Chapter 12 Flashcards
goal of antimicrobial therapy
administer a drug to an infected person that destroys the infective agent without harming the host’s cells
Characteristics of Ideal Antimicrobial drug(natural/synthetic)
antibiotics- common metabolic products of aerobic bacteria/fungi
bacteria-streptomyces + bacillus
molds- penicillum + cephalosporium
- selectively toxic to the microbe but nontoxic to host cells
- microbicidal rather than microbistatic
- remans potent long enough to act and is not broken down or excreted prematurely
- is not subject to the development of antimicrobial resistance
- complements or assists the activities of the host’s defenses
- remains active even when diluted in body fluids and tissues
- readily delivered to the site of infection
- reasonably priced
- does not disrupt the host’s health by causing allergies or perdisposing the host to other infections
selective toxicity
-more difficult as characteristics of infectious agent become more similar to the vertebrae host cell, creating more side effects
narrow and broad spectrum
- narrow, penicillin
- broad target most common components of pathogens(ex. ribosomes)
Antimicrobial drugs that affect the bacteria cell wall
- most bacterial cell walls contain peptidoglycan
- penicillins and cephalosporins block synthesis of peptidoglycan
- Active on Young, growing cells, can cross cell walls of gram-negative bacteria
- PENICILLIN
- CEPHALOSPORIN
- VANCOMYCIN
- BACITRACIN
- MONOBACTAMS/CARBAPENEMS
- FOSFOMYCIN
- CYCLOSERINE
- ISONIAZID
Antimicrobial drugs that disrupt cell membrane function
- cells with damaged membranes die from disruption in metabolism or lysis
- these drugs have specificity for a particular microbial group, based on lipid differences in cell membranes
- POLYMYXINS-interact with phospholipids and cause leakage
- amphotericin B + nystatin-form complexes with sterols on fungal membranes which cause leakage
Drugs that affect nucleic acid synthesis(DNA/RNA)
- Block synthesis a nucleotides, inhibit replication, or stop transcription
- CHLOROQUINE-binds and cross-links the double helix
- QUINOLONES- inhibit DNA helicases
- antiviral drugs that are analogs(fakes) of purines and pyrimidines insert in viral nucleic acid, preventing replication
- RIFAMPIN(inhibit RNA polymerase)
Drugs that block protein synthesis
- attack ribosome synthesis, can also damage eukaryotic mitochondria(similar ribosomes features w/prokaryotes)
- AMINOGLYCOSIDES(STREPTOMYCIN/GENTAMYCIN)-insert and cause misreading of mRNA
- TETRACYCLINES-Block attachment of tRNA on the A acceptor site, stopping synthesis
- and LINZOLID, CHLORAMPHENICOL, ERYTHROMYCIN, CLINDAMYCIN, STREPTOGRAMIN
Antimicrobial drugs that affect metabolic pathways (competitive inhibition through metabolic analog)
SULFONAMIDES+ TRIMETHOPRIN-block enzymes required for tetrahydrofolate synthesis needed for DNA/RNA synthesis(can attack mitochondria causing bone marrow issues)
Antibacterial drugs that act on the cell wall(cephalosporins/penicillin)
- beta-lactam group-
- interfere with cell wall synthesis
- most are penicillin and cephalosporins
-Penicillin-can be synthesized in the lab, more economical through microbial fermentation,
CONSISTS OF THREE PARTS
-thiazolidine ring
-beta-lactam ring
-variable side chain dictating microbial actiivity
-G/V most important natural forms
-drug of choice for gram+ cocci(streptococci) + some gram- (meningococcal/syphilis spirochete)
-resistant synthetic penicillin- methicilin, nafcillin, coxacillin
-problems-allergies/resistance
-synthetic penicillin-resistant to penicillinase/more broad spectrum
Cephalosporins
-4 gens, each one more effective against gram-, less side effects/better dosing
Additional Beta-lactams
Carbapenems
-imipenen- broad spectrum drug for infections with aerobic and anaerobic pathogens, low-dose, administered orally with few side effects
Monobactams
-aztreonam- narrow spectrum drug for infections by gram-negative aerobic bacilli, may be used by people allergic to penicillin
Non Beta-lactam Cell Wall Inhibitors
Vancomycin-narrow spectrum, most effective in treatment of staphylococcal infections in cases of P+M resistance,p allergic reaction, toxic/hard to administer
-Bacitracin- narrow spectrum made by a strain of Bacillus Subtitles, topical ointment
-Isoniazoid(INH)- works by interfering with mycolic acid synthesis, used to treat infections w/ M. tuberculosis
-Polymixins- narrow spectrum peptide antibiotics with a unique fatty acid component(treat drug-resistant P. aeruginosa/severe UTI)
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Drugs that Act on DNA or RNA
fluoroquinolones-broad-spectrum effectiveness, bind to DNA gyros, CDC monitoring use to prevent ciproflaxin resistant bacteria
Drugs that interfere with protein synthesis
Aminoglycosides
-broad spectrum, inhibit protein synthesis, useful against aerobic gram-negative rod’s/ Plus certain Graham positive bacteria, streptomycin(plague/TB/tularemia), gentamicin(less toxic, use against gram- rods)
Tetracycline antibiotics
-broad, block protein synthesis by binding to ribosomes
-treat std, lyme, typhus, acne, protozoa, rocky mountain
-chloramphenicol-broad, blocks protein synthesis/peptide formation, chemically synthesized, very toxic, can cause bone marrow damage, used on typhoid/rickettsia/chlamydia/brain abscesses
Macrolides/related antibiotics
-erythromycin- broad, low toxicity, for penicillin resistant, for mycoplasma pneumonia/legionella/chlymadia/pertussis/diptheria/prophylatic before surgery
-newer forms clarithromycin/azithromycin
Drugs that block metabolic pathways
- Most are synthetic
- sulfonamides-1st animicrobic drugs
- Narrow spectrum, block synthesis of folic acid
- sulfisoxazole-shigellosis, UTI, protozoan infections
- silver sulfadiazine- burns/eye infections
- trimethroprim-combo w. sulfamethoxazole-UTI/PCP
Newly Develop classes of antimicrobials
Fosfomycin trimethamine- phosphoric acid effective as alternate treatment for UTIs, inhibits cell wall synthesis
Synercid- effect against staphylococcus/enterococcus that cause endocarditis/surgical infections, used when bacteria is resistant to other drugs, inhibits protein synthesis
Daptomycin- Direction mainly against gram positive, disrupt membrane function
Ketolides- telitromycin(ketek), new drug with different ring structure from erythromycin, used for infection when resistant to macrocodes
Oxazolidinones- linzolid(Zyvox), synthetic antimicrobial that the interaction of mRNA and ribosome
-used to treat methicillin-resistant Staphylococcus areus and vancomycin resistant enterococcus
Agents to treat fungal infections(fungal cells are eukaryotic, a drug that is toxic to fungal cells is also toxic to humans cells)
Five antifungal groups
- macrolide polyene-amphotericin B- mimic lipids,treats systemic/topical, versatile, nystatin(topical)
- griseoflavin- stubborn cases of dermatophyte infections, nephrotoxic
- synthetic azoles- broad spectrum, ketoconazole, clotrimazole, miconazole
- flucytosine- analog of cytosine, cutaneous mycoses/ combo w/ amphotericin B for systemic mycoses
- echinocandins- damage cell walls, capsofungi
Antimalarial drugs
Anti protozoan drugs
antihelminthic drugs
- quinine, chloroquinine, primaquine, mefloquine
- metronidazole, quinicrine, sulfonamides, tetracyclines
- immobilize, disintergrate or inhibit metabolism
- -mebendazole thiabendazole- broad, inhibit function of microtubules, it Interferes with glucose utilization and disables them
- -pyrantel, piperazine- paralyze muscles
- -niclosamide- destroys scolex
Antiviral chemotherapeutic agents
-Selective toxicity is almost impossible due to obligate intracellular parasitic nature of viruses
-Block penetration in the host cell
-Block replication, transcription, or translational viral genetic material
Nucleotide analogs
-acyclovir- herpes
-ribavirin-guanine analog- RSV, hemorhagic fevers
-AZT- thymine analog- HIV
Prevent maturation of viral particles
–Protease inhibitors-HIV
Drugs for treating influenza
- Amantadine/ rimantadine- restricted almost exclusively to influenza a viral infections, prevent fusion virus for cell membrane
- relenza/tamiflu-slightly broader spectrum, Blocks neuraminidase in influenza a and B
Anti-herpes drugs
- Many antiviral agents mimic the structure of nuclear tides and compete for sites on replicating DNA
- -Acyclovir(Zovirax), Valacyclovir(Valterx), Famiciclovir(Famvir), Peninciclovir(Denavir)
- -Oral and topical treatments for oral genital herpes, chickenpox, and shingles
Drugs for trading HIV infections and aids
-Retro virus offers two targets for chemo therapy
-Interference with viral DNA synthesis from viral RNA using nucleoside reverse transcriptase inhibitors(nucleotide analogs)
-interference with synthesis of DNA using non-nucleoside reverse transcriptase inhibitors
Azidothymidine(AZT)-first drug aimed at treating aids, thymine and analog
Anti-HIV drug actions(interferon)
- Human based glycoprotein produced primarily by fibroblasts and leukocytes
- Therapeutic benefits include:
- -Reduces healing time and some competitions of infections
- -Prevents or reduces symptoms of cold and papilloma virus
- -Close the progress of certain cancers, leukemias, and lymphomas
- -Treatment of hepatitis C, genital warts, Kaposi’s sarcoma
The acquisition of drug resistance(natural selection)
- Adaptive response with microorganisms begin to tolerate an amount of drug that would ordinarily be inhibitory, Due to genetic versatility or variation, Intrinsic or acquired
- conjugation, transformation, transduction
- Acquired resistance
- -Spontaneous mutations in critical chromosome of genes
- -Acquisition of new genes or sets of genes via transfer from another species
- -originates from resistance factors(plasmids) encoder with drug resistance, transposons
Interactions between Drug and Host
- estimate at 5% of all persons taken antimicrobials will experience a serious adverse reaction to the drug(side effects)
- Major side effects
- -Direct damage to tissue due to toxicity of drug
- -Allergic reaction
- -Disruption in the bounds of normal flora(create super infections)
Considerations in selecting an antimicrobial drug
- Identify the micro organism caused the infection
- test the microorganisms susceptibility to various drugs
- The overall medical condition of the patient
Essential for groups of bacteria commonly shined resistance
–Kirby-Bauer disk diffusion test
– E-test diffusion test
–Dilution tests- (MIC) minimum inhibitory concentration smallest concentration of drug that visibly inhibits growth
Comparing MIC for common drugs and pathogens
-In vitro activity of the drug is not always correlated with in vivo
–If therapy fails, different drugs, combination drugs, our different administration must be considered
-Best to choose a drive with highest level selectivity of the lowest level toxicity(therapeutic index)
-High index is desirable
