LEC 15 - Introduction to Chemotherapy Flashcards by Raegan Chambers

What bacterial group is most commonly the ones that undergo conjugation?

Gram-negative

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What drugs cannot be used in food animals? (8)

Fluoroquinolones

Chloramphenicol

Nitroimidazoles

Furazolidone

Nitrofurazone

Nitrofurans

Sulfonamides - lactating cattle

Vancomycin

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Mechanism of action - Macrolides

50S

Inhibits translocation

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Drugs for: Cell membrane

Polymyxins

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Component of transformation -

Free DNA

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What are the five chemotherapy agents that cause renal toxicity?

Cephalosporins

Vancomycin

Aminoglycosides

Sulfonamides

Amphotericin

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Mutation type for Quinolone resistance?

Gyrase gene mutation

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Mechanism of resistance - Beta lactams

Penicillinase

Modification of PBP’s

Change of porins

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How is Staph Aureus resistant?

Penicllinase via a plasmid

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Mechanism of action - Fluoroquinolones

Inhibiting topoisomerase

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How is multiple drug resistance transmitted between bacteria?

Plasmids

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How does conjugation pass along antibacterial resistance?

Passage of genes from cell to cell by DIRECT CONTACT through sex pilus or bridge

Can spread multi-drug resistance

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How does transformation cause resistance to be passed along?

Incorporation of DNA that has been found free in the environment into the bacterial genome

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What are the eight chemotherapy agents that cause hepatotoxicty?

Tetracyclines

Erthromycin estolate

Clindamycin

methotrexate

6-mercaptopurine

Sulfonamides

Amphotericin B

Doxorubicin

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What are the two chemotherapy agents that cause photosensitivity?

Tetracyclines

Fluroquinolones

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Component of conjugation -

Transfer of genes through sex pilus

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Describe bactericidal activity

No remarkable difference between bacteriostatic and bactericidal concentrations

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Drugs for: Protein synthesis 50s

Erythromycin

Chloramphenico

Clindamycin

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What are the three methods by which horizontal transfer can occur?

Transformation

Transduction

Conjugation

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Mechanism of action - Sulfonamides

Inhibition of folic acid synthesis

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What are the two drugs that can cause hemolytic anemias?

Sulfonamides

Nitrofurantoin

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What are the ways resistance can be acquired?

Vertically

Horizontially

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Drugs for: DNA-Dependent RNA polymerase

Rifampin

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Mechanism of action - Chloramphenicol

50S

Inhibit transpeptidation

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What are the three antibacterial agents that have become useless due to an increase in resistance in previously susceptible cells?

Streptomycin Quinolones Rifampin

What are the six mechanisms that a bacteria can be resistant to a drug?

Fails to absorb drug Inactivates the drug Pumps out drug Target to drug is modified Increased production of target molecules Altered metabolic pathway bypassing drug target

Mechanism of resistance - Sulfonamides

Decreased sensitivity of the target enzymes increased formation of PABA Use of exogenous folate

Drugs for: DNA replication

Nalidixic acid Quinolones

What are the major adverse affects that occur with chemotherapy agents?

overextenstion of actions organ directed toxcity Hypersensitivy reactions

Mechanism of resistance - Aminoglycocides

Acetyl Phophosryl Adenylyl conjugation

Mechanism of resistance - Chloramphenicol

Inactivating acetyltransferases

What is a common resistance that occurs with transformation? What bacterial types?

Penicillin resistance Pneumococci + Neisseria

Mechanism of action - Tetracyclines

30S Prevent binding the incoming charged tRNA

What are the three drugs that cause ototoxicity?

Aminoglycosides Vancomycin Minocycline

Mechanism of resistance - Tetracyclines

Pump out

Why is it important to reach and maintain adequate blood levels of a chemotherapy agent?

Prevents the development of resistance

What is the mechanism that Penumococci is resistant to penicillin?

Produce altered penicillin-binding proteins that have low affinity binding of penicillin

Why is sulfonamides such a concern in food animals?

Accumulate in the kidney Withdrawl times are long + highly variable

What method of acquired resistance is the most succesful

Plasmid involved resistance - When entered into the genome of the bacteria only 50% off the daughter cells will get the mutation

What does it mean for a drug to be time dependent when it comes to killing?

Killing is not increased with increasing concentrations about MBC

What two bacterias commonly use conjugation for passing along resistance?

Shigella + Enterobacteriaceae Can exchange between one another as well

Mechanism of resistance - Vancomycin

Change in pentapeptide D-ala-D lactate

What antibactieral agents is Staph Aureus resistant to?

Eryhtromycin Tetracycline Chloramphenicol

Mechanism of resistance - Macrolides

Methyltransferase alters the binding site

Mechanism of action - Beta Lactams

Inhibition of bacterial cell wall synthesis

Drugs for: Folic acid metabolism

Trimethoprim Sulfonamides

Component of transduction -

Bacteriophages

Mechanism of resistance - Rifampin

Change in enzyme

What are the two methods by which bactericidal agents kill?

Concentration dependent Time dependent

Drugs for: Protein synthesis - 30s

Tetracycline Spectinomycin Sterptomycin Gentamincin/Tobramycin Amikacin

What two drugs are concentration dependent?

Aminoglycocides Quinolones

What does it mean for a bactericidal agent to be conentration dependent killing?

Rate and extent of killing dependent upon drug concentration

Mutation type in Rifampin resistance?

RNA polymerase gene mutation

What are the four ways that allergic reactions to these chemotherapy agents might present?

Anaphylactic shock Skin rashes Immune induced blood dyscrasias Immune hemolytic anemias

Where does conjugation tend to take place?

Intestinal tract - between nonpathogenic and pathogenic microorganisms

How does transduction cause resistance?

Invervention of a bacteriophage that has bacterial DNA incorporated within the protein coat

Mutation type for streptomycin resistance?

Ribosomal mutation

What are the two specific agents that are known to be hemopoietically toxic?

Chloramphenicol Sulfonamides

What are the special components to chemotherapy?

Selective toxicity (Parasite \> Host) Selects for resistant strains Hypersensitivity + Organ directed toxicity Lowers microorganism load (Host defense does the rest)

Drugs for: Periplasmic space

B-lactamases Aminoglycosides

What two drugs are time dependent when it comes to their -cidal effects?

Beta-lactams Vancomycin

What is exchanged in conjugation between bacteria?

R-determinant plasmid risstance transfer factor (RTF)

Describe bacteriostatic drugs

Bacteriostatic concentrations much lower than bactericidal

What drug is there a voluntary ban in food animals?

Sulfonamides

Mechanism of resistance - Fluoroquinolones

Change in sensitivity of TI "Pump out"

Drugs for: Cell wall synthesis

Cycloserine Vancomycin Bactitracin Penicillins Cephalosporins

Mechanism of action - Vancomysin

Inhibition of peptidoglycan chain elongation

Mechanism of action - Aminoglycosides

30S Blocks initiation Elicits premature termination by incorporating incorrect AA

Mechanism of action - Rifampin

Inhibits DNA dependent RNA polymerase

What bacteria is known for using transduction to spread resistance?

Staph. Aureus

When is maintaince of constant blood levels most important?

With bacteriostatic drugs more so than bactericidal

How is resistance vertically passed?

Mutation occurs Passed to offspring by selection