November 4 Flashcards
(25 cards)
Sulfanilamide
1932
First antimicrobial chemical used to treat a wide range of microbes
Streptomyces
More than 1/2 of antibiotics are derived from Streptomyces bacterium in soil, usually semisynthetics
Semisynthetics
Altering naturally produced antibiotics in a lab to make them more readily absorbed, more resistant to low pH
Synthetics
Synthesized in a lab
Seletive Toxicity
You want the drug to be more toxic to the pathogen than to the host, so you target diffrences between the host and pathogen (cell walls). There are more antibacterial drugs than anything else (largest in number and diversity), there are fewer drugs to treat eukaryotic infections (antiprotozoal drugs, antifungals), the fewest number and diversity is in antiviral drugs, viruses use a lot of the host cell’s enzymes to metabolize and replicate making it difficult to selectively target viruses.
Mechanisms of Antimicrobial Action
1) Inhibition of cell wall synthesis
2) Inhibition of protein synthesis
3) Disuption of cytoplasmic membrane
4) Inhibition of Metabolic Pathways
5) Prevention of Viral Attachment
Inhibition of Cell Wall Synthesis
Damages the cell wall, leaving the cell with no protection from osmotic pressure, the cell will lyse.
This is a good target, human cells lack cell walls
Many act on growing cells (log stage), peptidoglycan is actively growing.
How do B-lactams work?
Prevent the formation of amino acid crossbridges between NAM units, they do not affect peptidoglycan that has already been made. Many drugs are semisynthetic derivatives of b-lactams (more stable in acidic environments, more readily absorbed, more active against more types of bacteria).
The simplest b-lactams are only effective against aerobic Gram-negative bacteria.
Examples: Cephalosporins and Penicillin
B-lactamase Sensitivity
B-lactamase breaks down b-lactams
Many microbes naturally produce b-lactamase, but there are some semisynthetics that can inhibit B-lactamase.
Vancomycin
Interferes with specific alanine-alanine crossbridges in many Gram-positive bacteria
(Cell wall inhibition)
Bactrim
Blocks secretion of NAG and NAM from the cytoplasm, selectively toxic because it has no effect on animal cells (no cell wall) or plant cells (no peptidoglycan)
(cell wall synthesis inhibition)
Inhibition of Protein Synthesis
Proteins: enzymes, structural, regulation, pumps, channels-transport across membranes
Selectively toxic: Prokaryotic ribosomes are 70S, composed of 30S subunit and 50S subunits, but Eukaryotic ribosomes are 80S and composed of 60S and 40S subunits.
Mitochondial and chloroplast ribosomes however, are 70S, made of 30S and 50S
Single subunits can be targeted
30S Inhibitors
Tetracycline
Streptomycin
50S Inhibitors
Arthromycin
Chloramphenicol
Narrow Spectrum
Treats only a few specific pathogens
Broad Spectrum
Treats a variety of pathogens, this can be problematic you can kill the host’s natural microflora, such as in the gut and vagina.
Why are broad spectrum antibioitics a problem?
They can kill the host’s natural microflora causing secondary infections such as: Clostridium difficile causes psuedomembranous colitis (C. diff), Candida albicans causes yeast infections
Disruption of the Cytoplasmic membrane
Many drugs become incorporated into the membrane and damage its integrity, usually by forming pores.
Examples: Polymixons, Amphotericin
Polymixons
Disrupts the cell membrane of some Gram-negative bacteria, but it is highly toxic to human kidneys
Amphotericin B
Targets ergosterol in the cell membrane of fungi (ergosterol is similar to cholesterol), it forms pores in the cell membrane. Humans can be somewhat susceptible , there are a lot of toxicity issues with oral antifungals–the liver and kidneys must be carefully monitored.
Inhibition of Metabolic Pathways
Must be careful to NOT shutdown the host
Antimetabolic agents are commonly heavy metals such as arsenic. Some arsenic drugs treats sleeping sickness caused by a protozoan.
Antihelmanthic Drugs
Used in the treatment of parasitic worms that stay in place by swimming in the intestines. These drugs paralyze the worm and it exits in the feces.
Example: Human Round Worm, *Ascans lumbricoides *
Praziquantal
Prevention of Viral Attachment
To invade the host cell, viruses must attach to the host cell via chemical attachment
Attachment proteins on viruses and complementary receptor protein on host cell
Attachment antagonists–peptide and sugar analogs of proteins
Prokaryotic Ribosome Structure
70S
Made up of 30S and 50S
