Chapter 12 Flashcards

1
Q

goal of antimicrobial therapy

A

administer a drug to an infected person that destroys the infective agent without harming the host’s cells

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2
Q

Characteristics of Ideal Antimicrobial drug(natural/synthetic)
antibiotics- common metabolic products of aerobic bacteria/fungi
bacteria-streptomyces + bacillus
molds- penicillum + cephalosporium

A
  • 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
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3
Q

selective toxicity

A

-more difficult as characteristics of infectious agent become more similar to the vertebrae host cell, creating more side effects

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4
Q

narrow and broad spectrum

A
  • narrow, penicillin

- broad target most common components of pathogens(ex. ribosomes)

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5
Q

Antimicrobial drugs that affect the bacteria cell wall

A
  • 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
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6
Q

Antimicrobial drugs that disrupt cell membrane function

A
  • 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
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7
Q

Drugs that affect nucleic acid synthesis(DNA/RNA)

A
  • 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)
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8
Q

Drugs that block protein synthesis

A
  • 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
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9
Q

Antimicrobial drugs that affect metabolic pathways (competitive inhibition through metabolic analog)

A

SULFONAMIDES+ TRIMETHOPRIN-block enzymes required for tetrahydrofolate synthesis needed for DNA/RNA synthesis(can attack mitochondria causing bone marrow issues)

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10
Q

Antibacterial drugs that act on the cell wall(cephalosporins/penicillin)

A
  • 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

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11
Q

Additional Beta-lactams

A

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

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12
Q

Non Beta-lactam Cell Wall Inhibitors

A

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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13
Q

Drugs that Act on DNA or RNA

A

fluoroquinolones-broad-spectrum effectiveness, bind to DNA gyros, CDC monitoring use to prevent ciproflaxin resistant bacteria

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14
Q

Drugs that interfere with protein synthesis

A

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

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15
Q

Drugs that block metabolic pathways

A
  • 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
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16
Q

Newly Develop classes of antimicrobials

A

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

17
Q

Agents to treat fungal infections(fungal cells are eukaryotic, a drug that is toxic to fungal cells is also toxic to humans cells)

A

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
18
Q

Antimalarial drugs
Anti protozoan drugs
antihelminthic drugs

A
  • 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
19
Q

Antiviral chemotherapeutic agents

A

-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

20
Q

Drugs for treating influenza

A
  • 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
21
Q

Anti-herpes drugs

A
  • 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
22
Q

Drugs for trading HIV infections and aids

A

-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

23
Q

Anti-HIV drug actions(interferon)

A
  • 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
24
Q

The acquisition of drug resistance(natural selection)

A
  • 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
25
Q

Interactions between Drug and Host

A
  • 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)
26
Q

Considerations in selecting an antimicrobial drug

A
  • 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