ch 12: drugs, microbes, host-- chemotherapy

antimicrobial chemotherapy

the use of chemicals in therapy; includes antimicrobial treatment

goals of antimicrobial chemo

• Administer to infected person a drug that destroys infection
  without harming host. Drug should:

• Be easily administered

• Reach infection anywhere in the body

• Be able to kill the infectious agent, not just inhibit growth

• Remain active in body as long as needed

• Be safely and easily broken down and excreted

antibiotics

substance produced by natural metabolic process of microorganism (inhibit or destroy)

what are antibotics made from

spore-forming bacteria and fungi (most from bacteria)

semisynthetics

chemically altered antibiotics (more effective, easy to administer)

synthetics

antimicrobials that are completely synthesized in a lab

chemotherapeutic drug

any chemical ued in the treatment, releif, or prophylaxis of a disesse

antimicrobials (FINISH THE TABLE)

all-incusive term for any antimicrobial drug, regardless of its origin

5 Ways drugs slow/stop cell growth

1. Inhibition of cell wall synthesis
2. Breakdown of the cell membrane structure or function
3. Interference with function of RNA or DNA
4. Inhibition of protein synthesis, and
5. Blockage of key metabolic pathways

selectively toxic

can kill or inhibit microbes without simutaneously damaging the host

Narrow Spectrum (llimited spectrum)

antimicrobials effective against a limited array of microbial types; for example, a drug effective mainly on gram-positive bacteria

broad spectrum (extended spectrum)

effective against many organisms
- may allow for secondary or superinfections to develop

- killing of normal flora reduces microbial antagonism

(normal microbiota versus secondary infection by opportunistic pathogens)
- when one part of a balanced flora is killed off, a pathogen has the opportunity to take over

prophylaxis

antimicrobial chemotherapy

combined therapy (combination)

synergy (synergestic effect)

inhibition of cell wall synthesis

• Prevent bacteria from increasing amount of peptidoglycan

•  Have no effect on existing peptidoglycan layer

•  Effective only for growing cells

Why do inhibitor of cell wall synthesis only like Beta lactum drugs are only usegul on growing cells

inhibition of protein synthesis

• Interference with prokaryotic ribosomes

• Prokaryotic ribosomes are 70S (30S and 50S)

• Eukaryotic ribosomes are 80S (40S and 60S)

• Drugs can selectively target translation

disruption of cytoplasmic membranes

some drugs from channels through cytoplasmic membrane and damage its intergrity

Antimetaboilc agent

*must have slective toxicity; can be effective when pathogen and host metabolic process differ

inhinition of nucleic acid synthesis

• Several drugs block DNA replication or RNA
  transcription

• Drugs often affect both eukaryotic and
  prokaryotic cells
  

• Not normally used to treat infections
  

• Used in research and perhaps to slow cancer
  cell replication

Ideal antimicrobial agents are

• Readily available

• inexpensive

• Chemically stable

• Easily administered

• Nontoxic and nonallergenic

• Selectively toxic against wide range of
  pathogens

pennicilin

from fungus

kirby bauer

different drugs have different diffusion rates (do not assume largest zone= most effective)

routes of administration of drugs

topical, oral, intramuscular, intraveneous

safety and side effects of antimicrobial drugs

TOXIC

• Cause of many adverse reactions poorly
  understood

• Drugs may be toxic to kidneys, liver, or nerves

• Consideration needed when prescribing drugs to
  pregnant women

therapeautic index (TI)

the ratio of the dose of a drug that can be tolerated to the drug’s effective dose

the development of resistance in populations

resistant in 2 ways:
1) new mutations of chromosomal genes (uncomon)
2) acquistion of R plasmids via transformation, transduction, and conjugation

mechanisms of resistance (7)

1.Produce enzyme that destroys or deactivates drug
2. Slow or prevent entry of drug into the cell
3. Alter target of drug so it binds less effectively
4. Alter their own metabolic chemistry
5. Pump antimicrobial drug out of the cell before it can act
6. Bacteria in biofilms can resist antimicrobials
7. Mycobacterium tuberculosis produces MfpA protein
-  Binds DNA gyrase, preventing the binding of
fluoroquinolone drugs

multiple resistance

are resistant to at least three antimicrobial agents

cross resistenace

can occur when drugs are similar in structure

retarding resistance

maintain high conentration of drug in patient for sufficient time (inhibit pathogen so immune system can eliminate)

synergism (use antimicrobal agents in combination)

occurs when one drug enhances the effect of a second drug

antagonism (use antimicrobial agents in combination)

occurs when drugs interfere with each other