Chemotheraputic agents
Drugs that act against diseases. Examples include insulin, anticancer drugs, and drugs for treating infection.
Antimicrobial agents
Drugs that treat against infection.
Paul Ehrlich
Gave rise to chemotherapy to describe the use of chemicals that would selectively kill pathogens while having little or no effect on a patient. He coined the term "Magic bullets" that would bind to receptors on germs to bring about their death while ignor
Semisynthetics
Chemically altered antibiotics. These antibiotics are generally more effective, longer lasting, or easier to administer than naturally occurring antibiotics.
Synthetics
Antimicrobials that are completely synthesized in a laboratory. Most antibiotics are either natural or semisynthetic.
Selective toxicity
An effective antimicrobial agent must be more toxic to a pathogen than to the pathogen's host.
Why is selective toxicity possible?
Due to the differences in structures between pathogenic bacteria and their eukaryotic hosts. Fewer antifungal, antiprotozoan, and anthelmintic drugs are available because they are eukaryotic.
6 Methods of Antimicrobial Action.
1. Drugs that inhibit cell wall synthesis.
2. Drugs that inhibit protein synthesis.
3. Drugs that disrupt the cytoplasmic membrane.
4. Drugs that inhibit general metabolic pathways not used by humans
5. Drugs that inhibit nucleic acid synthesis.
6. Drugs
Drugs that inhibit cell wall synthesis.
1. Penicillins
2. Cephalosporins
3. Vancomycin
4. Bacitracin
5. Isoniazid.
6. Ethambutol
7. Echinocandins (antifungal)
ONLY FUNCTION TO KILL A CELL WHEN THE CELL IS GROWING OR REPRODUCING. DORMANT CELLS UNAFFECTED.
Drugs that inhibit protein synthesis.
1. Aminoglycosides
2. Tetracyclines
3. Chloramphenicol
4. Macrolides
5. Antisense nucleic acids
Drugs that disrupt cytoplasmic membrane.
1. Polymixins
2. Polyenes (antifungal)
Drugs that inhibit metabolic pathways.
1. Sulfonamides
2. Trimethoprim
3. Dapsone
Drugs that inhibit DNA/RNA synthesis.
1. Actinomycin
2. Nucleotide analogs
3. Quinolones
4. Rifampin
Drugs that inhibit attachment or recognition of pathogen to host.
1. Arildone
2. Pleconaril
Beta-lactams
Antibacterial agents that prevent the cross-linkage of NAM subunits.
How do beta-lactams function?
It inhibits peptidoglycan formation by binding irreversibly to the enzymes that cross-link NAM subunits. As a result, growing bacterial cells have weakened cell walls that are less resistant to osmotic pressure. The cell then lyses and dies.
Examples of beta-lactams.
Penecillins, cephalosporins, carbapenems
Vancomycin and cycloserine
Disrupt cell wall formation. They directly interfere with alanine-alanine bridges that link the NAM subunits in G+ bacteria
Bacitracin
Blocks the transport of NAG and NAM from the cytoplasm out to the wall, which results in cell lysis due to the effects of osmotic pressure.
Genus Mycobacterium
(Leprosy and tuberculosis) Have unique cell walls that have a layer of arabinogalactan-mycolic acid in addition to having a peptidoglycan layer. Mycobacteria typically reproduce only every 12-24 hours, so drugs acting against mycobacteria must be administ
Drugs that disrupt the mycolic acid layer.
Isoniazid (INH) or Ethambutol.
Prokaryotic v. Eukaryotic ribosomes.
Prokaryotic: 70S ribosome composed of the 50S and 30S subunits.
Eukaryotics: 80S ribosome composed of the 60S and 40S subunits.
Eukaryotic mitochondria ribosome concerns.
Mitochondria of eukaryotes contain 70S prokaryotic ribosomes. Endosymbiotic theory.
Drugs that target the 30S ribosomal unit.
Aminoglycosides and tetracyclines.
Action of aminoglycosides
Aminoglycosides change the shape of the 30S subunit, which makes it impossible for the ribosome to read the codons of mRNA correctly.
Action of tetracyclines
Tetracycline blocks the tRNA docking site (A site) , which prevents the incorporation of additional amino acids into a growing polypeptide.
Drugs that target the 50S ribosomal unit
Chloramphenicol and macrolides.
Action of chloramphenicol.
Chloramphenicol binds to the enzymatic site of the 50S subunit, which prevents translation.
Action of macrolides.
Macrolides bind to a portion of the 50S, which prevents the movement of the ribosome from one codon to the next.
Action of antisense nucleic acid.
RNA or single-stranded DNA molecules are designed to specifically complement mRNA molecules of pathogens. They block ribosomal subunits from attaching to that mRNA
FOMIVIRSEN
Drugs that disrupt the cytoplasmic membrane
polyenes (antifungal)
azoles (antifungal)
polymixin
Action of polyenes
Polyenes attach to ergosterol, a constituent of fungal membranes and cause lysis of the cell. Human cells are somewhat susceptible to polyenes since ergosterol and cholesterol are similar in chemical structure.
AMPHOTERICIN B
Action of azoles
Azoles inhibit the synthesis of ergosterol. Without ergosterol the cytoplasmic membrane does not remain intact. Azoles are generally not harmful to humans since humans do not produce ergosterol.
Action of sulfanomides
Sulfanomides act as antimetabolic drugs because they are structural analogs of para-aminobenzoic acid (PABA), which is crucial in the synthesis of nucleotides required for DNA and RNA synthesis. Sulfanomides compete with PABA for the active site of the en
Action of trimethoprim
Trimethoprim interferes with nucleic acid synthesis. Trimethoprim binds to the enzyme in the second step of the metabolic pathway that involves PABA, which helps to produce THF (tetrahydrofolic acid- a form of folic acid that is used as a coenzyme in the
PABA
para-aminobenzoic acid, which is converted to dihydrofolic acid, which is converted to tetrahydrofolic acid.
THF
Tetrahydrofolic acid (THF) is a form of folic acid that is used in the synthesis of purine and pyrimidine nucleotides
Nucleotide Analogs
molecules with structural similarities to normal nucleotide building blocks of nucleic acids. AZT used in anti-AIDS drug.
Actinomycin
Binds directly to DNA and prevents DNA synthesis. Drugs like this are not used in clinical treatment but rather for research as a marker. However, they can be used to slow the growth rate of cancer cells.
Quinolones
Quinolones inhibit DNA gyrase, which is an enzyme necessary for correct coiling and uncoiling of replicating bacterial DNA. Have little effect on eukaryotes and viruses.
Reverse transcripticase inhibitors.
Part of the AIDS cocktail that are against reverse transcripticases, which is an enzyme HIV uses early in its replication cycle to make DNA copies of its RNA genome
Adrilone and pleconaril
Block attachment of viruses and deter infections.