CH 9 antimicrobial chemotherapy Flashcards
CH 9
Chemotherapeutic Agents
- Chemical agents used to treat disease
- Antimicrobial chemotheraputic agents: antibacterial, antiviral, antifungal, antiprotozoan
CH 9
Antimicrobial chemotherapy
- destroy or inhibit the growth of pathogens
- concentrations low enough not to damage host
-include antibiotics–microbial products or derivatives
CH 9
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
CH 9
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
CH 9
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
CH 9
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
CH 9
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
CH 9
Therapeutic Dose
level required to treat infection
CH 9
Toxic Dose
Level at which drug becomes toxic to host
CH 9
Therapeutic Index
Ratio of toxic dose to therapeutic dose
CH 9
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
CH 9
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
CH 9
natural anitbiotics
syn. by microbes
CH 9
Semi-synthetic antibiotics
- Chemically modified derivatives of natural products
- less susceptible to inactivation
-generally have a borader spectrum
CH 9
Completely synthetic drugs
sulfa drugs, antivirals
CH 9
cidal vs static
- Cidal–kills the pathogen
- Static–inhibits pathogen growth, immune system eliminates infection
-cidal drugs are often static at low concentrations
CH 9
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
CH 9
Treatment vs. Prophylaxis
- Treatment–antimicrobial agents are used to combat an existing infection
- prophylaxis–antimicrobial agents used to prevent infection
CH 9
Measuring Effectiveness
- Minimal inhibitory concentration (MIC)–lowest [] that inhibits pathogen growth, not growth after 16-20 hours
- minimal lethal [] (MLC)–lowest [] that kills pathogen
CH 9
dilution susceptiblily tests
- expose microbes to different [] of the antimicrobial agent
- measure growth
- can determine MIC or MLC after subculturing
- liquid or agar cultures
CH 9
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
CH 9
Factors Affecting Drug Effectiveness
- drug must reach site of infection
- [] must exceed MIC
-pathogen must be susceptible
CH 9
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)
CH 9
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
