaks during replication.

Specific for late S and early G2 phase.

Term
What are the uses of Etoposide?
Definition

Testicular Cancer

Hodgkins

Diffuse Lymphoma

Oat cell

Term
What are the Toxic Effects of Etoposide?
Definition

Dose-Limiting Leukopenia

May cause AML development

 

Others: Hypersensitivity, Hepatic & renal toxicity @ high dose, Neuromuscular & Skeletal toxicities

Term
What is the Toxic effects of Topotecan?
Definition

Dose Limiting- Neutropenia, thrombocytopenia

Dose-Limiting Mucositis & Diarrhea in pts with hematological malignancies

Term
What is the MOA of Paclitaxel?
Definition
Inhibits microtubule disassembly and microtubular plates accummulate in the cells causing abnormal and dysfunctional spindles
Term
What is the use of Paclitaxel?
Definition

Primarily used to treat advanced ovarian and metastatic ovarian cancer

Breast Mets

Lung, esophageal, bladder, head and neck cancers

Term
What are the toxic effects of Paclitaxel?
Definition

Hypersensitivity rxn

severe but reversible neutropenia

Cardiac conduction defects

alopecia

n/v

PERIPHERAL NEUROPATHY

 

*Clearance reduced by Cisplatin

Term
What is the MOA of Tamoxifen?
Definition
A Selective Estrogen receptor modulator
Term
What is Tamoxifen used to treat?
Definition

Breast cancer and PROPHYLAXIS

Given to pt who had chemo, radiation, or surg

Given to older women to shrink tumors that are inoperable

 

Infertility, gynecomastia

 

Term
What is a risk with long-term use of Tamoxifen?
Definition
Endometrial Cancer
Term
What are the toxic effects of Tamoxifen?
Definition

N/V

Hot Flashes

Vag bleeding,

hypercalcemia

ocular dsyfunc

peripheral edema

Term
What is the MOA of Fulvestrant?
Definition
Pure estrogen receptor antagonists!
Term
What its Fulvestrant used for?
Definition

Treatment in women with breast cancer which have become resistant to Tamoxifen

Only give to Post-menopauseal women.

Given IM monthly

Term
What is Anastrozole and its MOA?
Definition
It is an aromatase inhibitor that prevents synthesis by inhibitin aromatase enzyme. So estrogen cannot be made at all because androstene dione does not get converted to estradiol
Term
What is anstrozole's use?
Definition
Also used to replace tamoxifen
Term
What is Flutamide?
Definition
An antiandrogen; Nonsteroidal androgen antagonists.
Term
What is Flutamide's MOA?
Definition
Inhibits the translocation of steroid receptors
Term
What is Flutamide used for?
Definition
Prostate Cancer or BPH
Term
What is Leuprodile's MOA?
Definition
It is a GnRH analogue that acts as a partial agonist at GnRH receptors
Term
How does Leuprodil work to inhibit LH and FSH?
Definition
The analogue is released in a constant dose, as oppose to the usual pulsatile secretion that GnRH performs, this maintains constant blood levels and inhibits the release of LH & FSH
Term
When is Leuprolide used?
Definition
In Prostatic carcinoma
Term
What is the Toxic effect of leuprolide?
Definition

Bone pain & Back pain

gynecomastia

hematuria

Impotence

Testicular atrophy

 

*Can cause hypogonadism!!!!!

Term
What is the MOA of aspariginase?
Definition
It deprives the cancer cell of aspariginine so that it cant be used for protein synthesis
Term
What is the toxicity of Aspariginase?
Definition

Hypersensitivity rxn

High levels (Precipitate coma)

Clottin abnormalities

Intracranial Hemmorrhage (rare, within first week of tx)

Term
What is the toxicity of Trastuzumab?
Definition

N/V

Chills

Fevers

Headaches

Ventricular dysfunction & heart failure association

Term
What kind of tumors are EGFR family associated with?
Definition
Breast, Lung, glioblastoma, head, neck, bladder, colerectal, ovarian, and prostate
Term
WHat is the MOA of Cisplatin?
Definition
Breaks in DNA strands b/c replace Chloride with water
Term
What kind of needles should not be use when adminstering Cisplatin?
Definition
Aluminum because aluminum reacts with the drug and inactivates it.
Term
What cancers are treated with Cisplatin?
Definition
Urogenital, testicular, ovarian, & Bladder
Term
What are the toxic effects of Cisplatin?
Definition

Nephrotoxicity

Electrolyte disturbance (decrease in them)

Ototoxicity

*Marked N/V (reduced by given Ondansetron=antiemetic)

Term
What agents are likely to cause neutropenia?
Definition
Alkylating agents, anthracyclines, Taxanes, & Topo inhibitors
Term
What agent most likely to cause ARF?
Definition
Cisplatin
Term
What agent most likely to cause Acute or Chronic cardiomyopathy
Definition
Anthracyclines (doxorubicin), 5'FU, Trastuzumab
Term
What agent cause respiratory issues?
Definition
Bleomycin
Term
What agent causes bladder issues?
Definition
Cyclophosphomide- hemorrhagic cystitis
Term
What agent most likely to cause Hand-foot syndrome?
Definition
5'FU infusional, capecitabine
Term
Agent causing anaphylaxis?
Definition
Taxanes
Term
Agent causing Alopecia, fatigue, lathargy?
Definition
Combos with alkylating agents
Term

What drugs DO NOT exhibit dose-limited toxicity to bone marrow!

 

 

*No myelosuppression

Definition

Hormones

Vincristine

Bleomycin

Asparaginase

Cisplatin

Term
What drugs are associated with Cardiac toxicities?
Definition

Common & serious: Doxorubicin and other anthracyclines

 

Not so common: Paclitaxel, Trastuzumab, & 5'FU= Angina and MI

Term
Drugs with Neurotoxicity?
Definition

Cytarabine

Asparaginase

Vincristine

Cisplatin

Flourouracil

Methotrexate

Term

Dose-Limiting Toxicities- Match:

1) Methotrexate

2) Cisplatin

3) Doxorubicin

4) Daunorubicin

5) Bleomycin

6) Vincristine/blastine

7) Etoposide

8) Topetecan

Definition

1) Myelotoxic

2) Kidney

3) Cardiac

4) Cardiac

5) Pulmonary

6) Neurologic

7) Leukopenia

8) Neutropenia & thrombocytopenia

Term
Which drugs shoe the most and least vomiting effects?
Definition

Most- Cisplatin

Least - Vinca alkaloids

Term
Which drugs shto the most and least Alopecia?
Definition

Most- alkylating agents

Least - antimetabolites

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