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84 Cards in this Set
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chemotherapeutic agents |
- chemical agents used to treat disease - destroy pathogenic microbes or inhibit their growth within a host - most are antibiotics > microbial products or their derivitives that kill suceptible microbes or inhibit their growth |
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sources of antimicrobial drugs
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1. natural products from bacteria and fungi 2. synthetic products 3. semi-synthetic products - natural antibiotics modified to improve stability in the body |
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selective toxicity (definition) |
the ability of a drug to kill or inhibit a pathogen while damaging the host as little as possible
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therapeutic dose (definition)
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the drug level required for clinical treatment
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toxic dose (definition)
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the drug level at which the drug becomes too toxic for the patient (ie. produces side effects)
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therapeutic index (definition)
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ratio of toxic dose to therapeutic dose
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side effects (definition)
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undesirable effects of a drug on host cells
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narrow-spectrum drugs (definition)
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attack only a few different pathogens
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broad-spectrum drugs (definition)
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attack many different pathogens
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cidal agent
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kills microbes |
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static agent
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inhibits the growth of microbes
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measuring the effectiveness of antimicrobial drugs
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effectiveness is expressed in 2 ways: 1. minimal inhibitory concentration (MIC) 2. minimal lethal concentration (MLC) |
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minimal inhibitory concentration (definition)
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the lowest concentration of a drug that inhibits a pathogen
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minimal lethal concentration (definition)
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the lowest concentration of a drug that kills a pathogen |
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dilution susceptability tests
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- involves inoculating media containing different concentrations of a drug - the broth or agar with the lowest concentration showing no growth in the MIC - if broth is used, tubes showing no growth can be subcultured into drug-free medium > the broth from which a microbe can't be recovered is the MLC |
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disk diffusion tests
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1. disks impregnated with specific drugs are placed on agar plates inoculated with a test microbe (bacterial lawn) 2. drug diffuses from disk into agar, establishing a concentration gradient 3. observe the clear zones (no growth) around the disks (zone of inhibition) |
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the Kirby-Bauer method |
a standardized method for the disk diffusion test - the sensitivity/resistance is determined using tables relating zone diameter with microbial resistance |
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the E-test |
- convenient for use with anaerobic pathogens - similar to disk diffusion method, but uses strips rather than disks - intersection of elliptical zone of inhibition with strip indicates MIC |
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mechanisms of action of antimicrobial drugs: inhibitors of cell wall synthesis |
- most sensitive; high therapeutic index - penicillin's > most are 6-aminopenicillianic acid derivatives and differ in the side chain attached to the amino group > most crucial feature of the molecule is the B-lactam ring > essential for bioactivity > many penicillin resistant organisms produce B-lactamase (penicillinase) which hydrolyzes a bond in this ring |
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penicillins: mode of action |
1. blocks the enzyme that catalyzes transpeptidation (the formation of cross-links in peptidoglycan) 2. prevents the synthesis of complete cell walls leading to lysis of cells 3. acts only on growing bacteria that are synthesizing new peptidoglycan 4. binds to periplasmic proteins (penicillin-binding proteins aka PBP's) 5. may activate bacterial autolysins and murein hydrolases 6. stimulate bacterial holins to form holes or lesions in the plasma membrane |
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penicillin V |
- naturally occurring - narrow-spectrum |
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penicillin G |
- naturally occurring - narrow-spectrum |
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semi-synthetic penicillins |
have a broader spectrum than naturally occurring ones |
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issues with penicillin |
- resistance to penicillins, including semi synthetic analogs, continues to be a problem - roughly 1-5% of adults in the US are allergic to penicillin > the allergy can lead to a violent allergic response and death |
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cephalosporins |
- orginally isolated from the fungus Cephalosporium - structually and functionally similar to penicillins - broad-spectrum antibiotics that can be used by most patients that are allergic to penicillins |
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the 4 categories of cephalosporins (based on their spectrum of activity) |
1. cephalothin 2. cefoxitin 3. cefoperazone 4. ceftriaxone |
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vancomycin |
- glycopeptide antibiotic - inhibit cell wall synthesis - binds to the D-alanyl-D-alanine terminal sequence of peptidoglycan |
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teicoplanin |
- glycopeptide antibiotics - inhibit cell wall synthesis |
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protein synthesis inhibitors |
- many antibiotics bind specifically to the bacterial ribosome > binding can be to the 30S (small) or 50S (large) ribosomal subunit - other antibiotics inhibit a step in protein synthesis > aminoacyl-tRNA binding, peptide bond formation, mRNA reading, translocation |
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aminoglycoside antibiotics |
- large group all with a cyclohexane ring and amino sugars - bactericidal |
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aminoglycoside antibiotic mechanism |
1. bind to the 30S ribosomal subunit 2. the ribosome incorportates the incorrect amino acids 3. the protein cannot fold correctly |
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tetracyclines: structure |
all have a 4 ring structure to which a variety of side chains are attached |
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tetracyclines |
- broad-spectrum - bacteriostatic - sometimes used to treat acne |
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tetracyclines: mechanism |
1. combine with the 30S ribosomal subunit 2. inhibits binding of aminoacyl-tRNA molecules to the A site of the ribosome |
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macrolides |
contain 12- to 22-carbon lactone rings linked to one or more sugars |
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macrolides (e.g Erythromycin) |
- broad-spectrum - usually bacteriostatic - used for patients allergic to penicillin |
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macrolides (e.g Erythromycin): mechanism |
1. binds to the 23S rRNA of the 50S ribosomal subunit 2. inhibits peptide chain elongation |
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how is the mechanism by which aminoglycosides block synthesis similar to that of the tetracyclines? (3 ways) |
1. both act on the 30S subunit 2. aminoglycosides cause tRNA mismatching 3. tetracyclines block tRNA entry |
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lincosamines: mechanism |
interferes with protein synthesis in microbes |
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lincosamines are produced by |
the Streptomyces bacteria
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lincosamines antibiotic activity |
- broad-spectrum against anaerobic microbes - less activity against aerobes |
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why are lincosamines used sparingly |
they can support (indirectly) the growth of C. diff which can result in other disease states |
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chloramphenicol was originally isolated from |
Streptomyces venezuelae but is now chemically synthesized |
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chloramphenicol: mechanism |
1. binds to 23S rRNA on the 50S ribosomal subunit 2. inhibits peptidyl transferase reaction |
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when is chloramphenicol used and why |
only used in life-threatening situations because it is seriously toxic and has numerous side effects |
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metabolic antagonists act as |
antimetabolites - antagonize or block the functioning of metabolic pathways by competitively inhibiting the use of metabolites by key enzymes |
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metabolic antagonists are |
structural analogs - molecules that are structurally similar to, and compete with, naturally occurring metabolic intermediates - block normal cellular metabolism |
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sulfonamides or sulfa drugs: structure |
- structurally related to sulfanilamide, a p-aminobenzoic acid (PABA) analog > PABA is used for the synthesis of folic acid and is made by many pathogens |
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sulfa drugs are |
selectively toxic due to the competitive inhibition of folic acid synthesis enzymes |
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trimethoprim is a |
synthetic antibiotic that interferes with folic acid production |
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antibiotic activity of trimethoprim |
- broad-spectrum |
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trimethoprim can be combined with |
sulfa drugs - to increase the efficacy of the treatment - the combination blocks 2 steps in the folic acid pathway |
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side effects of trimethoprim |
1. abdominal pain 2. photo sensitivity reactions |
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nucleic acid synthesis inhibition: mechanisms |
1. block DNA replication - inhibition of DNA polymerase - inhibition of DNA helicase 2. block transcription - inhibition of RNA polymerase |
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nucleic acid synthesis inhibition |
drugs not as selectively toxic as other antibiotics because bacteria and eukaryotes do not differ greatly in the way they synthesis nucelic acids |
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quinolones |
- broad-spectrum, bactericidal, synthetic drugs containing the 4-quinolone ring |
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quinolones: mechanism |
act by inhibiting bacterial DNA-gyrase and topoisomerase II |
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antifungal drugs |
- fewer effective agents because of similarity of eukaryotic fungal cells and human cells > many have a low therapeutic index and are toxic - fungi are able to degrade many compounds including drugs - it is easier to treat superficial mycoses than systemic infections |
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treating superficial mycoses (ex. Candida, atheletes foot) |
- topical and oral - mechanisms: 1. disrupts membrane permeability and inhibit sterol synthesis 2. disrupts mitotic spindle; may inhibit protein and DNA synthesis |
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treating systemic mycoses |
- difficult to control and can be fatal - 3 common drugs: 1. amphotericin B > binds sterols in membrane 2. 5-flucytosine > disrupts RNA functions 3. fluconazole |
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treating mycoses: amphotericin B |
1. binds to ergosterol and damages membranes 2. administered orally 3. stays in suspension 4. poorly absorbed 5. stable in GI tract 6. for GI tract infections |
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treating mycoses: nystatin |
1. binds to ergosterol and damages membranes 2. administered IV 3. serious side effects 4. for systemic infections |
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antiviral drugs: drug development |
- drug development has been slow because it is difficult to specifically target viral replication - drugs currently used inhibit virus-specific enzymes and life cycle processes
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antiviral drugs: amantidine |
- used to prevent influenza infections - blocks penetration and uncoating of influenza virus |
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antiviral drugs: adenine arabinoside (vidarabine) |
- inhibits herpes virus enzymes involved in DNA and RNA synthesis and function |
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antiviral drugs: tamiflu |
- anti-influenza agent - a neuraminidase inhibitor > essential for release of new particles from infected cell - not a cure - leads to resistant viruses - prescribed prophylactically |
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anti-HIV drugs: azidothymidine (AZT) |
nucleoside reverse transcriptase inhibitors |
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anti-HIV drugs: ritonavir |
- viral protease inhibitor > mimic peptide bond that is normally attacked by the protease |
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anti-HIV drugs: fusion inhibitors |
prevent HIV entry into the cell |
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most effective HIV drugs |
drug cocktails to curtail resistance |
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1. infection begins with HIV fusion |
fusion inhibitors block this step |
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2. once inside a host cell, HIV uncoats and its reverse transcriptase forces the host to make DNA from the viral RNA |
RT inhibitors block this step |
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3. the viral DNA is transcribed and translated into a linear polypeptide that is cut to release viral proteins |
protease inhibitors block this step |
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4. viral DNA is added to the host DNA by the action of a viral integrase |
integrase inhibitors block this step |
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why is malaria, like AIDS, now treated with several drugs simultaneously? |
many strains of the malaria parasite are resistant to drugs that used to be effective. Now single drugs are no longer effective. Furthermore, the use of multiple drugs require multiple mutations to occur simultaneously which is hoped to reduce the chance of resistance of occurring again |
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antiprotozoan drugs: mechanism |
the mechanism of antiprotozoan drugs is not known |
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what special considerations must to taken into account when treating infections caused by protozoan parasites? |
protozoan parasites are geographically endemic, and each variety may need it's own drug |
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ability of a drug to reach the site of infection depends on: |
mode of administration: oral, topical, or parenteral (non oral) |
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factors influencing the ability of a drug to reach concentrations exceeding the MIC |
1. amount administered 2. route of administration 3. speed of uptake 4. rate of clearance (elimination) from the body |
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drugs resistance is an increasing problem because... |
1. once resistance originates in a population, it can be transmitted to other bacteria 2. a particular type of resistance mechanism is not confirmed to a single class of drugs |
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drug resistance mutants arise... |
spontaneously and are then selected |
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microbes in ______ or ______ may be growing ______ and not be _______ |
abscesses, biofilms, slowly, susceptible |
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development of a resistant strain of bacteria |
1. a population of microbial cells that contains both drug-sensitive cells and drug-resistant cells is exposed to the drug 2. drug-sensitive cells are inhibited by the exposure to the drug 3. the remaining drug-resistant cells grow over time 4. resulting in a population of (mostly) drug-resistant cells |
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overcoming drug resistance |
1. give drug in appropriate concentrations to destroy susceptible 2. give 2 or more drugs at the same time 3. use drugs only when necessary |