Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

IHO Block 3 > Drugs that Disrupt DNA > Flashcards

Drugs that Disrupt DNA Flashcards

1
Q

What groups do drugs that disrupt DNA fall into?

A
  1. Crosslinking agents (alkylating agents & misc. others)
  2. Intercalating agents (esp. anthracycline antibiotics)
  3. Drugs that cause Strand Breaks/Prevent Replication
    - -These drugs fall into several chemical classes including alkylating agents, natural products (antibiotics and plant alkaloids) and misc. drugs.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is hemorrhagic cystitis (toxicity) unique to?

A

Cyclophosphamide

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

What chemical class of agents is associated with cardiomyopathy?

A

Anthracycline antibiotics (doxorubicin)

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

What do most drugs that disrupt DNA cause (side effects)?

A

-Bone marrow suppression
-Gastritis
-Alopecia
(bc these drugs target rapidly dividing cells)

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

Are cross linking agents CCS?

A

NO - CCNS - reactions that initiate cell death can occur at any time but primary toxicity occurs at late G1 and S phase
-However, they are dependent upon proliferation

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

Which alkylating agents are converted to a strong electrophile fast?

A

MECHLORETHAMINE - virtually instantaneous

-Given IV to minimize blistering and GI effects

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

What alkylating agents are converted to a strong electrophile slowly?

A

BUSULFAN, CYCLOPHOSPHAMIDE, IFOSFAMIDE, MELPHALAN

  • Must be activated in the liver and other tissues
  • Can be given orally!
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the anthracycline antibiotic?

A

Doxorubicin!

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

What is important about doxorubicin?

A
  • CCNS drug
  • Intercalates DNA
  • Major toxicity is unusual cardiomyopathy that is often irreversible and related to the total dose of the drug
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is important about Bleomycin?

A
  • Unique MOA and spectrum of toxicities
  • Included in many combination therapies
  • Generates free radicals that cut through DNA strands
  • Does not cause significant myelosuppression (unlike other drugs)
  • It does cause skin and lung damage – because those tissues do not have the enzyme (hydrolase) required to metabolize BLEOMYCIN.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the three functional grouping of drugs that disrupt DNA?

A
  1. Drugs that crosslink DNA (esp. alkylating agents)
    - includes alkylating agents, natural products (antibiotics) and misc.
  2. Drugs that intercalate and form adducts with DNA
    - natural products (esp. anthracycline antibiotics)
  3. Drugs that cause strand breaks
    - natural products (antibiotics and plant alkaloids) and misc.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the three chemical types of cross-linking agents?

A
  1. Alkylating agents
  2. Antibiotics
  3. Misc.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the two groups of alkylating agents?

A
  1. Nitrogen mustards

2. Nitrosoureas

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

What are the nitrogen mustards we need to know?

A

(discovered due to bone marrow suppression seeing soldiers after being exposed to mustard gas)
-Chlorambucil, Cyclophosphamide, Ifosfamide, Mechlorethamine (not used much anymore - often causes cancer), Melphalan

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

What are the nitrosoureas you need to know?

A

Carmustine (BCNU), Lomustine (CCNU)

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

What antibiotic cross-linker should you know?

A

Mitomycin

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

What misc. cross linkers should you know?

A

Carboplatin, cisplatin, oxaloplatin, BUSULFAN, DACARBAZINE, PROCARBAZINE, TEMOZOLAMIDE

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

What is the mechanism for alkylating agents?

A
  1. Drug activation
  2. N7 guanine - Neutrophilic attack
  3. DNA Damage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How are alkylating agents selectively toxic?

A
  • 50% of human cancers have a mutation in p53, so the cancer cells can’t stop the cell cycle, accumulate errors and this leads to cell death
  • Normal cells will be able to stop the cell cycle
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are common resistance mechanisms to alkylating agents?

A
  1. Inc. DNA repair (Inc. expression of guanine 06 alkyl transferase)
  2. Inc. glutathione production (trapping agent)
  3. Oral = Dec. activation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How is cyclophosphamide activated?

A
  • Derivative of mechlorethamine that must be activated by LIVER CYP450 enzymes as the first step in a multistep activation process
  • Induction/inhibition of CYP2B6 by other drugs will have the opposite effect on CYCLOPHOSPHAMIDE than conventional drug/drug interactions (induction of the enzyme increases activity)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How is mechlorethamine activated?

A

Immediate activation upon H2O exposure!!

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

What are the most common cross linking agents used?

A
  • Cyclophosphamide
  • Cisplatin
  • Subtyping cancer to identify the best drug is common!
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are common toxicities of cross linking agents?

A
  1. Cytotoxic side effects
    - Particularly strong nausea & vomiting - esp. Mechlorethamine & Cisplatin!
  2. Vesicant – will cause blistering (Dec. oral agents)
  3. Mutagenic, Carcinogenic (AML especially), Teratogenic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What cross linking agents are taken orally?

A
  • Cyclophosphamide, Ifosfamide
  • Busulfan
  • Melphalan
  • Chlorambucil
26
Q

What cross linking drug methylates DNA?

A

Temozolomide (TMZ)

27
Q

What cross linking drugs are lipid soluble (cross BBB)?

A

Temozolomide (TMZ), Nitrosoureas (Carmustine, Lomustine)

28
Q

What cross linking agent causes a tan appearance?

A

Busulfan-tan!

29
Q

What cross linking agent causes nausea (emetic), oto and renal toxicity?

A

Cisplatin, Carboplatin, oxaloplatin

30
Q

What cross linking drug causes hemorrhagic cystitis?

A

Cyclophosphamide, Ifosfamide

31
Q

What crossing linking drug is a vesicant and emetic?

A

nausea & burning (must be IV)

-Mechlorethamine

32
Q

What are the intercalating agents?

A

Anthracycline Antibiotics: Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Mitoxantone

33
Q

What are antrhacycline antibiotics important in treating?

A

Breast cancer!!

34
Q

When is doxorubicin most toxic?

A

Its CCNS but its most toxic during S phase!

35
Q

How does resistance develop to antracycline antibiotics?

A
  1. Inc. accumulation due to Inc. P-glycoprotein expression
  2. Dec. Topo II activity (temporarily)
  3. Inc. inactivation
36
Q

What is the pharmacokinetics of intercalating agents?

A
  • Given IV (vesicant)

- Metabolized in the liver –> excreted in the bile!

37
Q

What is the most commonly used antineoplastic?

A

DOXORUBICIN!! = Adriamycin

-Athracycline antibiotics = 1st line treatment for breast cancer

38
Q

What toxicity is associated with intercalating agents?

A
  1. Cytotoxic (bone marrow suppression)
  2. Unusual cardiomyopathy (causes you to stop a drug & start a different one)
  3. Damage DNA
  4. Radiation Recall Reaction
  5. Red urine (not blood though)
39
Q

What is the reason you stop and give a break in intercalating agents?

A

Bone marrow suppression (cytotoxic)

-You stop and let normal cells recover for a bit and then you restart!

40
Q

What causes the unusual cardiomyopathy?

A
  • Often irreversible
  • Related to total dose in lifetime
  • Acute: Inc. HR, arrhythmia
  • Delayed: CHF (congestive heart failure) years after treatment stopped - unresponsive to standard treatment (digitalis)
41
Q

What does mitoxantone cause?

A

-Blue urine, turns fingernails & sclera of the eyes blue

42
Q

What is “radiation recall reaction”?

A

Erythema and desquamation of the skin at sites of prior radiation therapy

43
Q

What do all drugs that cause strand breaks and prevent DNA replication have in common?

A

-All are CCS - work in G2/M

44
Q

What antibiotic causes strand breaks and/or prevents DNA Replication?

A

Bleomycin

45
Q

What plant alkaloids cause strand breaks and/or prevent DNA Replication?

A
  • Etoposide (epipodophyllotoxin)
  • Irinotecan
  • Topotecan (camptothecins)
46
Q

What are the misc drugs that cause strand breaks and/or prevent DNA Replication?

A

Procarbazine (alkylating agent!)

47
Q

What does bleomycin do to DNA?

A

BLEOMYCIN BLASTS!

  1. Binds to DNA
  2. Generates free radicals
  3. Cuts DNA into pieces
  4. Cells accumulate in G2 and die
48
Q

What do the MOA for drugs that cause strand breaks and/or prevent DNA replication require?

A

Apoptic machinery –> i.e. where p53 is NOT mutated

49
Q

What does Etoposide target?

A

It’s a Topoisomerase II inhibitor (more effective drug!)

  • -More specific for rapidly dividing cells
  • -Harder to repair
50
Q

What does Irinotecan and Topotecan target?

A

It’s a Topoisomerase I inhibitor

51
Q

What are the -TECANS (IRINO and TOPO) metabolized?

A

In the liver. They are also activated here!!

52
Q

What is the mechanisms of Procarbazine?

A

Alkylating

-More effects on RNA & protein synthesis than others and more strand breaks

53
Q

How is resistance developed against Bleomycin?

A
  1. Inc. DNA repair

2. Inc. Inactivation (HYDROLASE - skin & lungs –> side effects)

54
Q

How has resistance developed against Etoposide?

A
  1. Inc. P-glycoprotein => MDR

2. Dec. activation

55
Q

How has resistance developed against Irinotecan/Topotecan?

A
  1. Inc. P-glycoprotein => MDR

2. Dec. activation

56
Q

What is Bleomycin’s therapeutic use?

A

-In combination (unique mechanism of action)

57
Q

What is Irinotecan/Topotecan’s therapeutic use/

A

Metastatic colon cancer

58
Q

What’s unique about the toxicity of drugs that cause strand breaks and/or prevent DNA replication?

A

(topoisomerase inhibitors)

-Less cytotoxic side effects!

59
Q

What toxicity develops with Bleomycin?

A
  1. Skin & lung damage (no hydrolase)
  2. Hypersensitivity reactions
  3. Edema
60
Q

What toxicity develops with Etoposide?

A

Cardiovascular - CV (hypotension)

61
Q

What toxicity develops with Irinotecan/Topotecan?

A
  1. Excreted in the Bile
    —> causes severe diarrhea
    A) Acute phase: cholinergic –> treat with atropine
    B) Late phase: dehydration, electrolyte imbalances => opiates (Loperamide)

IHO Block 3 (13 decks)

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