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The greatest number of antibiotics are derived from the following: (four)
- Streptomyces (bacterium)
- Bacillus (bacterium)
- Penicillium (fungi)
- Cephalosporium (fungi)
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Semi-Synthetics
chemically altered antibiotics that are more effective than naturally occuring ones
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Synthetic Antibiotics
Antimicrobials that are completely synthesized in a lab
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Prophylaxis
- use of a drug to prevent imminent infection of a person at risk
- not for use after the disease has occured
- same as therapeutic drugs except in smaller dose
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Narrow Spectrum
only effective against a very limited range of bacteria
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Broad Spectrum
- targets something that is common between all different microbes
- effect against a wide variety of microbes
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Selective Toxicity
ability of an antimicrobial or drug to kill a microorganism but not harm the host (person)
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Characteristics of Ideal Antimicrobial Drug
- Selective Toxicity
- microbicidal (kill) rather than microbistatic (inhibits growth)
- relatively soluble
- remains potent long enough to work
- doesn't lead to resistance
- assists host's defenses
- readily delivered to site of infection
- reasonably priced
- doens't disrupt host's health (allergies or other infections)
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Mechanisms of action of Microbial Drugs
- Inhibition of Cell Wall synthesis
- Inhibition of Protein synthesis
- Disruption of cytoplasmic membrane
- Inhibition of general metabolic pathway
- Inhibition of DNA or RNA synthesis
- Inhibition of pathogens attachment to, or recognition of host
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Inhibiton of Cell Wall synthesis
- most common prevent cross-linkage of NAM subunits (beta-lactams)
- bacteria have weekened cell walls and lyse
- Beta-lactams
- Vancomycin and cycloserine
- Isoniazid and ethambutol
- prevent bacteria from increasing amount of peptidoglycan, has no effect on existing layer, effective for only growing cells
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Beta-Lactams
- more active aginst more types of bacteria
- more stable in acidic enviroments
- more readily absorbed
- less susceptible to deactivation
- **Simple beta lactams: Monobactams: effective only against gram-negatives
- inhibit the last step in PGN synthesis, the transpeptidation reaction that cross-links the peptide side-chains of the polysaccharide-peptidoglycan backbone
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Vancomycin and Cycloserine
interfere with particular bridges that link NAM subunits in many gram-posBacitracin- blocks secretion of NAG and NAM from cytoplasm
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Isoniazid and ethambutol
Disrupt mycolic acid formation in mycobacterium species
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Bacitracin
prevents the linkage of NAG and NAM and blocking their secretion from cytoplasm by binding the lipid carrier bactoprenol and preventing its dephosphorylation
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Phosphonomycin
blocks the conversion of UDP-NAG to UDP-NAM by blocking pyruvyl transferase
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Cycloserine
inhibits the activity of enzymes that add alanines to peptide side-chain
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Vancomycin
inhibits both transglycosylation (NAM is attached to the NAG) and transpeptidation
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Inhibiton of Protein Synthesis
- prokaryotic ribosome are 70S (30S and 50S)
- eukaryotic ribosomes are 80S (40S and 60S)
- Drugs: Aminoglycosides, tetracyclides, chloramphenicol, lincosamides, streptogramins, macrolides, fomiversen, oxazolidinones
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Aminoglycosides
- cause change in 30S shape
- mRNA is misread
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Tetracycline
- block docking site of tRNA
- blocks the A site of 30S
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Chloramphenicol
blocks enzyme activity of the 50S subunit, preventing the formation of peptide bonds between AA
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Streptogramins
- lincosamides or macrolides bind to 50S subunit, blocking proper mRNA movement through ribosome.
- synthesis stops
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Formiversen
blocks ribosomal sub units from attaching to mRNA
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Oxazolidinone
- blocks initiation of translation
- doesnt allow attachment
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Disruption of Cytoplasmic membranes
- some drugs from channels through cytoplasmic membrane and damage it's integrity
- nystatin and amphotericin B attach to ergosterol in fungal membranes
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Azoles
- disruption of cyto membrane
- inhibits ergosterol synthesis
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Polymyxin
- disrupts cytoplasmic membranes of gram-negatives
- toxic to human kidneys, because of this not prescribed often
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Pyrazinamide
disrupts transport across cytoplasmic membrane of M.tuberculosis (very unique for treatment because most drugs act on mycolic acid)
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Parasitic Drugs: praziquantel and ivermectin
act against cytoplasmic membranes by changing the permeability
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Inhibition of metabolic pathways
- antimetabolic agents can be effective when pathogen and host's metabolic processes differ
- Quinolones interfere with metabolism of malaria
- heavy metal inactivates enzymes
- drugs block activation of viruses
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Inhibition of Nucleic Acid synthesis
- several drugs block DNA replication and mRNA transcription
- drugs often affect both euk and prokaryotic cells
- not normally used to treat infections
- used in reseach and perhaps to slow cancer cell replication
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Nucleotide Analogs
- intefere with function of nucleic acids
- distort shapes of moleucles and prevent further replication, transcription, or translation
- most often used against viruses
- effective against rapidly dividing cancer cells
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Reverse transcriptase inhibitors
- act against an enzyme HIV uses in it's replication cycle
- do not harm people because humans lack reverse transcriptase
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Metronidazole
when the nitro group enters the cells, it is reduced in the cytoplasm and forms cytotoxic compounds that disrupts the bacterial or protozoan DNA
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Minimum inhibitory concentration test
- multiple tubes with increasing concentraion of antimicrobial
- lower concentration will become turbid
- first clear tube: will be minimum inhibitor
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Minimum bactericidal concentration test
the concentration of the drug that was MIC (minimum inhibitory concentration) is innoculated on plate along with increasing concentrations to see whether bacterial colonies grew or not.
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Routes of Administration
- Oral- requires no needles, self administered, takes longer
- Intramuscular- via needle, takes a while to travel from muscle to bloodstream (not good for emergency)
- Intravenous-delivers drugs directly to bloodstream
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