Lesson 8: Introduction to Chemotherapy

chemotherapy

refers to the use of drugs or chemicals to treat or prevent dss caused by infectious organisms and cancer cells

selective toxicity

chemotherapy is based on this principle, wc is the property of substances of being more harmful to certain living organisms but not to others

• insecticides selectively harmful to insects etc

chemotheraphy

in popular usage, this term is usually assc w tx of cancer w drugs

chemotherapeutic agents

drugs used for chemotherapy are generally called?

• classified accdg to the type of organisms against wc they act

antimicrobial

is a natural or synthetic drug that acts against one or more types of microorganisms

antibiotic

refers strictly to a substance produced by various spp of microorganisms wc inhibits the growth of another microorganism

host (patient), pathogen (disease-causing microorganism), drug (chemotherapeutic agent)

chemotherapeutic triad

the drug acts on pathogen

chemotherapeutic triad:

resulting in eradication of the pathogen or inhibition of its growth

• prolonged exposure to less than therapeutic concentrations of drug exerts a selective pressure on the pathogen enabling it to devise ways to develop resistance

the pathogen acts on drug

chemotherapeutic triad:

resulting in inactivation of drug or resistance to drug effect

the drug acts on host

chemotherapeutic triad:

resulting in toxicity, allergy, biological alteration, or immunosuppression

the host acts on drug

chemotherapeutic triad:

resulting in drug excretion and/or biotransformation

the pathogen acts on host

chemotherapeutic triad:

resulting in stimulation or weakening of the immune response and dss

the host acts on pathogen

chemotherapeutic triad:

resulting in immune defense mechanisms resolving the dss

minimum inhibitory concentration

the lowest dilution of drug that prevents visible growth in broth or agar after 18-24 hrs of incubation

minimum bacteriocidal concentration

the lowest concentration or dilution of drugs that sterilizes the medium or results in a 99.9% decline in bacterial count

post-antibiotic effect

inhibition of growth after the antibiotic level falls off below the minimum inhibitory concentration

• may not be observed w all antibiotics

bacteriocidal

the drug is capable of killing bacterial organisms at a clinically achievable concentrations

bacteriostatic

the drug, at clinically achievable concentration, inhibits bacterial growth but does not kill the organisms

• when the drug is removed, bacterial growth may resume

bacteriolytic

cause dissolution of bacterial cells

penicillins, cephalosporins, bacitracin, vancomycin

inhibitors of cell wall synthesis

polymixins

disruptors of cell membrane

aminoglycosides, tetracyclines, macrolides, lincosamides, chloramphenicol, tiamulin, virginiamycin

inhibitors of protein synthesis (atm lc tia-v)

quinolones, fluoroquinolones, novobiocin, metronidazole, nitrofurans, rifamycins

inhibitors of nucleic acid fx (qfq nom nf r)

sulfonamides, trimethoprim

inhibitors of folate cofactor synthesis

gram positive cocci and bacilli

accdg to spectrum of antibacterial action:

natural penicillins (pen g, pen v)

gram positive cocci and bacilli

accdg to spectrum of antibacterial action:

semi-synthetic penicillins (oxacillin, nafcillin)

gram positive cocci and bacilli

accdg to spectrum of antibacterial action:

macrolides (erythromycin, tylosin, spiramycin)

gram positive cocci and bacilli

accdg to spectrum of antibacterial action:

lincosamides (lincomycin, clindamycin)

gram positive cocci and bacilli

accdg to spectrum of antibacterial action:

vancomycin and bacitracin

aerobic gram negative bacilli

accdg to spectrum of antibacterial action:

aminoglycosides (streptomycin, gentamicin, neomycin)

aerobic gram negative bacilli

accdg to spectrum of antibacterial action:

polymyxins (polymixin b, colistin)

broad spectrum (gram positive and negative bacilli)

accdg to spectrum of antibacterial action:

broad spectrum penicillins (ampicillin, amoxicillin, carbenicillin, piperacillin)

broad spectrum (gram positive and negative bacilli)

accdg to spectrum of antibacterial action:

cephalosporins

broad spectrum (gram positive and negative bacilli)

accdg to spectrum of antibacterial action:

trimethoprim-sulfonamide combinations

broad spectrum (gram positive and negative bacilli)

accdg to spectrum of antibacterial action:

tetracycline (chlortetracycline, oxytetracycline, doxycycline)

broad spectrum (gram positive and negative bacilli)

accdg to spectrum of antibacterial action:

fluorquinolones (norfloxacin, ciprofloxacin enrofloxacin, danofloxacin)

true

TRUE OR FALSE: penicillins and cephalosporins by virtue of their action require active multiplication of bacteria to be effective

bacteriocidal agents

agents that are more prone to causing superinfection bc they may kill off normal bacterial flora, wc normally inhibits pathogens

bacteriostatic agents

agents that may antagonize the action of the same agent

true

TRUE OR FALSE: some bacteriostatic drugs may become bacteriocidal when very high doses are given or when high concentrations are attained in certain body compartment such as the urinary tract

true

TRUE OR FALSE: when using bacteriostatic drugs, the normal defense mechanism of the px must participate in eliminating infectious bacteria

inhibitors of cell wall synthesis

• Usually bacteriocidal and require active bacterial multiplication to be effective because new cell wall is produced during rapid bacterial cell multiplication

• Indicated for conditions when the host's defense mechanisms are depressed

• Have a greater tendency to induce superinfection

• Simultaneous use of bacteriostatic agents may antagonize the effect of this group

disruptors of cell membrane

• Generally bacteriocidal

• Their action is not dependent on the rate of active bacterial growth or multiplication, and therefore, may be combined with bacteriostatic agents

inhibitors of protein synthesis

• May be either bacteriocidal (aminoglycosides) or bacteriostatic

• Their action is not dependent on the rate of bacterial multiplication

inhibitors of nucleic acid functions

inhibit the metabolism and fx of either rna or dna

• usually bacteriocidal

inhibitors of folate cofactor synthesis

they are generally bacteriostatic but fixed combinations of trimethoprim and sulfonamides are bacteriocidal

mutation, transduction, transformation, conjugation

ways of acquiring bacterial resistance to antibiotics

mutation

when the use of a particular drug is widespread, the sensitive strains are suppressed, and the resistant ones multiply unimpaired; in time the resistant strains predominate

transduction

occurs when a bacteriophage carries genetic materials for antibiotic resistance in a newly infected bacterial cell

• impt in the transfer of antibacterial resistance among strains of staph aureus, where bacteriophages carry plasmids

transformation

involves the incorporation into bacteria of dna that is contained in the environment

conjugation

refers to the passage of resistance genes from cell to cell by direct contact thru sex pilus

r-factor, resistance transfer factor

in conjugation, dna is transferred contained in plasmids and consists of 2 parts. what are these?

r-factor

the 1st part in conjugation wc codes for resistance

• resistance to multiple antibiotics

resistance transfer factor

the 2nd code in conjugation wc codes for the transfer apparatus

no effect, superinfection, induction of bacterial resistance, toxic effects, allergy, drug residues

when an antimicrobial drug is used to treat bacterial infections in animal patients, several possible outcomes of therapy may be expected; only one of which is beneficial. these are:

infection should specifically be diagnosed, appropriate dose must be given, dose schedule must be followed, drug must be available at the site of infection in a concentration above MIC

general principles of antibacterial therapy

microorganisms involved in infection, result of sensitivity test, pathogenicity, pharmacokinetics, potential drug toxicity, drug interactions

in selecting appropriate antibacterial drugs, it is best to consider the following:

antibiotic sensitivity tests

tests used to provide a sound foundation from wc to proceed w the selection of appropriate antibacterial drugs