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63 Cards in this Set

  • Front
  • Back
What is the goal of antimicrobial chemotherapy?
to administer drug to infected person that can destroy the infectious agent and leave the host cells alone
What must a drug be?
be easy to administer; able to reach the infectious agent in the body; be toxic to infectious agent and nontoxic to host; remain in the body as long as needed, yet be safely and easily broken down and excreted (-sidal)
What is a chemotherapeutic drug?
any chemical used in the treatment, relief, or prophylaxis of a disease
What is prophylaxis?
use of a drug to prevent imminent infection of a person at risk
What is antimicrobial chemotherapy?
the use of chemotherapeutic drgus to control infection
What are antimicrobials?
an all-inclusive term for any antimicrobial drig, regardless of its origin
What are antibiotics?
substances produced by the natural metabolic processes of some microorganisms that can inhibit or destroy other microorganisms
What are semisynthetic drugs?
drugs that are chemically modified in the laboratory after being isolated from natural sources
What are synthetic drugs?
drugs produced entirely by chemical reactions
What are narrow spectrum drugs?
limited spectrum drugs; antimicrobials effective against a limited array of microbial types; Ex. a drug effective mainly on gram-positive bacteria
What are broad spectrum drugs?
extended spectrum; antimicrobials effective against an wide variety of microbial types; Ex. A drug effective against both gram+ and gram- bacteria
What are antibiotics common metabolic products of?
aerobic bacteria and fungi
What are antibiotics produced to do?
inhibit the growth of competing organisms
What are antibiotics derived from?
Bacteria in the genera Streptomyces and Bacillus; Molds in the genera Penicillum and Cephalosporium
What do we need to know before we treat a patient?
nature of the organism(s) you are fighting that is causing the infection; drug sensitivity of agent; patient history (liver and kidney)
How do doctors identify the agent?
identify from patient specimens- doctors use test data or an informed guess
Why is it necessary for testing for drug sensitivity/ susceptibility?
necessary for bacteria commonly showing resistance
What is it difficult and unnecessary for?
fungal or protozoan infections
What is a technique used for testing drug susceptibility? Describe
kirby bauer; agar plate is spread bacteria, small discs containing prepared amount of antibiotic are placed on the plate, zone of inhibition- measure
What is an antibiogram?
it provides data for drug selection
What is kirby bauer not ideal for?
anaerobes, fastidious (finicky) bacteria, slow growing bacteria
What is another test that more sensitive and accurate?
tube dilution tests
What do you do for this test?
antimicrobial is diluted serially in tubes of broth; each tube is inoculated with uniform sample of pure culture
What is MIC?
minimum inhibitory concentration: the smallest concentration of drug that visibly inhibits growth
What is MIC useful for?
determining the effective dose
What is treatment failure due to?
in vitro (outside body): activity of drug not always correlated with the in vivo effect (inside body)
What is failure of antimicrobial treatment due to?
drug can't diffuse to body compartment; resistant microbes not collected for testing; mixed infection
What is the therapeutic index?
the ratio of the toxic dose compared to its minimum effective (therapeutic) dose
What is a better therapeutic index?
the smaller the ratio the greater the potential for drug reactions
1.1 is risky
10 is safer
-the drug with the highest therapeutic index has the widest margin of safety
=toxic does/therapeutic dose
How do you decide on a course of treatment?
physician must take a careful history before prescribing antibiotic: patient history, age, other drugs patient is taking, how medication can be taken, cost
What are the goals of antimicrobial drugs?
to disrupt cell processes of bacteria, fungi or protozoa; inhibit virus replication; interfere with the function of enzymes required to synthesize or assemble macromolecules; destroy structures already formed in the cell
What is a selectively toxic drug?
it can kill/ inhibit the actions or synthesis of molecules in microorganisms but not in vertebrate cells (host cells)
What do drugs with excellent selective toxicity do?
block the synthesis of the bacterial cell wall
What drugs are most toxic to humans?
drugs that act upon a structure common to both the infective agent and the host cell
-common with microbe cells: DNA cells membrane- could potentially affect us
What are the antimicrobial drug categories?
-inhibit cell wall synthesis; inhibition of nucleic acid structure and function; inhibition of protein synthesis; interference with cell membrane structure and function; inhibition of folic acid (puts together a nucleic acid) synthesis
Broad spectrum vs narrow spectrum drugs
effective against a large number of bacterial types;
target a specific group
Why do eukaryotic cells present special problems in chemotherapy?
only a few agents with special antifungal properties have been developed
What agents are used to treat fungal infections?
Macrolide polyenes: attach fungal membranes
Azoles: sterile sunthesis
Echinocandins: cell wall synthesis
Nucleotide cytosine analog: DNA/RNA
-more similar a microbe is to us, the harder it is to kill it
What antimalarial (antiparasitic) drug is used?
Quinine
has been replaced by synthesized quinolones, chloroquine and primaquine
malaria is caused by genus plasmodium
What chemotherapy for other protozoan infections is used?
Metronidazole; it is widely used amoebicide (eukaryotic=similar to humans)
-treats intestinal infections and hepatic disease caused by Entamoeba hystolytica
What are the challenges of antihelminthic drug therapy?
flukes, tapeworms, round worms, larger parasites; their physiology is much more similar to humans; blocking reproduction does not affect adult worms; most effective drugs kill/destroy all stages of the life cycle
What are unique challenges in the chemotherapeutic treatment of viruses?
viruses rely on a host cell for most metabolic functions; disrupting viral metabolism requires disruption of our own cell metabolism and processes; measles, mumps, and hepatitis are prevented through the use of vaccines
What are the major modes of action of antiviral agents?
block penetration of the virus into the host cell; blocking transcription and translation of viral molecules; preventing maturation of viral particles
What is drug resistance?
An adaptive response- microorganisms tolerate a drug that would normally be inhibitory
What is drug resistance due to?
it is due to the genetic versatility and adaptibility of microbial populations
-transformation, transduction, conjugation
-phenotypic change
How does drug resistance develop?
microbes become newly resistant to a drug after one of the following occurs: spontaneous mutations in critical genes; acquisition of entire new gene or set of genes via horizontal transfer from another species
What are resistance factors?
plasmids (small circular part of DNA) containing antibiotic resistance genes
How can resistance factors be transferred?
through conjugation, transformation or transduction; transposons- "jumping genes"
What are the 5 mechanisms of drug resistance?
new enzymes inactivates drug; permeability of drug is decreased; drug is immediately eliminated; drug binding sites changes; an affected metabolic pathway is shut down or an alternative is used
What are the long-term therapeutic consequences?
population-one is resistant
bacteria in an infection-take all antibiotics prescribed: kills vulnerable cells, non resistant cells; makes a resistant population
What are the events in natural selection for drug resistance?
sensitive cells die, resistance mutant cells survive and all cells are now resistant
What are the 4 new approaches to antimicrobial therapy?
1. targeting iron-scavenging capabilities of bacteria
2. using RNA interference strategies- to shut down metabolism of pathogenic microbes
3. mimicking defense peptide molecules- peptides of 20-50 amino acids, part of the mammalian innate immune system called defensin, magainins, and protegrins
4. using bacteriophages: they are specific-infect only one species of bacterium
What are probiotics?
can replace microbes lost during antimicrobial therapy
What are prebiotics?
nutrients that encourage the growth of beneficial microbes
What are side effects of drugs?
-direct damage to tissues
-allergic reactions
-disruption to normal biota
What organs can drugs adversely affect?
liver, kidneys, GI tract, cardiovascular system and blood forming tissue, nervous system, respiratory tract, skin, bones and teeth
What is an allergy?
an increased sensitivity to a drug
What does a drug act in a allergic response?
drugs act as an antigen that stimulates the allergic response
When does sensitization occur?
during the second exposure it can lead to hives, respiratory inflammation or anaphylaxis
What is biota?
normal microbial colonists of healthy body surfaces
What antimicrobials can destroy healthy biota?
broad spectrum- this can lead to a superinfection
What is a superinfection?
microbes that were once small in number overgrow when normal resident biota are destroyed by broad-spectrum antimicrobials
What is the role of antimicrobials in disrupting microbial biota and causing superinfections?
Normal biota important to maintain intestinal balance; drug destroys beneficial biota; pathogen overgrows