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Types of antimicrobial drugs.
- 1. Synthetic drugs: human made.
- 2. Antibiotics: produced by microorganisms to offer seletive survival advantage to the host organism (kill competitors)
Criteria for determining if an antimicrobial drug is effective for use in humans?
- 1. Selective toxicity against microbes under treatment & not human host cells.
- 2. Do not cause hypersensitive reactions in most hosts.
- 3. Ease of delivery to target sites -soluble in body fluids & not rapidly broken down or excreted.
- 4. Microbes being treated should not readily develop resistance.
Why don't we want to use broad spectrum drugs to treat all diseases?
Broad spectrum (adv) quickly (disadv) kill a wide range of flora, including normal flora that keep pathogens or potential resistant ones in check.
vs. Narrow spectrum -kill specific groups of microbes.
Why choose a particular drug for treatment?
- 1. Type of microbe:
- -drugs show diff ability to penetrate diff bac.
- -different target enzymes in diff bac.
- -cell structures e.g. gram_+ve cell wall
- 2. Site of infection: drug accessibility
- 3. Resistance: _
How do you determine what drug a particular microbe is susceptible to? Tests for microbial susceptibility.
- 1. Identify microbe
- 2. Isolate organsim
- 3. Sensitivity testing
- -disk diffusion method (Kirby-Baer test)
- - broth dilution
What are the major targets of antimicrobial drugs.
- 1. Inhibition of cell wall synthesis
- - Human cells have no cell wall e.g.... penicillin, cephalosporin, bacitracin, vancomycin..
- Why is penicillin ineffective against gram-ve bac?
- -thin layr of peptidoglycan cell wall
- -outer lipid mem inhibits penetration of drug.
- 2. Inhibition of protein synthesis
- - Prokaryote ribosomes 70S (50S & 30S) while eukaryote ribosome 80s.
- -e.g. chloramphenicol, erythromycin, streptomycin, gentamycin & tetracyclines
- -Mitochondria ribosomes are also 70S so can be affected... toxicity.
- 3. Injury to the plasma membrane
- -most bac. & fungal mem, diff phospholipids from animal cells e.g. polymyxin B causes disruption of membrane, binding to phospholipids; particularly effective agianst gram-ves... Why?
- 4. Inhibition of enzymatic activity
- -competitive inhibitor of enzyme by resembling the normal substrate e.g. sulfanilamide (sulfa drug) resembles para-aminobenzoic acid which is substrate leading to the synthesis of folic acid in bac. Humans do not synth folic acid but obtain it from food.
-Inhibition of nucleic acid synthesis, diffs in enzymes for nucleic acid synthesis e.g. quinolones interfere with bac dna gyrase needed for replication fork progression e.g. acyclovis inhibition of herpes virus specific DNA polymerase.
How do microorganisms become resistant to a particular drug?
1. Destruction: acquire enzyme that degrade drugs - resistance factors on plasmids, transduction etc..
2. Uptake reduction: decrease uptake of drug, mutation that results in reduced affinity of receptors for drug transport.
3. Target change: increased synthesis of affected target enzyme. mutation in target enzyme structure. resistance mutants will repl susceptible population.
What conditions encourage the appearance drug resistant organsims?
- Suboptimal levels of drugs:
- -allow for replication (mutations and genetic recombination)
- -selection pressure for resistance
How can we reduce microbial resistance to drugs?
- 1. Correct dosage & on time.... finish the rx!
- -maintenance of concentration to kill all quickly before chance of mutants generate.
- 2. Multiple drug therapy
- -reduce probabilty of development of resistance to multiple drugs