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Chapter 12
Drugs, Microbes, Host; The Elements of Chemotherapy
51
Microbiology
Undergraduate 3
11/19/2012

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Term
Antibiotic
Definition
A chemical substance from one microorganism that can inhibit or kill another microbe even in minute amounts.
Term
Selectively toxic
Definition
Drugs should kill or inhibit microbial cells without simultaneously damaging host tissues.
Term
Spectrum
Definition
Range of activity of a drug.
Term
Narrow-spectrum
Definition
Effective on a small range of microbes.
-target a specific cell component that is found only in certain microbes.
Term
Broad-spectrum
Definition
Greatest range of activity.
-target cell components common to most pathogens.
Term
Medium-spectrum
Definition
Effective on both gram + and gram - bacteria but not all.
Term
Antiviral drugs
Definition
Any drug that destroys viruses via analogs of purines and pyrimidines.
-These insert in viral nucleic acid, preventing replication.
Term
Synergistic effect
Definition
Increased intensity (effectiveness) caused by the combination of two substances on an organism, lowering the required dose of each.
Term
Competitive inhibition
Definition
Control process that relies on the ability of metabolic analogs to control microbial growth by successfully competing with a necessary enzyme to halt the growth of bacterial cells.
Term
MIC (Minimum Inhibitory Concentration)
Definition
The lowest concentration of antibiotic needed to inhibit bacterial growth in a test system.
Term
Parententerally
Definition
To be outside of the intestine.
Term
Drug resistance
Definition
An adaptive response in which microorganisms begin to tolerate an amount of drug that would ordinarily be inhibitory.
Term
Acquired resistance
Definition
Refers to specific immunity developed by lymphocytes responding to antigens.
Term
Kirby-Bauer disk diffusion test (part 1)
Definition
This technique is an agar diffusion test that provides useful data on antimicrobial susceptibility. In this test, the surface of a plate of special medium is spread with the test bacterium, and small disks containing a pre-measured amount of antimicrobial are dispensed on to the bacterial lawn.
Term
Kirby-Bauer disk diffusion test (part 2)
Definition
After incubation, the zone of inhibition surrounding the discs is measured and compared with a standard for each drug. the profile of antimicrobial sensitivity provides data for drug selection. This procedure is less effective for bacteria that are anaerobic, highly fastidious, or slow-growing (Mycobacterium).
Term
Therapeutic index (TI)
Definition
Defined as the ratio of the doe of the drug that is toxic to humans as compared to its minimum effective (therapeutic) dose. The closer these two figures are, the greater is the potential for toxic drug reactions.
Term
Prophylaxis
Definition
Use of a drug to prevent potential for infection of a person at risk.
Term
Semi-synthetic drugs
Definition
Drugs which are chemically modified in the laboratory after being isolated from natural sources.
Term
Interferons (IFN)
Definition
A glycoprotein produced primarily by fibroblasts and leukocytes in responds to various immune stimuli.It has numerous biological activities, including antiviral and anticancer properties. Studies have shown that it is a versatile part of animal host defenses, having a major role in natural immunities.
Term
What is the 1st of the 5 main mechanisms of Drug Action?
Definition
1) Protein Synthesis
-Penicillins
-Cephalosporins
-Vancomycin
-Bacitracin
-Monobactams/carbapenems
-Fosfomycin
-Cycloserine
-Isoniazd
Term
What is the 2nd of the 5 main mechanisms of Drug Action?
Definition
2) Breakdown of cell membrane structure/function
-Polymyxins
Term
What is the 3rd of the 5 main mechanisms of Drug Action?
Definition
3) Inhibition of structures and functions of DNA and RNA
-Inhibit gyrase (unwinding enzyme): Quinolones (ciprofloxacin)
-inhibit RNA polymerase: Rifampin
Term
What is the 4th of the 5 main mechanisms of Drug Action?
Definition
4) Inhabitation of protein synthesis
-Action site of 50s subunit: Chloramphenicol, Erythromycin, Clindamycin, Oxazolidinones
-Action site of 30s subunit: Aminoglycosides, Tetracyclines, Streptomycin, Amikacin
Term
What is the 5th of the 5 main mechanisms of Drug Action?
Definition
5) Blocks key metabolic pathways
-Sulfonamides (sulfa drugs)
-Trimethoprim
Term
What is the primary mode of action of all Beta-lactam drugs?
Definition
Interfere with proteins involved in synthesis of the cell wall, leading to lysis and cell death. more than half of all antimicrobic drugs are beta-lactams, with penicillins and cephalosporins being the most prominent representatives.
Term
What are the 2 natural forms of Penicillin that are most important?
Definition
Penicillium notatum and Penicillin V
Term
What types of bacteria are the natural forms used against?
Definition
Gram - bacteria that are sensitive. Commonly found in the form of wound pathogens.
Term
What types of bacteria are the semisynthetic forms used against?
Definition
Gram - bacilli
Term
Why is semisynthetic Penicillin often better?
Definition
-Resistance to stomach acids so that they can be taken orally.
-A degree of resistance to penicillinase (a penicillin-destroying enzyme produced by some bacteria).
-Extended range of activity against some Gram - bacteria.
Term
What are the primary problems with Penicillins?
Definition
Widespread development of resistance among target microorganisms and allergic reaction.
Term
What is the primary mode of action of Cephalosporins?
Definition
Inhabitation of cell-wall synthesis.
Term
Why are Cephalosporins sometimes superior to Penicillins?
Definition
Relatively broad-spectrum, resistant to most penicillinases, and cause fewer allergic reactions.
Term
What are some cephalosporins of the 3rd and 4th generations?
Definition
3rd Gen: broad-spectrum activity against enteric bacteria with beta-lactamases.
-Cephalexin, Ceftriazone

4th Gen: Widest range; both Gram - and Gram +
-Cefepime
Term
What type of infection is Vancomycin used for? What are its drawbacks?
Definition
Type: Narrow-spectrum, most effective in treatment of Staphylococcal infections in cases of Penicillin and Methicillin resistance or if patient is allergic to Penicillin.

Drawbacks: Toxic and hard to administer, restricted use.
Term
What is Bacitracin used for?
Definition
Narrow-spectrum range produced by a strain of Bacillus subtilis; used topically in ointment.
Term
What is Aminoglycosides mode of action? What type of infection are they used for?
Definition
Mode of action: Broad-spectrum. Inhibits protein synthesis.

Infection type: Aerobic Gram - rods and certain Gram + bacteria.
Term
What are some examples? What are some specific diseases treated by using Aminoglycosides?
Definition
Examples:
-Streptomycin (Bubonic Plague, Tularemia, TB)
-Gentamicin (Less toxic, used against Gram - rods)
-Tobramycin and Amikacin (Gram - bacteria)

Diseases: Bubonic Plague, Tularemia, and Tuberculosis.
Term
That is Tetracycline Antibiotics' mode of action? What types of infection are they used for?
Definition
Mode of action: Broad-spectrum. Blocks protein synthesis by biding ribosomes.

Infection type: STD's, Rocky Mountain Spotted Fever, Lyme Disease, Typhus, Acne and Protozoa.
Term
What is Tetracycline's advantage? What concern is there?
Definition
Advantage: Low cost of oral drugs.

Concern: Side effects, such as reaction to sunlight while taking this antibiotic.
Term
That is Chloramphenicol's mode of action? What types of infection is it used for?
Definition
Mode of action: Potent broad-spectrum drug with unique nitrobenzene structure. Blocks peptide bond formation (i.e. protein formation)

Infection types: typhoid Fever, Brain Abscesses, Rickettsial and Chlamydial infections for which there are no other treatments (intracellular bacteria.)
Term
What concern is there when using Chloramphenicol?
Definition
Concern: Toxic to people. Tis leads t restricted use, can cause irreversible damage to bone marrow.
Term
What is Macrolides' mode of action? What types of infection are they used for?
Definition
Mode of action: Broad-spectrum, fairly low toxicity.

Infection types: Mycoplasma pneumonia, legionellosis, Chlamydia, Pertussis, Diphtheria and as a Prophylactic prior to intestinal surgery.
Term
What is the major infection type of Macrolides used to treat? What do you use when someone is resistant to Erythromycin?
Definition
Major infection type: Streptococcus pneumoniae

Alternatives: Ketolides- Telitromycin (Ketek), new class of drugs with different ring structure from Erythromycin; used for infection when resistant to Macrolides.
Term
What are Sulfa drugs' mode of action? What are they used to treat?
Definition
Mode of action: Narrow-spectrum; block the synthesis of folic acid by bacteria.

Infection types:
-Sulfisoxazole: Shingellosis, UTI, and protozoan infections.
-Silver sulfadizine (silvadine): burns, eye infections.
-Trimethoprim: given in combination with sulfamethoxazole to treat UTI, Pneumocystis pneumonia, and ear infections.
Term
What is Macrolide polyenes used to treat? What is it's mode of action?
Definition
Macrolide polyenes: Produces holes in fungal membranes.
-Amphotericin B: mimics lipids, most versatile and effective, topical and systemic treatments.
-Nystatin: topical treatment.
Term
What is Azoles used to treat? What is it's mode of action?
Definition
Azoles: Borad-spectrum; inhibits the enzymes necessary to convert Lanosterol to Ergosterol.
-Ketoconazole
-Clotrimazole
Term
What is Flucytosine used to treat? What is it's mode of action?
Definition
Flucytosine: Analog of Cytosine; cutaneous mycoses or in combination with Amphotericin B for systemic mycosis.
Term
What are the 3 modes of action of antiviral compounds?
Definition
1) Block penetration into host cell.

2) Block transcription or translation of viral genetic material.
-Nucleotide analogs
-Acyclovir: Herpes viruses
-Ribavirin: a guanine analog - RSV, hemorrhagic fevers
-AZT: Thymine analog - HIV

3) Prevent maturation of viral particles.
-Protease inhibitors - HIV
Term
What are the different mechanisms of drug resistance? (1-2)
Definition
1) Drug inactivation by acquired enzymatic activity.
-ex: Penicillinases.

2)Decreased permeability to drug or increased elimination of drug from cell.
-Via acquisition or mutation.
Term
What are the different mechanisms of drug resistance? (3-5)
Definition
3) Change in drug receptors by mutation or acquisition.

4) Change in metabolic patterns.
-Mutation of original enzyme.

5) Possession of "pumps" that are able to move drugs outside of the cell wall.
Term
What are some considerations in selecting an antimicrobial drug?
Definition
1) Identifying the microorganism causing the infection.

2) Test the microorganism's susceptibility (sensitivity) to various drugs "in vitro" when indicated.

3) The overall medical condition of the patient.
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