Lecture #10 Flashcards
What is the primary goal of antimicrobial chemotherapy?
Destroy infective agents without harming host cells.
What are the ideal characteristics of an antimicrobial drug?
- Toxic to microbes, not host cells
- Microbicidal, not microbistatic
- Soluble and effective in body fluids
- Long-lasting potency without premature breakdown
- Does not promote antimicrobial resistance
- Supports host defenses
- Remains active in tissues and body fluids
- Delivered effectively to infection site
- Avoids allergies or secondary infections to the host
Define narrow-spectrum antimicrobials.
Effective against specific microbes.
Define broad-spectrum antimicrobials.
Effective against a wide range of microbes.
What three factors should be considered before therapy begins?
- Identity of the microorganism
- Microorganism’s drug susceptibility
- Patient’s medical condition
What is the Kirby-Bauer Technique used for?
Measures zone of inhibition on agar plates.
What does the Tube Dilution Test determine?
Minimum Inhibitory Concentration (MIC).
What does the Therapeutic Index (TI) represent?
Ratio of toxic dose to therapeutic dose.
How is a higher Therapeutic Index (TI) interpreted?
Safer drug.
What preexisting conditions must be considered before prescribing an antibiotic?
- Preexisting conditions that might influence drug activity
- History of allergy to a certain class of drugs
- Underlying liver or kidney disease
- Special precautions for infants, the elderly, and pregnant women
- Intake of other drugs that can increase toxicity
What is the goal of antimicrobial drugs?
Selectively toxic: kill or inhibit microbial cells without damaging host tissues.
What are the categories of mechanisms of drug action?
- Inhibit cell wall synthesis
- Inhibit nucleic acid synthesis
- Inhibit protein synthesis
- Disrupt cytoplasmic membrane
- Inhibit folic acid synthesis
Name a drug that targets the cell wall.
- Penicillins
- Cephalosporins
- Carbapenems
What do aminoglycosides do?
Cause misreading of the mRNA.
What is the action of tetracyclines?
Block the attachment of tRNA on the A acceptor site.
What do macrolides inhibit?
Inhibit translocation of the subunit during translation.
What do fluoroquinolones target?
Inhibit DNA unwinding enzymes of helicases.
What do polymyxins interact with?
Membrane phospholipids; distort the cell surface.
What is a broad-spectrum antibiotic?
Effective against multiple bacterial groups.
What is a narrow-spectrum antibiotic?
Targets specific bacteria.
Name an agent used to treat fungal infections.
- Macrolide Polyenes: Amphotericin B
- Azoles: Ketoconazole, fluconazole, clotrimazole
- Echinocandins: Micafungin, caspofungin
- Allylamines: Terbinafine, naftifine
What is metronidazole used for?
Widely used amoebicide; also treats Giarda Lamblia and Trichomonas Vaginalis.
What is a significant challenge when treating viral infections?
Disrupting viral metabolism requires disruption of host cellular metabolism.
What are some agents that inhibit virus entry?
- Enfuvirtide
- Amantadine
What are the causes of antimicrobial resistance?
- Spontaneous mutations in critical chromosomal genes
- Horizontal gene transfer
- Slowing or stopping of metabolism
What are common mechanisms of drug resistance?
- Enzymes inactivate drugs
- Decreased drug uptake
- Drug elimination via pumps
- Altered drug binding sites
- Alternative metabolic pathways
What is the consequence of natural selection in microbial populations?
Drug-resistant populations have a selective advantage.
What is the urgent problem regarding antimicrobial resistance?
We may enter a postantibiotic era where some infections will be untreatable.
What is one new approach to antimicrobial therapy?
Using RNA interference strategies.
What are the adverse effects of antimicrobials?
- Toxicity affecting various systems
- Superinfections from resistant microbes
What is the issue with broad-spectrum antimicrobial therapy?
Leads to superinfections and other adverse reactions.
What is the safest antibiotic based on Therapeutic Index?
Drug B (TI = 12).
What is the least toxic mode of action for antibiotics?
Acts on peptidoglycan cell wall.