Antimicrobial Drugs Flashcards
What similar problems are enountered w/ antiviral, antifungal, antiprotozoan, and antihelminthic drugs?
- At the cellular level, fungus, protozoan, or helminth resemble the human cell much more closely than a bacterial cell does.
- Viral infections are particularly difficult to treat b/c the pathogen is w/i the human host’s cells
What is the primary factor involved in the selective toxicity of antibacterial action in Gram (-) bacteria?
- The primary factor lies in the LPS outer layer of Gram (-) bacteria & the porins that form water-filled channels across this layer.
(2. Drugs that pass thr. the porin channels must be relatively SMALL and HYDROPHILIC. )
When the identity of the pathogen is not known, does a Broad-Spec. drug or Narrow-Spec. drug work better? What is the disadvantage/side-effect administrating such drug? Give an example
- A broad-spec. drug would have an advantage in treating a disease by saving valuable time
- Disadvantage:
a. Many normal microbiota of the host can also be destroyed
b. If some of the normal microbiota are not destroyed, while the pathogenic ones are, the normal microbiota can become opportunistic pathogens - Example: Candida albicans
List the 5 modes of action of antimicrobial drugs
- Inhibitors of Cell Wall Synthesis
- Inhibitors of Protein Synthesis
- Inhibitors of Nucleic Acid Synthesis
- Injuries to Plasma Membrane
- Inhibiting the Synthesis of Essential Metabolites
Inhibition of Cell Wall Synthesis:
a. Name the type of drug
b. How does inhibition work?
c. Any adverse effects on human?
a. Penicillin
b. Inhibit synthesis of intact Peptidoglycan; consequently, the cell wall is greatly weakened and the cell undergoes lysis
Inhibition of Cell Wall Synthesis:
a. List the drugs
b. How does inhibition work?
c. Any adverse effects on human?
a. Penicillins, Cephalosporins, Bacitracin, Vancomycin, etc
b. Penicillins inhibit synthesis of intact Peptidoglycan; consequently, the cell wall is greatly weakened and the cell undergoes lysis
Inhibition of Protein synthesis
a. List the drugs
b. What is the mechanism?
c. Any adverse effects on human?
a. Chloramphenicol, Erythromycin, Tetracyclines, Streptomycin
b. Pro. cells have 70S ribosomes (50S & 30S)
1. Antibiotics that target the 50S subunit:
- - Chloramphenicol: inhibits the formation of peptide bonds in the growing polypeptide chain
- - Erythromycin:
1. Antibiotics that target the 30S subunit:
- - Tetracyclines: interfere w/ the attachment of the rRNA carrying the AAs to the ribosome
c. Though Euk. cells have 80S ribosomes, mitochondria also contain 70S ribosomes. So antibiotics targeting pro. ribosomes will also target mitochondrial ribosomes.
Chloramphenicol
a. Mode of action
b. Mechanism
a. Inhibit protein synthesis
b. Binds to 50S portion and inhibits formation of peptide bond
Erythromycin
a. Mode of action
b. Mechanism
a. Inhibit protein synthesis
b. Binds to 50S portion and prevents translocation-movement of ribosome along mRNA
Tetracycline
a. Mode of action
b. Mechanism
a. Inhibit protein synthesis
b. Interfere w/ attachment of tRNA to mRNA-ribosome complex
Streptomycin
a. Mode of action
b. Mechanism
a. Inhibit protein synthesis
b. Changes shape of 30S portion, causes code on mRNA to be read incorrectly
Inhibition of Protein synthesis
a. List the drugs
b. What is the mechanism?
c. Any adverse effects on human?
a. Chloramphenicol, Erythromycin, Tetracyclines, Streptomycin (Gentamycin)
b. Pro. cells have 70S ribosomes (50S & 30S)
1. Antibiotics that target the 50S subunit:
- - Chloramphenicol: inhibits the formation of peptide bonds in the growing polypeptide chain
- - Erythromycin:
1. Antibiotics that target the 30S subunit:
- - Tetracyclines: interfere w/ the attachment of the rRNA carrying the AAs to the ribosome
c. Though Euk. cells have 80S ribosomes, mitochondria also contain 70S ribosomes. So antibiotics targeting pro. ribosomes will also target mitochondrial ribosomes.
Chloramphenicol
a. Mode of action
b. Mechanism
c. Any adverse effects on human
a. Inhibit protein synthesis
b. Binds to 50S portion and inhibits formation of peptide bond
c. Chloramphenicol can suppress bone marrow activity, thus, affecting the formation of blood cells
Injury to the Plasma Mem.
a. List the drugs
b. What is the mechanism?
c. Any adverse effects on human?
a. Polymyxin B, Amphotericin B, Miconazole, Ketoconazole
b. Causes diruption of the plasma mem. by attaching to the phospholipids of the mem.
c. Plasma mem. of animal cells contain sterols, and amphotericin B and ketoconazole can be toxic to the host
- - Bacterial plasma mem. generally lack sterols, so these antibiotics do not work on bacteria.
Amphotericin B
a. Mode of action
b. Mechanism
a. Injury to the Plasma mem (antifungal)
b. Combine with sterols in the fungal plasma mem. to disrupt the mem.
Streptomycin
a. Mode of action
b. Mechanism
c. Adverse effects on human
a. Inhibit protein synthesis
b. Changes shape of 30S portion, causes code on mRNA to be read incorrectly
c. Aminoglycosides: Affect hearing by causing permanent damage to the auditory nerve
Inhibition of Nucleic Acid synthesis
a. List the drugs
b. Any adverse effects on human?
a. Rifampin and the Quinolones
c. Since they interfere w/ mammalian DNA and RNA as well, these drugs have an extremely limited usefulness. They are more widely used in chemotherapy
Inhibition of Nucleic Acid synthesis
a. List the drugs
b. Any adverse effects on human?
a. Rifampin and the Quinolones
c. Since they interfere w/ mammalian DNA and RNA as well, these drugs have an extremely limited usefulness. They are more widely used in chemotherapy due to toxicity
Sulfanilamide
a. Mode of action
b. Mechanism
c. Any adverse effects on human?
a. Inhibit the synthesis of Folate
b. Normally, para-aminobenzoid acid (PABA) is a substrate for the enzyme catalyzing folate synthesis. With the presence of Sulfanilamide, it binds to the enzyme, instead of PABA, so the folate synthesis stops.
c. Since humans don’t produce folate from PABA, the drug doesn’t harm the host.
Vancomycin
- Very narrow spectrum
- Inhibit cell wall synthesis
- Last line of antibiotic defense for treatment of Staphylococcus aureus
Isoniazid (INH)
a. Antimicrobial drug against Mycobacterium tuberculosis
b. Inhibit the synthesis of mycolic acids, which are components of cell walls only of the mycobacteria.
Ethambutol
- Effective only against mycobacteria
2. Inhibit incorporation of mycolic acid into the cell wall
Pseudomonas infections
a. What drug to use
b.
a. Gentamicin, Polymyxin B
b. Pseudomonads are a major problem for persons suffering from cystic fibrosis
List the 4 mechanisms that bacteria become resistant to chemotherapeutic agents
- Destruction or inactivation of the drug (ex. by beta-lactamase_
- Prevention of penetration to the target site w/i the microbe (a frequent mechanism for tetracyline resistance)
- Alteration of the drug’s target sites (ex. a single AA change in the ribosome may be enough to make the microbe resistant fto certain macrolide antibiotics)
- Rapid efflux (ejection), which pumps the drug out of the cell before it can become effective
