L4 Flashcards
Requirement of a good antimicrobial?
Antimicrobials must act within the host without damaging the host (selective toxicity; “magic bullet”)
What organism do antibiotics target
Bacteria
Why are eukaryote pathogens more difficult to target for antimicrobials?
Eukaryote pathogens have cells more like our own so more difficult to treat cause not as much difference btwn pathogen cells and your cells.
Describe the five main mechanisms of action of antibiotics on bacterial cells. Provide an example of each drug that uses each mechanism. Draw a diagram of a bacteria cell and indicate where each mechanism acts.
Slide 4
- Inhibition of CELL WALL SYNTHESIS:
- All bacteria have a cell wall, while human hosts do not. Its primary component is peptidoglycan.
- E.g. Vancomycin - Inhibition of PROTEIN SYNTHESIS:
E.g. Erythromycin - Inhibition of NUCLEIC ACID REPLICATION and TRANSCRIPTION:
E.g. Rifampin - Injury to PLASMA MEMBRANE:
- E.g. Polymyxin B - Inhibition of essential METABOLITE SYNTHESIS:
- E.g. Trimethoprim
What are the 3 ways antibiotics can block protein inhibition? Give an example of an antibiotic for each case.
- Change shape of 30S portion, causing code on mRNA to be read incorrectly
- E.g. Streptomycin - Bind to 50S portion and inhibits formation of peptide bond (sit near or in active site)
- E.g. Chloramphenicol - Interfere with attachment of tRNA to mRNA-ribosome complex
- E.g. Tetracyclines
How does chemotherapy work
Using a compound that selectively targets and destroy abnormal or pathogenic cells (or viruses)
What is an antiviral
Target different steps in viral replication
What steps can an anti-viral target?
- Inhibitors of fusion/entry of the virus to target host cell (e.g. block receptors on host cell that virus binds to)
- Inhibit uncoating
- Inhibit integration
- Inhibit nucleic acid synthesis
- Protease inhibitors
- Exit/release inhibitors
How do NUCLEOSIDE ANALOGS (Base + sugar) inhibit synthesis of viral DNA or RNA? Provide an example of one.
- Nucleoside analogs can shut down replication of viral DNA
- In HSV infected cells, acyclovir impairs synthesis of viral DNA when it is incorporated into the 5’-3’ growing strand by DNA polymerase. Normally thymidine kinase phosphorylates nucleosides to form nucleotides to be incorporated into DNA by pol. In a healthy cell, TK recognizes non-nucleosides e.g. acyclovir, and will not phosphorylate them and will “ignore” acyclovir. But in virally infected cells, TK is altered and doesn’t recognize acyclovir as a non-nucleoside, which will then be phosphorylated and incorporated into growing strand of DNA. Acyclovir structurally resembles the nucleoside deoxyguanosine, but missing 3’OH. As it’s missing the 3’OH, no longer able to add another nucleotide and DNA synthesis is halted
What is HAART?
- Highly active antiviral therapy
- Use combinations of drugs to minimize survival of resistant strains
- Usually 2 RT inhibitors and either a protease or integrase inhibitor in combo
What are the 2 types of reverse transcriptase inhibitors? Give an example of each.
- Nucleoside reverse transcriptase inhibitor (NRTIs)
- Inhibits reverse transcriptase, preventing transcription of viral RNA into DNA
- E.g. tenofovir - Non-nucleoside reverse transcriptase inhibitor (NNRTs)
- Inhibits reverse transcriptase, preventing transcription of viral RNA into DNA
- E.g. Efavirenz
Fxn of integrase inhibitors? Example
- Inhibit HIV integrase that integrates cDNA into the host chromosome
- E.g. Raltegravir
Fxn of protease inhibitors? Example
- Inhibit proteases that cleave viral precursor proteins into structural and functional proteins
- E.g. Indinavir
Fxn of maturation inhibitors?
interfering with the maturation of the virus e.g. bind gag protein and disrupts its processing
Fxn of tetherins?
Tether viruses to the cells, preventing their release and spread
