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CONTROLLING MICROBIAL GROWTH IN THE BODY - Coggle Diagram
CONTROLLING MICROBIAL GROWTH IN THE BODY
HISTORY OF ANTIMICROBIAL AGENTS
Alexander Fleming: developed earliest form of penicillin from
Penicillium,
an antibiotic (antimicrobial produced naturally by organisms)
Gerhard Domagk: developed sulfanilamide, the first antimicrobial agent used to treat wide array of infections
Paul Ehrlich: "magic bullets;" produced arsenic compound that killed trypanosomes (protozoa) and another that worked against treponemes (syphilis)
RESISTANCE TO ANTIMICROBIAL DRUGS
mechanisms of resistance:
microbes may resist a drug by 1 of at least 7 mechanisms:
altering the cell's metabolic pathways
pumping the drug out of the cell
altering the drug's receptor to prevent binding
biofilms retard drug diffusion and alter metabolic rates, reducing the effectiveness of antimicrobials
inducing chnages in the cell membrane to prevent entry of the drug
protecting the target of an antimicrobial drug to inhibit its binding
producing enzymes such as beta-lactamase that deactivate the drug
multiple resistance & cross resistance: pathogen can acquire resistance to more than one drug at a time; when R-plasmids exchanged
superbug: pathogens that are resistant to most antimicrobial agents
cross resistance: occurs when drugs are similar in structure
development of resistance in populations: some are naturally, partially, or completely resistant;
can be acquired in 2 ways:
acquiring resistance genes on extrachromosomal pieces of DNA called R-plasmids
through new mutations of chromosomal genes
retarding resistance: resistance
can be retarding in 1 or more of 4 ways:
using sufficiently high concentrations of a drug for sufficient length of time to kill all sensitive cells and inhibit other enough for body to destroy them
using antimicrobials in combination that results in efficacy that exceeds the efficacy of the drugs alone
limiting the use of antimicrobials to necessary cases, avoiding indiscriminate use
developing new variations of existing drugs
MECHANISMS OF ANTIMICROBIAL ACTION:
key is selective toxicity; antibacterial drugs constitute most antimicrobial agents; fewer drugs to treat eukaryotic infection; even fewer antivirals
disruption of cytoplasmic membranes: drugs attack fungi, Gram (-) bacteria, and some parasites
gramicidin & polyenes: disrupt the cytoplasmic membrane of a targeted cell by forming a channel through the membrane and damaging its integrity
polyenes nystatin & amphotericin B: (fungicidal); attach to ergosterol, a lipid in fungial membranes
azoles & allylamines: (antifungal drugs); inhibit the synthesis of ergosterol
polymyxin: effective against Gram (-) bacteria, but toxic to kidneys; reserved for use against external pathogens that are resistant
inhibition of metabolic pathways: agents target differences between metabolic processes of a pathogen and its host
sulfonamides: structural analogs of PABA, a compound crucial in DNA & RNA synthesis in some microorganisms; substitution of drug in the metabolic pathway prevents to nucleic acid synthesis
antiviral drugs: neutralize the acidic environment of phagolysosomes and prevent viral uncoating
trimethoprim: binds to enzyme involved in conversion of dihydrofolic acid to THF, thereby preventing DNA synthesis and replication
inhibition of protein synthesis: targets bacterial protein translation
aminoglycosides & tetracycline: inhibit functions of the
30S
ribosomal subunit
aminoglycosides: cause 30S shape so mRNA is misread
tetracycline: blocks docking site of tRNA
chloramphenicol & macrolides: inhibit functions of the
50S
ribosomal subunit
chloramphenicol: binds to 50S subunit
macrolides: binds to 50S subunit so mRNA cannot move through ribosome properly
inhibition of nucleic acid synthesis: block either DNA replication or DNA transcription into RNA
nucleotide/nucleoside analogs: incorporated into DNA/RNA of pathogens; they distort the shapes of nucleic acid molecules to prevent replication, transcription, or translation; often used for viruses and cancer cells
synthetic quinolones/fluoroquinolones: active against prokaryotic DNA because they inhibit DNA gyrase, an enzyme needed for coiling of replicating DNA
reverse transcriptase inhibitors: act against reverse transcriptase, an enzyme that HIV uses to replicate
inhibition of cell wall synthesis: causes cell wall to weaken to the point of osmotic lysis
vancomycin, cycloserine: disrupt cell wall formation by interfering with alanine-alanine bridges that link NAM subunits in Gram (+) bacteria
bacitracin: disrupts cell wall formation by blocking the secretion of NAG and NAM from cytoplasm to cell wall
penicillin, cephalosporin, monobactam: act by preventing cross-linkage of NAM subunits; beta-lactams (functional groups in the antimicrobials) bind to enzymes to cross-link NAM subunits
isoniazid (INH), ethambutol: block mycolic acid synthesis in walls of mycobacteria (treats tuberculosis & leprosy)
echinodandins: block key component in cell walls of fungal cells
prevention of virus attachment: attachment is blocked by peptide and sugar analogs of attachment or receptors proteins
EVALUATION OF ANTIMICROBIAL: ideally antimicrobial agent should be
readily available, inexpensive, chemically stable, easily administered, nontoxic, selectively toxic
efficacy: determined by dosages required to be effective, routes of administration, and overall safety
minimum inhibitory concentration test: attempts to quantify the smallest amount of a drug that will inhibit a pathogen
minimum bactericidal concentration test: extension of MIC test in which samples taken from clear MIC tubes are monitored for bacterial replication
diffusion susceptibility test: used to reveal which drug is most effective against a particular pathogen; in general, the larger the zone of inhibition around a disk, the more effective the drug
routes of administration: in order to determine, must know how the antimicrobial agent will be distributed; site of infection must also be considered
topical application: used for external infections
used for internal infections:
intramuscular: requires needle; concentration never as high as IV
intravenous: requires needle or catheter; drug concentration diminishes as liver/kidneys remove from circulation
oral: simplest; lower drug concentration; no reliance for health care provider; patients do not always follow prescribing info
spectrum of action: broad-spectrum allow for secondary or superinfections to develop; killing of normal flora reduces microbial antagonism
safety and side effects: must consider the possibility of adverse side effects of drug therapy
allergies: rare but can be life-threatening; can cause anaphylactic shock
disruption of normal microbiota: may result in secondary infections; overgrowth of normal flora causes superinfections
toxicity: exact cause is poorly understood; drugs may be toxic to kidney, liver, nerves; considered needed when prescribing drugs to pregnant women