Principles 1-4 Flashcards
what are chemotherapeutic agents
chemical compounds used to treat disease
what do antimicrobials do
destroy pathogenic microbes or inhibit their growth within the host
what do antibiotics do
destroy or inhibit bacteria
most antibiotics are ____ or_____
microbial products; their derivatives
what antibiotics are used to treat streptomyces spp
-amphotericin B
- chloramphenicol
-erythromycin
-kanamycin
-neomycin
-nystatin
-rifampin
-streptomycin
-tetracylcines
- vancomycin
what antibiotic is used to treat micromonospora spp
gentamicin
what antibiotics are used to treat bacillus spp
bacitracin and polymyxins
what antibiotics are used to treat penicillium spp
- griseofulvin and penicillin
what antibiotics are used to treat cephalosporium spp
cephalosporins
what is selective toxicity
ability of drug to kill or inhibit pathogen while damaging host as little as possible
what is a therapeutic dose
drug level required for clinical treatment
what is a toxic dose
drug level at which drug becomes too toxic for patient
what is the therapeutic index
ratio of toxic dose to therapeutic dose
what do bacteriocidal antibiotics do
kill bacteria
what do bacteriostatic antibiotics do
inhibit growth of bacteria
what do broad spectrum antibiotics do
attack many different bacteria, gram positive and gram negative
what do narrow spectrum antibiotics do
attack only a few different bacteria
what is MIC ( minimal inhibitory concentration)
lowest concentration of drug that inhibits growth of pathogen
what is MBC (minimal bacteriocidal concentration)
lowest concentration of drug that kills pathogen
what are the two techniques that are normally used to determine MIC and MBC
-dilution susceptibility tests
- disk diffusion tests
describe dilution susceptibility tests
-involves inoculating media containing different concentrations of drug
- broth or agar with lowest concentration showing no growth is MIC
-tubes showing no growth can be subcultured into drug free medium and broth from which microbe cannot be recoverred is MBC
what are dilution suscpetibility tests useful for
determining which drug would be best for the patient
describe disk diffusion tests
- disks impregnanted with specific drugs are placed on agar plates inoculated with test microbe
- drug diffuses from disk into agar, establishing concentration gradient
- observe clear zones of no growth around disks
what is the kirby bauer method
standardized method for carrying out disk diffusion test
- sensitivity and resistance determined using tables that relate zone diameter to degree of microbial resistance
- values are plotted and used to determine if concentration of drug reached in body will be effective
what concentrations of a drug at infection site is needed to be effective
a concentration greater than MIC
what can be used to determine concentration of drug in blood
microbiological, chemical, immunological, enzymatic or chromatographic assays
what are the factors influencing the effectiveness of antimicrobial drugs
- ability of drug to reach site of infection
-ability of drug to reach concentrations in body that exceed MIC of pathogen - susceptibility of pathogen to drug
what does the ability of the drug to reach the site of infection depend on
- mode of transmission: oral, topical, parenteral routes
- drug can be excluded by blood clots or necrotic tissue
what are parenteral routes
nonoral routes of administration
what are some factors infleucning ability of drug to reach concentrations exceeding MIC
- amount administered
-route of administration
-speed of uptake
-rate of clearance from body
does a drug required bacterial cell growth to be effective
some drugs do
what does the susceptibility of pathogen to drug depend on
- speed of action of a drug
- if drug requires bacterial cell growth
what are the mechanism of action of antimicrobial agents
- disruption of bacterial cell wall
- inhibition of protein synthesis
- inhibition of nucleic acid synthesis
what are the the categories of antimicrobial agents and the specific drugs that disrupt bacterial cell wall
- Beta-lactams: penicillins, cephalosporins, carbapenems and monobactams and beta lactamase inhibitors
- glycopeptides: vancomycin and teichoplanin
- polypeptides: bacitracin and polymixins
-others: cycloserine, isoniazid and ethionamide, ethambutol
what is peptidoglycan made of
alternating NAM and NAG sugars
which type of bacteria has a much larger peptidoglycan layer
gram positive
describe peptidoglycan synethesis
-peptidoglycan repeat unit forms in cytoplasm, involved use of uridine diphosphate (UDP) as a carrier
- repeat unit then transported across membrane by bactoprenol
- repeat unit attached to growing peptidoglycan chain
-cross links formed by transpeptidation
what is the molecule involved in cross linkage in peptidoglycans in gram negatives
DAP and D-ala
what type of bacteria is E coli
gram negative
what type of bacteria is staphylococcus aureus
gram positive
what molecule cross links peptidoglycans in gram positive bacteria
D- ala and L-Lys by a peptide interbridge
what is transpeptidation
the exchange of one peptide bond for another
what do Beta lactam antibiotics do
inhibit transpeptidation
what does penicillin G act on and what is it destroyed by
high activity against most gram positive bacteria, low against gram negative, destroyed by acid and penicillinase
what does ampicillin act on
active against gram positive and gram negative bacteria, acid stable
what is methicillin resistant to and is it affected by acid
penicillinase, but less active than penicillin G, acid labile
what are beta lactamase inhibitors
not antibiotics but they help beta lactam antibiotics by preventing their degradation by beta lactamases
what are beta lactamases
enzymes produced by some bacteria that are resistance to beta lactam antibiotics
what are examples of beta lactamase inhibitors
clavulanic acid, sulbactam and tazobactam
what was the first combination of beta lactam antibiotic and beta lactamase inhibitor and what was it made of
-augmentin
- amoxicillin and clavulanic acid
what does vancomycin do
-binds terminal D- Ala-D-Ala and sterically inhibits addition of peptidoglycan subunits to the cell wall
- binds to existing peptidoglycan chains and inhibits the transpeptidation reaction that crosslinks the chains
what infections do vancomycin and teicoplanin treat
antibiotic resistance staphylococcal and enterococcal infections
what do bacitracins do
prevent recycling of lipid carrier
what do polymixins do
binds phospholipids and disrupts outer and inner membranes of gram negative bacteria
why are many polymixins topical
its a more general mode of action because they are toxic
what is cycloserine used for
second line of treatment for mycobacterium tuberculosis
what is special about cycloserine
- it is a cyclic analog of alanine
- crosses blood brain barrier and is an NMDA receptor agonist
what do isoniazid and ethionamide do
inhibits mycobacteria by affecting synthesis of mycolic acid
what is mycolic acid
an abundant wax in the cell wall
what does ethambutol do
inhibits mycobacteria by affecting attachment of mycolic acid in the cell wall
describe how proteins are synthesized in ribosomes
- start with free ribosomes and mRNA
- 30S ribosomal subunit is formed and joined with a charged tRNA molecule
- initiation factors form the 30S initiation complex
- initiation factors add a 50S ribosomal subunit to make the 70S initiation complex where the tRNA is in the P site
- a peptidyltransferase reaction occurs where the amino acid from the A site is added to the growing chain off the tRNA in the P site
- a translocation reaction occurs where a tRNA in the A site is moved to the P site
what makes up the 30S ribosomal subunit
16S rRNA and about 20 proteins
what makes up the 50S ribosomal subunit
23S and 5S rRNA and about 30 proteins
what drug falls under the category of oxazolidinones and what does it do
- linezolid
- binds 23S rRNA and prevents formation of 70S initiation complex
- inhibition of protein synthesis
what do tetracyclines do
- bind 16S rRNA of 30S subunit and prevent binding of aa-tRNA to A site
- inhibition of protein synthesis
what drugs fall under the category of aminoglycosides and what do they do
- streptyomycin
-amikacin - gentamycin
- tobramycin
- bind to 30S subunit and distort A site, causing translation misreading which inhibits protein syntheiss
what do chloramphenicol and lincosamides do
bind to 50S subunit and inhibit peptidyltransferase activity
-inhibition of protein synthesis
what drugs fall under the category of macrolides and what do they do
- erythromycin, azithromycin, clarithromycin
- binds 23S rRNA in the 50S subunit and block the translocation reaction
- also prevent further formation of the 50S subunit
- inhibition of protein synthesis
what drugs fall under the category of quinolones and what do they do
-ciprofloxacin and other -floxacins
- interfere with type II topoisomerases such as DNA gyrase or topoisomerase IV and stabilizes DNA double strand breaks
- inhibition of nucleic acid synthesis
what do rifampin and rifabutin do
bind to RNA polymerase and prevent the initiation of transcription
what does metronidazole do
- a prodrug with no inherent antimicrobial activity
- produces DNA damaging radicals under anaerobic conditions via enzymes functioning in anaerobes and microaerophiles
- inhibition of nucleic acid synthesis
what are drugs that fall under the class of antimetabolites and what do they do
-sulfonamides, trimethoprim, dapsone, and p-aminosalicyclic acid
- prevents formation of precursors of folic acid
do humans make folic acid? do bacteria?
humans dont bacteria do
drug resistance can often be transmitted to_____
other bacteria
what are the resistance mechanisms of bacteria to antibiotics
- impermeable barrier
- target modifications
-antibiotic modification - efflux pump mechanism
how does the impermeable barrier confer drug resistance
the bacterial cell membrane develops an impermeable barrier which blocks antibiotics
how does target modification confer drug resistance
modification of components of the bacteria which are targeted by the antibiotic, meaning the antibiotic can no longer bind properly to its target in order to destroy the bacteria
how does antibiotic modification confer drug resistance
the cell produces substances (usually an enzyme) that inactivate the antibiotic before it can harm the bacteria
how does the efflux pump mechanism confer drug resistance
antibiotic is actively pumped out of the bacteria so that it cannot harm the bacteria
are penicillins and cephalosporins plasmidborne and what is their resistance mechanism to antibacterial agents
- yes
- hydrolysis of beta lactam ring by beta lactamase
is methicillin plasmidborne and what is its resistance mechanism to antibacterial agents
- no
- change in penicillin binding protein
are tetracycline plasmidborne and what is its resistance mechanism to antibacterial agents
- yes
- efflux pump pushed drug out of cell
are oxazolidinones plasmidborne and what is its resistance mechanism to antibacterial agents
-no
- mutation in 23S rRNA
are quinolones plasmidborne and what is its resistance mechanism to antibacterial agents
- no
- mutations in genes encoding DNA gyrase and topoisomerase IV
what is the origin and transmission of drug resistance
- new mutations of bacterial genes that encode the targets of antibiotics
- pre-existing resistance genes that are transmitted from one bacterium to another
what are the genetic elements involved in resistance gene spreading (dissemination)
- plasmids
- transducing bacteriophage
- bacterial chromosomal genes
- transposons
- integrons
how do plasmids transfer
conjugation
how do transducing bacteriophages transfer and how
transduction by packaging non-phage DNA
how do bacterial chromosomal genes transfer and how
transformation by mutations
how are transposons involved in resistance gene dissemination
hop into other genetic elements
what are integrons and where are they found
- segments of DNA containing complete sets of genes
- found of plasmids, transposons, and bacterial chromosomes
what is superinfection and what causes it
development and spread of drug resistant pathogens caused by drug treatment which destroys drug sensitive strains
what does the killing of normal flora result in
uninhibited growth of potentially pathogenic bacteria and fungi
what does normal flora produce
antibacterial substances and competes with pathogenic bacteria for essential nutrients
what are the common organisms in superinfections
- clostridium difficile
- MDR (multi drug resistant) gram negative rods
- MRSA (methicillin resistant staphylococcus aureus
- candida or other fungi
what is clostridium difficile
spore forming agent of pseudomembranous colitis
how can you prevent emergence of drug resistance
- give drug in high concentrations
-give two or more drugs at the same time - use drugs only when necessary
what organisms are antibiotic resistant public health threats
- clostridium difficile
- carbapenem resistant enterobacteriaceae
- neisseria gonorrhoeae
-fluconazole resistant candida
