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Chemotherapy Flashcards

1
Q

Why do microbes require a cell wall?

A

Prevents unlimited swelling that would occur due to high osmotic pressure

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2
Q

List 5 features of prokaryotes distinct from eukaryotes that represent exploitable differences

A 
Cell wall
Nucleic acid synthesis 
Protein synthesis 
The cell membrane
Respiratory election transport chain
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3
Q

What are bacteriocidal antibiotics?

A

Kill bacteria

Do not require a competent immune system

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4
Q

Describe gram negative bacteria.

A

Doesn’t stain with violet gram stain
Thin wall
Complex lipopolysaccharide/proteoglycan wall
More resistant to antibiotics due to compex wall

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5
Q

What is the mycobacteria cell wall features?

A

Composed of mycolic acid

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6
Q

What are bacteriostatic drugs?

A

Slow bacterial proliferation
Reduced the ability for microbes to divide
Require a competent immune system to work

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7
Q

What is the fungi cell wall features?

A

Uses ergosterol instead of cholesterol as primary sterol

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8
Q

What are the glycopeptide components of the proteoglycan cell wall

A

N-acetyl-glucosamide

N-acetyl-muramate

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9
Q

What is the enzyme responsible for cross-linking the polymers?

A

Transpeptidase

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10
Q

What specific amino acid dipeptide is bound and cleaved by transpeptidase?

A

D-analyl-D-alanine

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11
Q

Why won’t beta-lactam antibiotics affect human alanine cross links?

A

Human alanine is L-alanine
Human transpeptidase will not recognise and bind to beta-lactams as the receptor site will be stereospecific for L-alanine.

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12
Q

What are the beta-lactams?

A

Penicillins
Cephalosporins
Carbepanems

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13
Q

What does the beta-lactam ring mimic? What is its affect?

A

Mimic the D-alanyl-D-alanine peptide bonds

It’s inhibits transpeptidase

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14
Q

How do the beta-lactamase enzymes eliminate the effectiveness of the beta lactams?

A

It hydrolysises the amide bond of the beta lactam ring. This causes ring opening, deactivating the antibiotic

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15
Q

What limited the bioavailability of penicillin? How was this addressed?

A

Beta-lactamases eliminated the effectives of penicillin

Semi-synthetic penicillins resistant to beta-lactamases were produced

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16
Q

What improvements have been made to penicillins?

A

Gastric acid resistance

Wider range/specificity to different strains

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17
Q

With a beta-lactamase sensitive penicillin, what adjuncts can be used to increase bioavailability?

A

Clavulanic acid

Inhibits beta-lactamase

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18
Q

If infected with MRSA, what antibiotic is used? What’s the mechanism?

A

Vancomycin:

Inhibits proteoglycan wall synthesis by high affinity binding to precursors preventing transglycosylation

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19
Q

Describe gram positive bacteria

A

Stain with violet gram stain
Thick wall
Simple peptidoglycan wall

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20
Q

What do polymixins do?

A

Interact with phospholipids (loosening the wall) of the cell wall, destroying the selective barrier function, so the bacteria is flooded with unwanted ions

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21
Q

Name a penicillin resistant to beta-lactamase activity

A

Flucloxacillin

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22
Q

Are polymixins more effective against gram negative or positive bacteria?

A

Gram negative

They’re selective for lipopolysaccharides

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23
Q

Why are polymixins limited to topical use?

A

They’re not absorbed by the GI tract

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24
Q

List antibiotics used to treat tuberculosis and leprosy

A

Isoniazid

Ethambutol

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25
What part of the folic acid molecule do sulphonamides mimic?
The pABA region
26
What mimics the pteridine part of the folic acid molecule?
Trimethoprim
27
What do sulphonamides do?
Inhibit dihydropteroate synthase, preventing the conversion of pABA to folate
28
What does trimethoprim do?
Inhibits dihydrofolate reductase preventing the conversion of folate to tetrahydrofolate
29
Which sulfonamide derivative has activity against mycobacteria?
Sulfones
30
What do quinolones do?
Bacteriocidal | They inhibit DNA topoisomerase II
31
What does rifamycin do?
They're macrocyclic antibiotics Targets mycobacteria causing leprosy and tuberculosis Inhibits DNA polymerase
32
What's the difference between eukaryotic and prokaryotic ribosome structures?
Eukaryotic are denser, having 40S and 60S subunits Prokaryotic ribosomes have 30S and 50S
33
What do tetracyclines do?
Affect aminoacyl tRNA binding
34
What do aminoglycosides do?
They affect the recognition of aminoacyl tRNA/mRNA to codon/anticodon
35
What antibiotic affects transpeptidation in protein synthesis?
Chloramphenicol
36
What causes peptidyltranslocation?
Macrolides
37
How do 5-nitroimadazoles operate to eliminate anaerobic bacteria?
If oxygen is not terminal acceptor, the electron transport chain (ETC) is at a lower potential They're terminal acceptors at a sufficiently low potential Ferrodoxin in the ETC transports 2 electrons to 5-nitroimadazoles Reduction converts drug to a cross linker which disrupts DNA integrity ETC in humans at a potential too high
38
What drug inhibits ergosterol synthesis
Imadazole/triazole
39
What drug permeates fungal membrane by interacting with ergosterol?
Polyene
40
What drug inhibits fungal mitosis?
Griseofulvin: | Binds to tibulin, interfering with microtubule function
41
Give the 4 exploitable stages of the viral life cycle
Attachment and entry Viral nucleic acid replication Production of viral proteins, coat assembly of virions Viral relaease, shedding and egress
42
How can you target viral entry?
Interfering with how they interact with host cell receptors | Pinocytosis
43
Whats a positive virus?
Their genes can be directly accessed by host ribosomes
44
What's a negative virus?
Genes cannot be directly accessed by host ribosomes
45
What's a retrovirus?
Virus has RNA which is coverts to DNA which is then processed
46
What are the 4 types of virus?
Positive Negative Retro DNA
47
What drug actually like amantadine?
Rimantidine
48
How does amantadine work?
Binds to viral coded H channel (M2) to prevent endosome acidification Since pH is not low enough, the viral membrane cannot fuse with the endosome membrane The virus cannot enter the cell
49
What is the more accurate name of reverse transcriptase?
RNA dependent DNA polymerase
50
Why are nucleoside rather than nucleotide analogues used as drugs?
Nucleosides can cross the cell membrane | Nucleotides are too charged
51
Name 2 nucleoside inhibitors of reverse transcriptase used for HIV.
AZT ddC
52
What feature of nucleoside inhibitors suppress viral nucleic acid synthesis?
DNA chain termination
53
Name a non-nucleoside reverse transcriptase inhibitor
C1-TIBO
54
Name a HIV protease inhibitor
Indinavir
55
Why do protease inhibitors represent an exploitable difference?
Viral proteins are polycistronic They require a viral protease to cleave the propeptide into structural proteins Inhibiting the viral protease prevents the formation of the structural proteins
56
What is HAART?
High activity antiretroviral therapy Decreases the mutation probability conferring mutatation NRTIs, NNRTIs, protease inhibitors are used in combo. And sub. max. doses to reduce toxicity
57
Name a drug that selectively affects infected cells. How does it work?
Aciclovir: | Selectively phosphorylated by viral thymidine kinase
58
What does foscarnet do?
Treats cytomegalovirus
59
What's the mechanism of action of ribavarin?
Inhibits RNA polymerase | Inhibits GTP dependent enzymes (affects viral mRNA capping)
60
What are endogenous antiviral agents?
Interferons
61
What do interferons do?
Inhibit the entry of viruses Induce latent RNAase (degrades viral mRNA) Suspension of ribosome function by phosphorylation and inhibition of eIF2
62
Name 2 neuraminidase inhibitors
Osaltamivir | Zanamivir
63
How does enfurviratide work?
Causes the fusion of HIV I a macrophage membrane and then entry into the macrophage
64
Name the four main classes of anti cancer drugs
Alkylating agents Antimetabolites Cytotoxic antibodies Plant derivatives
65
How do nitrogen mustards, nitrosureas, and cisplatins operate to inhibit cell proliferation?
Cross link guanine nucleotides in DNA so DNA cannot be replicated or transcribed
66
What stage of cell cycle donitrogen mustards, nitrosureas, and cisplatins target?
S phase
67
Describe a cytotoxic antibody
Doxorubicin: | Inhibits the synthesis of nucleic acids in cancer therapy
68
Describe a plant alkaloid
Etoposide: | Inhibits the synthesis of nucleic acids in cancer therapy
69
Describe an antimetabolite.
Melbotrexate: | Inhibits the synthesis of nucleic acids in cancer therapy
70
Name 3 cytotoxic drugs that inhibit polymerase activity
Dactinomycin Doxorubicin Etoposide
71
What cell phase do vinca alkaloids and toxanes target?
M Phase
72
What anti cancers prevent microtubule polymerisation, hence mitosis?
Vinca alkaloids and toxanes

Med Chem modules (8 decks)

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