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Pharmacology > 44_Chemotherapy Drugs > Flashcards

44_Chemotherapy Drugs Flashcards

1
Q

What are the 4 classifications of Cytotoxic Drugs

A
  1. DNA Interactive Agents
  2. Antimetabolites
  3. Tubulin Interactive Drugs
  4. Misc
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2
Q

What are the DNA Interactive Agents?

A 
Alkylating Agents
Heavy Metals (Platinums)
DNA Strand Breakage (Bleomycin)
DNA Topo I Inhibitor (Irinotecan)
DNA Topo II Inhibitor 
  -Intercalators (Anthracyclines, Anthracenes)
  -Podophiles (Etoposide)
DNA Minor Groove Binder (Plicamycin)
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3
Q

What are the Alkylating Agents?

A

Mechlorethamine (Nitrogen Mustard)
Estramustine (Estrogen Nitrogen Mustard)
Nitrosurea (Carmustine, BCNU)
Cyclophosphamide & Ifosfamide

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4
Q

What is significant about Nitrosureas, and what are the two types?

A

They can cross the BBB and have delayed myelosuppression. They are Carmustine & BNCU

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5
Q

What is the MOA of alkylating agents?

A

Intra or Interstrand cross linking
Alter the structure of the bases so that there is:
-No enzyme repair
-Miscoding of the nucleotides

Transfer alkyl groups to cellular components (2 ways)

  1. Covalent binding of alkyl groups to N-7 on guanine base
  2. Alkylating agents are bifunctional so they can add an alkyl group to 2 DIFFERENT MOLECULES. This is how they cross link DNA
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6
Q

What kind of drug is Cyclophosphamide and what are its SEs?

A

It is a DNA Interactive Alkylating Agent

It is a prodrug activated by the PY450 system into cytotoxic components (incl arolein and a mustard). Widely used, high oral bioavailability

SEs:
Myelosuppression
Cystitis w/ Hemorrhage
SIADH

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7
Q

What is the cause and how is the hemorrhagic cystitis overcome with the use of cyclophosphamide or Ifosfamide?

A

The cause is the metabolite acrolein depositing on the walls of bladder and renal tubules

Mesna can prevent this. Also drink a ton of water and educate the patient.

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8
Q

What kind of drug is Ifosfamide and what are its SEs?

A

It is a DNA Interactive Alkylating Agent

It is a prodrug activated by the PY450 system

SEs:
Myelosuppression
Cystitis w/ Hemorrhage
Central Neurotoxicity (cyclophosphamide doesn’t)
- mental status changes, somnolence, coma, death
Metabolic Acidosis

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9
Q

How can the SEs of Ifosfamide be overcome?

A

Hemorrhagic Cystitis - Mesna
Patient Hydration and urination
Bicarb for the Metab Acidosis

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10
Q

What kind of drug is Dacarbazine and what are its SEs?

A

It is a DNA Interactive Alkylating Agent

Has CNS Penetration, BUT USED FOR MELANOMA not brain cancer. Why? Because melanoma typically metastasize to the brain

SEs:
SEVERE N/V
Vesicant
Myelosuppression
Anaphylaxis (rare)
Hepatotoxicity (rare)

Co-Rx with Anti-emetics bc this causes some serious N/V

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11
Q

What kind of drug is Temozolomide and what are its SEs?

A

IT is an DNA Interactive Alkylating Agent

Has CNS Penetration, same family as Dacarbazine

Myelosuppression
N/V
Constipation
Diarrhea

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12
Q

What are some guidelines for taking Temozolomide?

A

Take on empty stomach so it can be absorbed better
Co-Rx with an anti-emetic
Do not open or chew the capsules
PCP (pneumocystis pneumonia) prophylaxis with chemoradiation

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13
Q

What kind of drug is Cisplatin and what are its SEs?

A

It is a DNA Interactive Heavy Metal

Binds to and cross links DNA

SEs:
Severe N/V
Nephrotoxic (renal damage reduced with mannitol and forced hydration; DDI w/nephrotoxic drugs)
Neurotoxicity (periph and acoustic nerve damage)

Always give an anti-emetic with this!!!

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14
Q

What are SEs of alkylating agents?

A

SEs
Tend to occur in rapidly growing tissues i.e.
- Bone Marrow (dose dependent)–>Myelosuppression
- GI Tract: N/V very common

Vesicant Effect
- Local tissue injury at injection site (necrosis if it leaks out the vein)

Carcinogenic
- Can occasionally induce AML

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15
Q

What can alkylating agents sometimes induce?

A

AML

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16
Q

What are the other bis(chloroethyl)amine Alkylating Agents?

A

Mechlorethamine
Chlorambucil
Melphalan

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17
Q

What kind of drug is Carboplatin and what are its SEs?

A

DNA Interactive Heavy Metal

Binds to and Cross Links DNA

SEs:
Less GI & Renal Toxicity (but DDI with nephrotoxic drugs)
Myelosuppression
N/V

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18
Q

What kind of drug is Oxiplatin and what are its SEs?

A

DNA Interactive Heavy Metal

SEs:
Neurotoxic (peripheral neurotoxicity)
Myelosuppression (Neutropenia)
Anaphylactic Rxn

Avoid the cold!! Cold drinks, gloves to open the refrigerator

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19
Q

What kind of drug is Topotecan and what are its SEs?

A

DNA Interactive, Topo I Inhibitor (Camptothecin)

Causes DNA Damage so no replication

RENAL ELIMINATION

SEs:
Myelosuppression
Diarrhea

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20
Q

What kind of drug is Irinotecan and what are its SEs?

A

DNA Interactive, Topo I Inhibitor (Camptothecin)

Causes DNA damage so no replication

Activated by liver (CYP3A4), excreted in bile and feces

SEs:
Myelosuppression
Diarrhea
  -Acute treat with Atropine
Mucositis
N/V

Genomic Marker is UGT1A1, if u have it then increased risk of toxicity

Homozygous for UGI1A1 allele also has higher risk of toxicity

21
Q

What are the Intercalating Topo II Inhibitors?

A

Anthracyclines:

  • Doxurubicin
  • Daunorubicin
  • Idarubicin
  • Epirubicin
  • Valrubicin

Anthracendione
-Mitoxantrone (green urine due to blue discoloration)

22
Q

What are the non intercalating DNA Topo II Inhibitors?

A

Podophyllotoxins (herbal)

  • Etoposide
  • Teniposide
23
Q

What is the MOA of Anthracyclines? What are there general SEs?

A

They generate free radicals which cause DNA damage, intercalate in btwn base pairs and inhibit topo II

SEs

  • CARDIOTOXICITY
    • Important class effect toxicity
    • ECG Abnormalities/Arrythmias
    • Dose Dependent cardiomyopathy –>CHF
  • Red/Orange Urine
  • Myelosuppression
  • N/V
  • Radiation Recall

Note: The max dose is over a lifetime bc the cardio effects are additive over a lifetime

24
Q

How can cardiotoxicity from the anthrocyclines be overcome?

A

Dexrazoxane

Iron chelator that inhibits free radical formation caused by iron

btw, liposomal formulations may be less cardiotoxic

25
Q

What are the liposomal formulations of the Anthracyclines, and what are their properties and SEs?

A

Daunorubicin citrate Liposome
Doxorubicin HCL Liposome

Properties:
Longer half life
Increased exposure to target sites

SEs
Hand foot syndrome
Decreased Cardiotoxicity
No vesicant effect

26
Q

What is the MOA of podophyllotoxins, SEs, what are the drugs?

A

MOA: Inhibit Topo II so no DNA unwinding/winding–>DNA damage

Most active during late S and early G2 phase of cell cycle

SEs:
N/V
Myelosuppression
Alopecia
Infusion related reactions (give diphenhydramine)
HypoTN

Drugs:
Etoposide
Teniposide

27
Q

What are the folate antagonists?

A

Antimetabolite

Methotrexate
Pemetrexed

28
Q

What are the purine antagonists?

A

Antimetabolite

6-Mercaptopurine (6-MP
6-Thioguanine (6-TG)
Fludaribine)
(Cladribine)

29
Q

What are the pyrimidine antagonists?

A

Antimetabolite

Fluoropyrimidines

  • 5-FU
  • Capecitabine

Deoxycytidine Analogs

  • Cytarabine (Ara-CTP)
  • Gemcitabine
30
Q

What is the MOA of the antimetabolites?

A

Interfere with intermediary metabolism so that cancer cells CANT PRODUCE DNA so can’t proliferate.
-Expect toxic effects related to rapidly dividing normal tissues from this class

31
Q

What kind of drug is 5-FU and what are its SEs?

A

Pyrimidine Antagonist specifically Fluoropyrimidine

Given IV, can penetrate CSF
Inhibits thymidylate synthesis and leads to “thymineless” cell death. In the cell 5-FU is converted to 5-FdUMP, then incorporated into DNA. DNA can’t live with that shit

SEs:
Myelosuppression
Mucositis
Diarrhea

32
Q

What kind of drug is Capecitabine and what are its SEs?

A

Pyrimidine Antagonist specifically Fluoropyramidine

Good Oral Bioavailability

SEs
Mucositis
Diarrhea
Hand Foot Syndrome
Myelosuppression
33
Q

What kind of drug is Gemcitabine and what are its SEs?

A

Pyrimidine Antagonist specifically Deoxyctidine

Look like CDP & CTP
Inhibits DNA Polymerization & Repair
Incorporated into DNA, terminating the chain

SEs:
Meylosuppression
Skin Rash
Diarrhea
HUS
34
Q

What kind of drug is Cytarabine and what are its SEs?

A

Pyrimidine Antagonist specifically deoxycytidine

Activated by kinases: Cytarabine–>(kinase)–>Ara-CTP
Polymerase is blocked by Ara-CTP

MOST SPECIFIC FOR THE S PHASE

Can be used at LOW (for long time) OR HIGH DOSES (over short periods of time)

SEs at low doses:
Myelosuppression
Mucositis
Diarrhea
Flu-like syndrome (Cytarabine syndrome)

SEs at higher dose:
Conjuctivitis
Cerebellar Syndrome (ataxia, slurred speech, nystagmus)
Increased LFTs

35
Q

What kind of drug is Methotrexate and what are its SEs?

A

Folate Antagonist

Looks like folic acid. Inhibits DHF reductase
-thymidylate and purine synthesis is inhibited

Renal excretion so adjust in renal disease
Some drugs compete for excretion
-ASA, NSAIDs, PCN, cephalosporins

SEs:
Mucositis
GI: Diarrhea
Myelosuppression

36
Q

How can the cytotoxic effect of Methotrexate on normal cells be reduced?

A

Leucovorin rescue

Taken up more readily by normal cells than neoplastic cells
bypasses the DHF reductase step so can go straight into the reaction

37
Q

What kind of drug is Pemetrexed and what are its SEs?

A

Folate Antagonist similar to methotrexate

Used in mesothelioma

SEs:
Myelosuppression so bad have to give folic acid and B12 with it
Rash
Stomatitis
Increased AST/ALT
38
Q

What is the MOA of purine antagonists?

A

Activated into toxic nucleotides by HGPRTases that block purine synthesis

39
Q

What kind of drug is 6-Mercaptopurine (6-MP) & 6-Thioguanine (6-TG) and what are its SEs?

A

6-MP is related to azathioprine (immunosuppressant)

USING THIS WITH ALLOPURINOL (or febuxostat) WOULD RAISE 6-MP LEVELS!! So if on that medicine, reduce the dose of 6-MP. Its bc 6-MP is metabolized by XANTHINE OXIDASE and allopurinol and febuxostat are both Xanthine oxidase inhibitors.

6-MP & 6-TG both activated by hypoxanthine-guanine phosphoribosyltranferases aka HGPRTases that turn them into toxic purines

Both have low bioavailability due to FIRST PASS METABOLISM

40
Q

What are the Tuberlin Interactive Agents?

A

Microtuble formation Inhibition:

  • Vincristine, Vinblastin, Vinorelbine
  • Vinca Alkaloids

Keeps the tubulin polymerized so that the spindle can’t deconstruct

  • Paclitaxel, Docetaxel, Ixabepilone
  • Taxanes
41
Q

What is the MOA of vinca alkaloids?

A

Inhibit tubulin polymerization. This results in arrest of mitosis (SO THIS IS M-PHASE SPECIFIC)

42
Q

What are the SEs of the Vinca Alkaloids Vincristine, Vinblastine, and Vinorelbine?

A

Vincristine

  • Periph Neuropathy (PN)
  • Mild N/V
  • Only one in this class that doesn’t have Myelosuppression

Vinblastine

  • PN
  • Myelosuppression
  • N/V

Vinorelbine (semi-synthetic from vinblastine)

  • Myelosuppression
  • PN
43
Q

What are the acute toxicities of paclitaxel? Chronic? Other significant SEs?

A

Acute: N/V, HypoTN, arrythmias
Chronic: Myelosuppression, Neuropathy
Others:
-HSR, pretreat with antihistamines or corticosteroids
-Albumin bound paclitaxel
-Abraxane has less hypersensitivity reactions and less bone marrow toxicity

44
Q

What drug has less HSRs and bone marrow toxicity than Paclitaxel?

A

Abraxane

45
Q

What are the SEs for docetaxel?

A

Anaphylactoid
Myelosuppression
Edema

46
Q

What is Rituximab and its SEs?

A

Monoclonal Ab that targets CD20 on B cells. Induces complement mediated lysis, direct cytotoxicity, and induction of apoptosis

Use for non Hodgkins

SEs:
Infusion related reaction so give tylenol and diphenhydramine
Myelosuppression
Tumor Lysis syndrome
Avoid live viral vaccination
Can get Hep B reactivation with fulminant hepatitis
Ab formation

47
Q

What are the growth factor receptor inhibitors?

A

Monoclonal Abs

  • Trastuzumab
  • Cetuximab
  • Panitumumab

Inhibitors of EGFR tyrosine kinase domain

  • Gefitinib
  • Erlotinib

Angiogenesis Inhibitors

  • Bevacizumab
  • Sorafenib
  • Sunitinib
48
Q

What drug is a Her2 Inhibitor? What are its SEs?

A

Trastuzumab

For breast cancers that over express Her2/neu receptor for epidermal growth factor

DO NOT GIVE WITH DOXORUBICIN

Why? B/c trastuzumab causes cardiotox, and can lead to CHF.

SEs:
Cardiotox
Infusion Rxn

49
Q

What are the two Her-1 Inhibitors? What are the SEs?

A

Cetuximab and Erlotinib

Cetuximab is directed to extracellular domain of EFGR

Erlotinib inhibits tyrosine kinase domain of EGFRs (don’t smoke with this, take on empty stomach, avoid antacids, H2 blockers, PPI, grapefruit juice

SEs: Cetuximab

  • Infusion Rxn
  • Abn e-lytes
  • Rash, Photosensitivity

SEs: Erlotinib

  • Diarrhea
  • Rash
  • Lung Disease

Pharmacology (17 decks)

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