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Who proposed the use of chemicals as "magic bullets" and how would they work?
- Paul Ehrlich
- bound to receptor pathogens and ignored the host
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What was Alexander Flemings contribution?
he found a mold (Peniclillium notatum) in 1928 that had antibacterial action
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What was the first practical antimicrobial drug, and when was it discovered?
- sulfanilimide
- Gerhard Domagk
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Who coined the term "antibiotics" and discovered antimicrobials from streptomyces?
Selman Waksman
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Difference between antibiotics, semisynthetics and synthetics
- antibiotics: meaning antimicrobials produced by an organism
- semisynthetics: chemically altered antibiotics
- synthetics: chemicals completely made in the lab
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What is "selective toxicity"?
toxic to pathogen, but no to host
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Compare prokaryotes, eukaryotes, and viruses in terms of how they may affect selective toxicity of drugs
- prokaryotes: easier because there are many differences , so we have lots of drugs what work against bacteria
- eukaryotes: harder
- virues: really hard since they utilize the host's enzymes and ribosomes to metabolize and replicate
- cant use antibiotics on viruses
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drug that affects the cell walls of bacteria and fungi
Beta-lactams: natural penicillins and cephalosporins, semisynthetic penicillins- what advantage of the semisynthetics?
- mos effective against G+ organisms
- semisynthetics are more stable in acid environments, more readily absorbed, less susceptible to bacterial enzymes
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drug that affects the cell walls of bacteria and fungi
vancomycin?
streptomyces orientalis
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drug that affects the cell walls of bacteria and fungi
Bactracin?
drugs have no effect on dormant bacteria- cells must be growing for effect to take place
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drug that affects the cell walls of bacteria and fungi
Isoniazid?
- used to treat TB
- attack mycolic acids in cell wall of Mycobacterium tuberculosis
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drug that affects the cell walls of bacteria and fungi
Echinocandins (caspofungin)
- fungal cell walls
- inhibit glucan synthesis, the components of fungal cell walls
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drugs that inhibit protein synthesis
Aminoglycosides?
change the shape of the ribosome
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drugs that inhibit protein synthesis
Tetracyclines?
block tRNA docking
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drugs that inhibit protein synthesis
Chloramphenical, erythromycin
inhibit the ribosomes
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drugs that inhibit protein synthesis
Antisense nucleic acids
- RNA or single-stranded DNA molecules
- complementary to specific RNA molecules in prokaryotes only
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drugs that disrupt the cytoplasmic membrane
Polyenes? nystatin, amphotericin B
- anitifungal
- do the same thing by attaching to a component of fungal cell membranes called ergosterol
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drugs that disrupt the cytoplasmic membrane
Azoles?
- antifungals
- harmless to humans
- prevents synthesis of ergosterol
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drugs that disrupt the cytoplasmic membrane
Polymyxin?
- effective against G-
- Pseudomonas
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drugs that inhibit metabolic pathways
Sulfonamides
- sulfa drugs
- structural analog of PABA
- is important in making folic acid
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drugs that inhibit metabolic pathways
Amantidine
- prevents uncoating of viruses
- can't replicate
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drugs that inhibit metabolic pathways
Protease inhibitors?
- inhibit protease
- is needed for HIV reproduction
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Describe actions and give examples of drugs that inhibit nucleic acid synthesis including:
Nucleotides analogs (quinolones, rifampin, AZT)?
- structurally similar to nucleotides (A, T, C, G)
- incorporated into DNA or RNA and prevent replication, transcription or translation- distort the molecules
- quinolones- prokaryotes only
- Rifampin- anti- TB drug
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What are the primary clinical considerations a doctor must consider when choosing an antimicrobial drug?
- range of pathogens against which they are effective
- efficacy, including dosages required to be effective
- routes by which they are administered
- overall safety
- side effects produced
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compare broad-spectrum drugs with narrow spectrum drugs
- broad- tetracycline, effective against G+, G-, chlamydias, rickettsias and may allow secondary infections to arise
- narrow- penicillin effective against G+ can't easily penetrate outer membrane of G-
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what factors determine the size of the zone of inhibition in the Kirby-Bauer tests?
- effectiveness of drug
- ability to diffuse
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Describe/compare the four routes of administering antimicrobial drugs.
- topically- drug applied directly, skin
- orally- simplest, but drug concentration in the body is low
- IM- intramuscular administration, slowly diffuses into blood vessels, not as high of a concentration as with IV
- IV- intravenous administration, kidneys and liver rapidly remove drug unless it is continuously administered
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describe safety and side effect including:
Toxicity?
- many drugs have toxic side effects
- kidneys, liver, nerves: polymyxin and aminoglycosides can have fatal effects on the kidneys
- have to be careful when prescribing for pregnant women
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describe safety and side effect including:
Allergies?
- may result in anaphylactic shock, which can be life- threatening
- o.1% of people are allergic to penicillin
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describe safety and side effect including:
Disruption of normal flora?
- normal flora that is unaffected by drug may overgrow, causing superinfection
- clostridium difficile in the colon causing pseudomembranous colitis, fatal
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What is antimicrobial drug resistance, and how can it be avoided?
- Microbes can become resistant: new mutations of chromosomal genes, acquiring plasmids wityh genes that confer resistance-R- plasmids
- occurs among bacteria, viruses and protozoa
- may destroy or inactivate the drug
- avoid- using high concentration of the drug for along enough time to kill all sensitive cells and inhibit others so body can defend
- use combinations of drugs
- limit the use of antimicrobials to necessary cases
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