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Flashcards in CH 9 antimicrobial chemotherapy Deck (33):
1

Chemotherapeutic Agents

-Chemical agents used to treat disease
-Antimicrobial chemotheraputic agents: antibacterial, antiviral, antifungal, antiprotozoan

2

Antimicrobial chemotherapy

-destroy or inhibit the growth of pathogens
-concentrations low enough not to damage host

-include antibiotics--microbial products or derivatives

3

Paul Ehrlich

-Magic Bullet--chemical that would specifically target the pathogen
-Trypan Red dye used against trypanosomes, stain that kills cells

-Arsephenamine (Salvarsan) used to treat syphilis. arsenic derviative

4

Gerhard Domagk

-Protonsil Red dye effective against pathogenic strepto/stahylococci
-Metablolized by the body to produce sulfailamide

-lead to production of sulfa drugs

-nobel prize in medicine in 1939

5

Alexander Fleming

-Rediscovered penicillin after Ernest Duchesne
-Penicillum notatum--fungus effective for inhibiting microbial growth

-Florey, Chain, Heatley developed method for producing and purifying penicillin

-Nobel prize in medicine in 1945

6

Selman Waksman

-Discovered streptomycin
-First treatment for TB

-Steptomyces griseus--fungus

-lab went on to discover more antibiotics--neomycin and actinomycin

-nobel prize in medicine in 1952

7

Selective Toxicity

-Drug is more toxic to the pathogen than it is to the host
-Drugs that specifically target microbial functions that do not occur in host cells have greater selective toxicity

8

Therapeutic Dose

level required to treat infection

9

Toxic Dose

Level at which drug becomes toxic to host

10

Therapeutic Index

Ratio of toxic dose to therapeutic dose

11

Range of effectivenes

-Narrow-spectrum--effective against a limited number of species
-broad-spectrum--effective against a variety of species, gram negative and gram positive agents, tetracycline--effective against most bacteria

12

Narrow Spectrum vs. broad-spectrum

-broad--used w/out knowing ID of microbe, greater effect on normal microflora, but can lead to superinfection--growth of resistant microbes

13

natural anitbiotics

syn. by microbes

14

Semi-synthetic antibiotics

-Chemically modified derivatives of natural products
-less susceptible to inactivation

-generally have a borader spectrum

15

Completely synthetic drugs

sulfa drugs, antivirals

16

cidal vs static

-Cidal--kills the pathogen
-Static--inhibits pathogen growth, immune system eliminates infection

-cidal drugs are often static at low concentrations

17

Ideal antimicrobial drug

-selectively toxic to the pathogen but nontoxic to host cells
-micrbicidal

-relatively soluble

-readily delivered to site of infection

-remains active in the body

-not prematurely broken down or excreted

-doesn't lead to drug resistance

-reasonably priced

18

Treatment vs. Prophylaxis

-Treatment--antimicrobial agents are used to combat an existing infection
-prophylaxis--antimicrobial agents used to prevent infection

19

Measuring Effectiveness

-Minimal inhibitory concentration (MIC)--lowest [] that inhibits pathogen growth, not growth after 16-20 hours
-minimal lethal [] (MLC)--lowest [] that kills pathogen

20

dilution susceptiblily tests

-expose microbes to different [] of the antimicrobial agent
-measure growth

-can determine MIC or MLC after subculturing

-liquid or agar cultures

21

disk diffusion test

-Kirby-Bauer test for antibiotic susceptibility
-filter disks impregnated with antibiotics are placed on agar previously inoculated with bacterial sample

-antibiotic diffuses into the medium, creating a [] gradient

-zone of clearing around the disk means the bacteria is inhibited by the antibiotic--wider clear zone=more susceptible, zone width also dependent on initial [] of antibiotic, solubility, and rate of diffusion

22

Factors Affecting Drug Effectiveness

-drug must reach site of infection
-[] must exceed MIC

-pathogen must be susceptible

23

Route of Administration

-Enteral--systemic affect, given via digestive tract
-parenteral (shots, IV/IM, enters circulatory system)--systemic affect, given by routes other than digestive tract, penicillin G sensitive to stomach acid, aminoglycosides not absorbed will in the intestine

-topical--local effect, applied where drug action is required, antibiotic ointment, eye drops, ear drops, some antibiotics are so toxic they can only be used topically (neomycin, bacitracin)

24

Factors Affecting Drug Transport

-Hard to get drug to the infection site
-Poor circulation
-blood clots
-necrosis--staph or gangreen infection

-blood-brain barrier--inject into cerebral fluid via spinal cord

-biofilms--protective coating, knee-replacements and etc. prime target

25

Factors Affecting Drug []

-Amount of drug administered (oral lowest, topical highest)
-route of administration (oral, intravenously, topical)

-speed of uptake (enteral-how well absorbed)

-chemical break-down and excretion (personalized medicine)

-extended release drugs (maintain constant release level)

26

Pathogen Susceptibility

-actively growing bacteria are more susceptible (exponential phase)
-sensitivity of the pathogen to specific agent

27

Mechanisms of Drug Resistance--cell wall, pumps, inactivation

-Drug unable to enter the cell wall--outer membrane of gram neg., Mycobaterium cell wall, lack binding or transport proteins, capsules
-Efflux pumps remove drugs from cell--nonspecific, multi-drug resistance

-Inactivation of the drug--Degradation (penicillinase), chemical modification (chloramphenicol, aminoglycosides)

28

Mechanisms of Resistance--modify, alternate paths

-modification of the target (change so drug doesn't affect it but bacteria still functions)--vancomycin resistance-convert D-Ala to D-lactate/serine, change 23sRNA sequence--resistance to erythromycin and chloramphenicol

-Develop alternate pathways--cirumvent pathway blocked by antibiotic, bacteria resistnat to soulfa drugs have other ways of obtaining Folic acid

29

Development of Drug resistance

-Spontaneous mutations--alter drug target
-selection for drug resistant cells--kills nonresistant, resistant ones multiply and now they are all resistant to drug, so must have high enough dose to kill them all and take for long enough period of time

30

Transfer of Drug Resistance

-Resistance genes are often found on plasmids--R plasmids, may carry genes for resistances to several drugs
-also found on bacterial chromosome, transposons, and integrons--will get rid of resistant genes if not challeneged often

-easily transferred through horizontal gene transfer

-food agriculture is increasing drug resistance because 75% of animals are given human antibiotics

31

bacteria sharing genes-horizontal gene transfer

-Conjugation--sex pilus, F+-->F-
-Transformation--pick up DNA from environment

-Transduction--bacteriophage transfer of viral DNA

32

Counteracting drug resistance

-Increase drug []--less antibiotic with higher dose to destroy susceptible cells and spontaneous mutants
-take full course antibiotics

-use multi-drug cocktail

-use narrow-spectrum drugs

-don't give antibiotics to viral infections, only use when necessary

33

Phage therapy

-using bacteriophages to treat bacterial diseases
-only targets one type of bacteria, but must know infecting bacteria and the type of bacteriophage specific to it
-more specific then drugs

-easier to overcome resistance