Chapter 9

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The activity of effective antiprotozoal drugs is centered largely on the suppression of metabolic activity in these cells. What conclusions can be drawn from this knowledge?

Selective toxicity will be low since protozoans have many metabolic processes in common with human host cells.

Select the antifungal drug mechanisms of action from the choices below.

Sterol synthesis inhibition, Disrupt mitotic spindle

Which of the following is normally treated by antifungal creams and solutions?

Superficial mycoses

Consider an antibacterial drug. In which of the following cases would the action of the drug be considered primarily bacteriostatic?

The MLC is 10-20 times higher than the MIC.

A young man arrives at the hospital with a Staphylococcus infection. A microbiologist at the hospital runs a disk diffusion test and obtains a zone diameter of 17 mm for clindamycin. The zone diameter interpretive standards for this drug-microbe combination are listed as: Resistant = <15, Intermediate = 15-20, Susceptible = >20. How should the results of this disk diffusion test be interpreted?

The Staphylococcus shows some susceptibility to the antibiotic clindamycin. It would not be recommended to use this antibiotic for this infection.

Sulfonamides inhibit an enzyme necessary for production of purines and pyrimidines. What long-term impact would it have on a microbe if it were grown in the presence of sulfonamides?

The cell would cease to divide.

If a new antifungal drug was discovered that had low selective toxicity and a high therapeutic index, what assumptions could be made about the drug?

The drug targets an essential molecule in fungi that is not present in a human cell.

Why are there far fewer antiviral agents than there are antibacterial agents?

Viruses enter host cells and make use of host components

Which of the following is the major reason why it has been difficult to treat viral infections with chemotherapeutic agents?

Viruses use the metabolic machinery of their hosts, which limits many of the potential points of attack.

Whose discovery of streptomycin stimulated an intense search for other antibiotics?

Waksman

The antibacterial drug mechanism of action that would have the highest therapeutic index is _________.

a drug that targets peptidoglycan cross-linking

The E test is _________.

a quantitative antibiotic sensitivity test that utilizes plastic strips impregnated with an antibiotic of interest

The concentration of an antimicrobial drug that is reached in the body will depend on _________.

all of the choices are correct

Which of the following affects the size of the clear zone in a disk diffusion test of antimicrobial susceptibility?

all of the choices are correct

Which of the following is (are) true about cephalosporins?

all of the choices are correct

Which of the following is (are) used by microorganisms to become resistant to a particular drug?

all of the choices are correct

Which of the following is a desirable general characteristic of antimicrobial drugs?

all of the choices are correct

Which of the following is a useful mechanism of action for an antibacterial drug?

all of the choices are correct

Chemotherapeutic agents that are natural products of microorganisms are most specifically referred to as __________.

antibiotics

The class of antimicrobials that would have the most selective toxicity is _________.

antimicrobials that inhibit cell wall synthesis

The most selective antibacterial agents are those that interfere with bacterial cell wall synthesis. This is because _________.

bacterial cell walls have a unique structure not found in eukaryotic host cells

A bacterial culture is growing as illustrated graphically. At the time indicated by the arrow labeled 1, an antibiotic is applied. At the time indicated by the arrow labeled 2, the culture medium is changed so that there is no antibiotic present. Match each growth pattern with the identification of the antibiotic as bacteriostatic or bactericidal.

bacteriostatic bacterialcidal

A key feature of penicillin is the _________ ring.

beta-lactam

Aminoglycoside antibiotics _________.

bind to 30s ribosomal subunit

Most antiprotozoal drugs target _________.

biosynthetic pathways

Penicillins are a group of antibiotics known for inhibiting ________ synthesis in _______.

cell wall, bacteria

Because of widespread resistance to penicillin, structurally related classes of antibiotics, the _______, were developed.

cephalosporins

Drugs used to treat malaria include _________.

chloroquine and qualaquin

Chemotherapeutic agents have different levels of activity and effectiveness, with some being __________ or strong enough to kill microbes while others are only ______, inhibiting microbial growth.

cidal, static

The mechanism of this type of antibiotic is to block the formation of _________ in the complex polymer __________.

cross-links, peptidoglycan

The most effective method by which antibiotic resistance can be decreased in bacteria is _________.

decrease in antibiotic use

The are several ways to measure these concentrations, including ______ tests where a series of drug concentrations is tested.

dilution susceptibility

Another important method is the _____ assay, where a ring of inhibition is seen around a piece of filter paper containing the antibiotic. The ____ method is the most common assay of this type.

disk diffusion, Kirby-Bauer

Since exposure to antibiotics is a selective force for maintaining resistance genes in a population, increasing antibiotic use will reduce overall resistance.

false

The antimicrobial action of artemisinin is not well understood but this chemical appears to _________.

form reactive oxygen intermediates inside Plasmodium-infected red blood cells

The chemotherapeutic agent must reach levels in the body that are ________ the pathogen's MIC value if it is going to be effective.

greater than

Sulfonamides and other drugs that inhibit folic acid synthesis have a high therapeutic index because _________.

humans do not synthesize folic acid but obtain it in their diets

Vancomycin _________.

inhibits the transpeptidation reaction in peptidoglycan biosynthesis

Assess the following statements and classify them according to whether they refer to inherent or acquired drug resistance.

intrinsic- hydrophobic outer membrane prevents intake of penicillin, bacterial cell wall lacks peptidoglycan so penicillin is ineffective acquired- genes code for drug-degrading enzymes, genes code for a membrane protein efflux pump, mutation in rRNA gene alters ribosome structure, drug targeted metabolic pathway is bypassed by alternate proteins

Isoniazid is a narrow-spectrum antibiotic that _________.

is one of the few drugs effective against Mycobacterium tuberculosis

The major reason why there are fewer antiprotozoal drugs than antibacterial drugs is because _________.

it is much more difficult to develop selectively toxic antiprotozoal drugs since protozoan cells are eukaryotic

The minimal lethal concentration (MLC) is the _________.

lowest concentration of a drug that kills a particular pathogen

The lowest concentration of an antibiotic that prevents growth is the _________.

minimal inhibitory concentration (MIC)

The lowest concentration that prevents microbial growth is the _______ concentration, while the lowest level that can kill microbes is the ________ concentration.

minimal inhibitory, minimal lethal

Which of the following does not inhibit protein synthesis?

penicillin

This is also its weak point, as penicillin-resistant pathogens contain the enzyme _____________ that destroys this ring.

penicillinase

All of the following are appropriate strategies for overcoming drug resistance in bacteria except _________.

prudent use of antibiotics when treating viral infections

Sulfonamides inhibit the production of folic acid and, therefore, inhibit the synthesis of __________.

purines and pyrimidines

Chemotherapeutic agents that are chemically modified natural products of microorganisms are most specifically referred to as __________.

semisynthetic drugs

Chemotherapeutic agents that are artificially produced are most specifically referred to as __________.

synthetic drugs

The drug level required for the clinical treatment of a particular infection is called the _________.

therapeutic dose

The ratio of toxic dose to therapeutic dose is called the _________.

therapeutic index

Medicinal chemists that synthesize drugs to kill pathogenic protozoans aim to target a novel mechanism to promote selective toxicity. The reason there are fewer antiprotozoal drugs compared to antibacterials is that __________.

there are few novel molecular mechanisms in protozoa compared to human hosts since both are eukaryotes, so toxicity is an issue

Fluoroquinolones are known to damage tendons and nerves in patients taking the drug. Side effects from quinolones are unavoidable because __________.

they inhibit DNA synthesis, and bacteria and eukaryotes carry out very similar mechanisms for DNA replication

Developing antiprotozoal drugs is a challenge for medicinal chemists due to the fact that novel protozoan targets are limited since both pathogen and host are eukaryotes.

true

Development of drug resistance is encouraged by _________.

widespread use of broad-spectrum drugs

1. Fusion inhibitor 2. Reverse transcriptase inhibitor 3. Protease inhibitor 4. Integrase inhibitor

1. Viral and cell membranes unite to deliver the viral genome to the host cytoplasm. 2. The host cell synthesizes the viral genome using the viral RNA as template. 3. Viral proteins are synthesized and processed. 4. Viral DNA is incorporated into the host chromosome.

1. target modificiation 2. drug inactivation 3. efflux pumps 4. alternate pathway

1. modifiy the antibiotic target, change the terminal D-alanine in peptidoglycan 2. hydrolysis of the B-lactam ring of penicillins by pencillinase 3. pump the drug out of the cell after it has entered, drug/proton antiporters 4. bypass the sequence inhibitied by the agent, use preformed folic acid from their surroundings

1. cell wall inhibitor 2. protein synthesis inhibitor 3. nucleic acid synthesis inhibitor 4. antimetabolites

1. penicillins, cephalosporins, vanocomyocin 2. aminoglycosides, macrolides, tetracyclines, lincosamines, chloramphenicol 3. quinolines, rifampin 4. sulfonamides, isoniazid, trimethoprim

The accompanying graph illustrates the relationship between the MICs of a hypothetical drug and the size of the zone of inhibition around a disk in which microbial growth is inhibited. In order to be a candidate for treatment in a patient, a pathogen isolated from a patient should not exhibit a zone of inhibition less than _________ in diameter when tested with this drug.

17 mm

The aminoglycosides and tetracyclines specifically target the ____________ interfering with ____________.

30S ribosomal subunit; protein synthesis

Which of the following is likely to have the most toxic side effects to humans?

Disrupters of cell membrane structure

Identify all the ways that could help slow the emergence and spread of antimicrobial resistance.

Have health care workers observe patients taking their antibiotic dose, to ensure compliance with the antibiotic regimen. Administer two or three drugs simultaneously to prevent the emergence of resistance to one drug. Encourage appropriate administration of drugs (don't overprescribe).Educate patients on the proper use of prescribed drugs (don't skip a dose).

Which of the following is not true of an effective antibacterial drug?

It should target the plasma membrane since this is the one structure that bacteria and host cells have in common.

Choose the method of antimicrobial susceptibility testing that involves measuring and evaluating diameters of zones of inhibition around antibiotic disks placed on a culture of bacteria prior to incubation.

Kirby-Bauer test

Select all the different mechanisms by which antiviral medications work.

Preventing entry of the virus into the host cell, Blocking viral nucleic acid synthesis, Preventing the maturation of viral particles

Examine the zone diameter data in the table. Choose the statement that represents a valid conclusion from these data.

Pseudomonas is less susceptible to carbenicillin than E. coli.

Which of the following antibiotics specifically inhibits DNA synthesis?

Quinolones

Rationalize why HIV-positive patients are given a "cocktail" of drugs rather than a single antiviral agent to target the virus?

Reverse transcriptase, used by HIV for nucleic acid synthesis, cannot proofread for errors so mutations leading to multiple drug resistance are common.

Select the response that describes a broad-spectrum drug.

A drug that is effective against E. coli (Gram-negative) and Staphylococcus aureus (Gram-positive)

Penicillin remains one of the most effective drugs against bacteria. This is due to ________.

All of the choices are correct.

Choose the statement that correctly explains how an antibiotic that inhibits protein synthesis can be selective.

Antibiotics bind to the 70S bacterial ribosomes but not to the 80S eukaryotic ribosomes.

Which of the following is sometimes useful against viral infections?

Azidothymidine

Which of the following is NOT true about Kirby-Bauer disk diffusion method?

Bacteria used to swab plate a test plate should be at least a week old.

Antifungals have a selective toxicity that targets which aspect of fungal cell biology?

Cell membrane synthesis

Finally, the ____ uses a convenient test strip impregnated with increasing concentrations of the antibiotic.

Etest

Who is usually credited with the discovery of penicillin?

Fleming

Why are there far fewer antifungal agents than there are antibacterial agents?

Fungal cells are much more similar to human cells than are bacterial cells.

Who is generally credited with the discovery of sulfanilamide as a chemotherapeutic agent?

Gerhard Domagk

Why does treatment to combat HIV/AIDS typically involve drug combinations?

HIV frequently develops drug resistance.


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