chp.9 antimicrobial chemotherapy

Question 1

Define antibiotic

Answer 1

microbial products or their derivatives that kill susceptible microbes or inhibit their growth

Question 2

Which was the first true antibiotic? Who was it discovered by and how?

Answer 2

Penicillin.Accidentally discovered by Alexander Fleming (1928): observed penicillin activity on contaminated plate, did not think could be developed further

Question 3

an antibiotic active against tuberculosis discovered by

Answer 3

Streptomycin, Selman Waksman in 1944

Question 4

were all isolated from Streptomyces species

Answer 4

Chloramphenicol, terramycin, neomycin, and tetracycline

Question 5

What is Paul Ehrlich known for?

Answer 5

1904: developed concept of selective toxicity, identified dyes that effectively treated African sleeping sickness

Question 6

What is Sahachiro Hata known for?

Answer 6

1910: working with Ehrlich, identified arsenic compounds that effectively treated syphilis, Salvarsan against Treponema pallidum

Question 7

What are Gerhard Domagk and Jacques and Therese Trefouel known for?

Answer 7

1935: discovered sulfonamides and sulfa drugs, Prontosil

Question 8

Define selective toxicity:

Answer 8

chemotherapeutic agents

Question 9

Define the therapeutic index:

Answer 9

the ratio of the toxic dose to the therapeutic dose, larger the index, better the drug, for drugs that disrupt structure or function not found on host, such as peptidoglycan

Question 10

How is the effectiveness of antimicrobial drugs expressed?

Answer 10

minimal inhibitory concentration (MIC): lowest concentration of drug that inhibits growth of pathogen, minimal lethal concentration (MLC): lowest concentration of drug that kills pathogen

Question 11

How is the level of antimicrobial activity tested?

Answer 11

dilution susceptibility tests for MIC, disk diffusion test (Kirby Bauer),the Etest

Question 12

What are the main modes of action by antimicrobial drugs? List examples of each and how they work.

Answer 12

Inhibitors of cell wall synthesis, Protein synthesis inhibitors: Many antibiotics bind specifically to the bacterial ribosome, binding can be to 30S or 50S ribosomal subunit, Other antibiotics inhibit a step in protein synthesis: a) aminoacyl-tRNA binding, b) peptide bond formation, c) mRNA reading, d) translocation
Metabolic antagonists: Act as antimetabolites  antagonize or block functioning of metabolic pathways by competitively inhibiting the use of metabolites by key enzymes, Are structural analogs molecules that are structurally similar to, and compete with, naturally occurring metabolic intermediates, block normal cellular metabolism, Broad spectrum, but bacteriostatic
Nucleic acid synthesis inhibition: A variety of mechanisms: block DNA replication, inhibition of DNA polymerase, inhibition of DNA helicase, block transcription inhibition of RNA polymerase, Drugs not as selectively toxic as other antibiotics because bacteria and eukaryotes do not differ greatly in the way they synthesize nucleic acids

Question 13

Antiviral drugs are currently used to

Answer 13

drug development has been slow because it is difficult to specifically target viral replication

Question 14

What are the antiviral drugs used to treat influenza and how do they work?

Answer 14

Amantadine: used to prevent influenza infections, blocks penetration and uncoating of the influenza virus, A neuraminidase inhibitor: not a cure for influenza, but shortens course of illness, there are resistant viruses

Question 15

What are the antiviral drugs used to treat herpesvirus infections and how do they work?

Answer 15

Acyclovir: inhibits herpes virus DNA polymerase, Adenine arabinoside (vidarabine): inhibits herpes virus enzymes involved in DNA and RNA synthesis and function, Valacyclovir: prodrug form of acyclovir

Question 16

What are antiviral drugs used to treat HIV and how do they work?

Answer 16

1. Nucleoside reverse transcriptase inhibitors (NRTIs): produce faulty DNA, 2.Nonnucleoside reverse transcriptase inhibitors (NNRTIs): prevent HIV DNA synthesis, 3.Protease inhibitors (PIs): mimic peptide bond that is normally attacked by the protease, 4.Integrase inhibitors: prevent HIV genome incorporation, 5.Fusion inhibitors: prevent HIV entry into cells

Question 17

The most successful treatment method is:

Answer 17

drug cocktails to curtail resistance

Question 18

What is the process for treating Mycoses?

Answer 18

Main target: ergosterol, Superficial mycoses: Candida albicans, topical and oral, disrupt membrane permeability and inhibit sterol synthesis, disrupts mitotic spindle; may inhibit protein and DNA synthesis, Systemic mycoses: difficult to control and can be fatal, three common drugs: amphotericin B – binds sterols in membranes, highly toxic, 5-flucytosine – disrupts RNA function, fluconazole – low side effects, used prophylactically, HIV and immunocompromised patients

Question 19

List the antiprotozoan drugs mentioned and what they target:

Answer 19

chloroquine and mefloquine – Plasmodium, metronidazole – Entamoeba and Trichomonas infections, combination drug therapy – Toxoplasma gondii

Question 20

Explain why drug resistance is a problem when it comes to its effectiveness:

Answer 20

once resistance originates in a population it can be transmitted to other bacteria, a resistance mechanism is not confirmed to a single class of drugs

Question 21

How can we determine the effectiveness of a drug?

Answer 21

must understand how the drug arrives at the site of infection, make sure the pathogen is susceptible to the drug, drug levels should exceed the pathogen’s MIC

Question 22

How can we fight against drug resistance?

Answer 22

give drug in appropriate concentrations to destroy susceptible, give two or more drugs at same time, use drugs only when necessary