Micro test 3

• 1. Synthetic drugs: human made.
• 2. Antibiotics: produced by microorganisms to offer seletive survival advantage to the host organism (kill competitors)

• 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.

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.

• 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: _

• 1. Identify microbe
• 2. Isolate organsim
• 3. Sensitivity testing
• -disk diffusion method (Kirby-Baer test)
• - broth dilution

• 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.

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.

• Suboptimal levels of drugs:
• -allow for replication (mutations and genetic recombination)
• -selection pressure for resistance

• 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