Chemotherapy Flashcards
Why do microbes require a cell wall?
Prevents unlimited swelling that would occur due to high osmotic pressure
List 5 features of prokaryotes distinct from eukaryotes that represent exploitable differences
Cell wall Nucleic acid synthesis Protein synthesis The cell membrane Respiratory election transport chain
What are bacteriocidal antibiotics?
Kill bacteria
Do not require a competent immune system
Describe gram negative bacteria.
Doesn’t stain with violet gram stain
Thin wall
Complex lipopolysaccharide/proteoglycan wall
More resistant to antibiotics due to compex wall
What is the mycobacteria cell wall features?
Composed of mycolic acid
What are bacteriostatic drugs?
Slow bacterial proliferation
Reduced the ability for microbes to divide
Require a competent immune system to work
What is the fungi cell wall features?
Uses ergosterol instead of cholesterol as primary sterol
What are the glycopeptide components of the proteoglycan cell wall
N-acetyl-glucosamide
N-acetyl-muramate
What is the enzyme responsible for cross-linking the polymers?
Transpeptidase
What specific amino acid dipeptide is bound and cleaved by transpeptidase?
D-analyl-D-alanine
Why won’t beta-lactam antibiotics affect human alanine cross links?
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.
What are the beta-lactams?
Penicillins
Cephalosporins
Carbepanems
What does the beta-lactam ring mimic? What is its affect?
Mimic the D-alanyl-D-alanine peptide bonds
It’s inhibits transpeptidase
How do the beta-lactamase enzymes eliminate the effectiveness of the beta lactams?
It hydrolysises the amide bond of the beta lactam ring. This causes ring opening, deactivating the antibiotic
What limited the bioavailability of penicillin? How was this addressed?
Beta-lactamases eliminated the effectives of penicillin
Semi-synthetic penicillins resistant to beta-lactamases were produced
What improvements have been made to penicillins?
Gastric acid resistance
Wider range/specificity to different strains
With a beta-lactamase sensitive penicillin, what adjuncts can be used to increase bioavailability?
Clavulanic acid
Inhibits beta-lactamase
If infected with MRSA, what antibiotic is used? What’s the mechanism?
Vancomycin:
Inhibits proteoglycan wall synthesis by high affinity binding to precursors preventing transglycosylation
Describe gram positive bacteria
Stain with violet gram stain
Thick wall
Simple peptidoglycan wall
What do polymixins do?
Interact with phospholipids (loosening the wall) of the cell wall, destroying the selective barrier function, so the bacteria is flooded with unwanted ions
Name a penicillin resistant to beta-lactamase activity
Flucloxacillin
Are polymixins more effective against gram negative or positive bacteria?
Gram negative
They’re selective for lipopolysaccharides
Why are polymixins limited to topical use?
They’re not absorbed by the GI tract
List antibiotics used to treat tuberculosis and leprosy
Isoniazid
Ethambutol
What part of the folic acid molecule do sulphonamides mimic?
The pABA region
What mimics the pteridine part of the folic acid molecule?
Trimethoprim
What do sulphonamides do?
Inhibit dihydropteroate synthase, preventing the conversion of pABA to folate
What does trimethoprim do?
Inhibits dihydrofolate reductase preventing the conversion of folate to tetrahydrofolate
Which sulfonamide derivative has activity against mycobacteria?
Sulfones
What do quinolones do?
Bacteriocidal
They inhibit DNA topoisomerase II
What does rifamycin do?
They’re macrocyclic antibiotics
Targets mycobacteria causing leprosy and tuberculosis
Inhibits DNA polymerase
What’s the difference between eukaryotic and prokaryotic ribosome structures?
Eukaryotic are denser, having 40S and 60S subunits
Prokaryotic ribosomes have 30S and 50S
What do tetracyclines do?
Affect aminoacyl tRNA binding
What do aminoglycosides do?
They affect the recognition of aminoacyl tRNA/mRNA to codon/anticodon
What antibiotic affects transpeptidation in protein synthesis?
Chloramphenicol
What causes peptidyltranslocation?
Macrolides
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
What drug inhibits ergosterol synthesis
Imadazole/triazole
What drug permeates fungal membrane by interacting with ergosterol?
Polyene
What drug inhibits fungal mitosis?
Griseofulvin:
Binds to tibulin, interfering with microtubule function
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
How can you target viral entry?
Interfering with how they interact with host cell receptors
Pinocytosis
Whats a positive virus?
Their genes can be directly accessed by host ribosomes
What’s a negative virus?
Genes cannot be directly accessed by host ribosomes
What’s a retrovirus?
Virus has RNA which is coverts to DNA which is then processed
What are the 4 types of virus?
Positive
Negative
Retro
DNA
What drug actually like amantadine?
Rimantidine
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
What is the more accurate name of reverse transcriptase?
RNA dependent DNA polymerase
Why are nucleoside rather than nucleotide analogues used as drugs?
Nucleosides can cross the cell membrane
Nucleotides are too charged
Name 2 nucleoside inhibitors of reverse transcriptase used for HIV.
AZT ddC
What feature of nucleoside inhibitors suppress viral nucleic acid synthesis?
DNA chain termination
Name a non-nucleoside reverse transcriptase inhibitor
C1-TIBO
Name a HIV protease inhibitor
Indinavir
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
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
Name a drug that selectively affects infected cells. How does it work?
Aciclovir:
Selectively phosphorylated by viral thymidine kinase
What does foscarnet do?
Treats cytomegalovirus
What’s the mechanism of action of ribavarin?
Inhibits RNA polymerase
Inhibits GTP dependent enzymes (affects viral mRNA capping)
What are endogenous antiviral agents?
Interferons
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
Name 2 neuraminidase inhibitors
Osaltamivir
Zanamivir
How does enfurviratide work?
Causes the fusion of HIV I a macrophage membrane and then entry into the macrophage
Name the four main classes of anti cancer drugs
Alkylating agents
Antimetabolites
Cytotoxic antibodies
Plant derivatives
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
What stage of cell cycle donitrogen mustards, nitrosureas, and cisplatins target?
S phase
Describe a cytotoxic antibody
Doxorubicin:
Inhibits the synthesis of nucleic acids in cancer therapy
Describe a plant alkaloid
Etoposide:
Inhibits the synthesis of nucleic acids in cancer therapy
Describe an antimetabolite.
Melbotrexate:
Inhibits the synthesis of nucleic acids in cancer therapy
Name 3 cytotoxic drugs that inhibit polymerase activity
Dactinomycin
Doxorubicin
Etoposide
What cell phase do vinca alkaloids and toxanes target?
M Phase
What anti cancers prevent microtubule polymerisation, hence mitosis?
Vinca alkaloids and toxanes
