Chemotherapy I/II Flashcards by Rebecca Lea

Receptor-Effector concept

specific bullets to kill bacteria

salvarsan

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Selective toxicity of chemotherapy

need greater toxicity to parasite than host

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What are two potential problems associated with chemotherapy

hypersensitivity and organ directed

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How does chemotherapy work

lowers the microorganism load so that the host defense system can get rid of the foreign organisms from the body

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Three adverse effects of antimicrobial therapy

overextensions of pharmacologic actions

organ directed toxicity

hypersensitivity reactions

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What six drugs lead to hepatotoxicity?

tetracyclines

isoniazid

erythromycin estolate

clindamycin

sulfonamides

amphotericin B

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Which five drugs lead to renal toxicity?

cephalosporins

vancomycin

aminoglycosides

sulfonamides

amphotericin B

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Which three drugs are associated with ototoxicity?

aminoglycosides

vancomycin

minocycline (vestibular only)

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Which two drugs are associated with visual toxicity?

ethambutol

isoniazid

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Which two drugs (plus one class of drugs) leads to hemopoietic toxicity?

many antiviral agents

chloramphenicol

sulfonamides

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What are some drug allergy symptoms? (4)

anaphylactic shock

skin rashes

immune induced blood dyscrasias

immune hemolytic anemias

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Which two drugs are associated with hemolytic anemias?

sulfonamides

nitrofurantoin

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Which three drugs are associated with photosensitivity?

tetracyclines

fluroquinolones

sulfonamides

** high risk for secondary infections

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With chemotherapeutic agent which six things need to be considered with host, pathogen factor, and chemotherapeutic agent?

metabolism of host
toxicity of chemotherapeutic agent
disease caused by pathogen factor
host’s defense system
resistance of host
therapeutic effect on pathogen factor
pathogen’s resistance against chemotherapeutic agent

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What are the five general mechanisms of action on microorganisms?

inhibit synthesis of cell wall
damage outer membrane
modify nucleic acid or DNA synthesis
modify protein synthesis (at ribosomes)
modify energy metabolism within the cytoplasm (at folate cycle)

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Chemotherapy selects for

drug resistant stains

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What two types of drug resistance are there?

natural and acquired

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Mechanism for resistance:

pathogen or cell fails to:

absorb drug

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Mechanism for resistance:

pathogen or cell

inactivates drug

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Mechanism for resistance:

pathogen or cell

pumps drug out (MDR, p-glycoprotein)

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Mechanism for resistance:

drug target is ______ thus resistant to drug

modified

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Mechanism for resistance:

increased production of

target molecules

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Mechanism for resistance:

altered metabolic pathway

bypasses drug target

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How does multiple drug resistance occur?

transmitted by plasmids

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Antimicrobial resistance is acquired by: a mutation and passed ______ by selection to daughter cells

vertically

Antimicrobial resistance is acquired by ______ ____ of resistance determinants from a donor cell, often of another bacterial species.

horizontal transfer

Three examples of horizontal transfer

transduction (bacteriophages) transformation (incorporation of free DNA) conjugation (transfer of genes through sex pilus)

Transduction uses a __________ to incorporate donor DNA into recipient bacterium

bacteriophage

In transduction, what type of DNA will receipient bacterium have?

bacteriophage DNA and bacteria's DNA

How does transformation work?

Bacterial cell lysed --> new bacteria picks up a bacterial chromosome from lysed cell and that bacterial chromosome gets incorporated into bacterial cell's DNA

How does conjugation work?

Direct cell-to-cell contact. 2 bacterial cells - 1 has a mobile blasma and pilus. Pilus from donor cell attaches to recipient cel Relaxosome connects donor cell to the transferosome of recipient cell. Now, the recipient cell has been injected with mobile plasmid.

What does horizontal transfer result in?

multiple drug resistance

What type of bacteria is particularly susceptible to horizontal transfer?

gram (-)

6 causes of antibiotic resistance?

over-prescribing of antibiotics patients not finishing tx over-use of antiobiotics in livestock and fish farming lack of new antibiotics being developed lack of hygiene and poor sanitation poor infection control in hospitals and clinics

Penicillin-resistant strains of ______ account for 50% or more of isolates in some European countries and the proportion of such strains is rising in US

pneumococci

Worldwide emergency of _____ and _____ that produce b-actamase is major therapeutic problem

Haemophilus and gonococci

Methicillin-resistant strains of _________ are widely distributed among hospitals and are increasingly isolated from community-acquired infections.

S. aureus (MRSA)

There are now strains of ______, _____, and _____ that are resistant to all known drugs.

enterococci, pseudomonas, enterbacters

Epidemics of multiple drug-resistant strains of ________ have been reported in US.

M. tuberculosis

Antimicrobial agents are frequently used ____ the _____ responsible for the illness or susceptibility to a particular antimicrobial agent is known. This is called empirical antimicrobial therapy.

before the pathogen

Empirical antimicrobial therapy is based on

experience

Choice of antimicrobial agents depends on

host factors - immunocompromised, liver damage, kidney damage, age, dosing requirements, costs, etc.

In empirical antimicrobial therapy, you must obtain a culture before/after prescribing antibiotic.

BEFORE then formulate dx. change therapy if needed.

Example of narrow spectrum antimicrobial drug

isoniazid

Example of extended-spectrum antimicrobial drug

ampicillin

Example of broad-spectrum antimicrobial drug

tetracycline

What kind of spectrum is going to have the most adverse side effects?

broad spectrum

What kind of spectrum will treat the most infections

broad-spectrum

Broad spectrum antibiotics disrupt

natural flora everywhere

Empirical therapy timeline: mixed infection suspected

infected pt --> take specimens for identification and sensitivity testing --> empirical therapy - coverage by antibiotics effective against Gram-positive, gram-negative, and anaerobes --> receive culture report with sensitivities IF only a gram negative infection, patient's tx needs to be adjusted to only tx gram-negative infections. Same with gram positive. If mixed - continue therapy as initiated

bacteriocidal

cell death

bacteriostatis

growth inhibition stops growth which allows immune system to take care of infection

Zone of clearance is the zone where

bacteria cannot grow.

Can you tell if antibiotic is cidal or static using agar?

No. Clearing just tells you if organism is sensitive to antibiotic

increased zone of clearance means

increased sensitivity

when to use bacteriocidal?

bactericidal - no remarkable difference between bacteriostatic and bactericidal concentrations

when to use bacteriostatic?

inhibitory concentrations are much lower than bactericidal

When you remove a bacteriostatis agents, what happens if you do not have a robust immune system?

starts growing again. while bacteriostatic agent is present, growth is halted but never dies off, therefore when agent is removed and immune system has not cleared the bacteria, it will begin growing again

What happens with bacteriocidal agent is removed?

No regrowth.

If immunocompromised, what type of agent should we use?

bacteriocidal agent

It is important to reach and maintain ____ ____ ___ in order to prevent the development of resistance. Maintenance of constant blood levels is more important in what kind of agent?

adequate blood levels bacteriostatic than bactericidal agent

Concentration dependent killing

rate and extent of killing dependent upon drug concentration (aminoglucosides and quinolones)

Time dependent killing

killing is not increased with increasing concentrations above MBC (beta-lactams, vancomycin) but is dependent on time of exposure to antibiotic

What dictates how long to use an antibiotic?

time dependent killing

Concentration dependent killing must reach

certain concentration of drug to be bactericidal

What type of agents inhibit synthesis?

bactericidal - cell wall and DNA

What type of agents inhibit protein and metabolism

bacteriostatis

MIC

minimum inhibitor concentration - smallest concentration to keep cells from growing

MBC

minimum bactericidal concentration - smallest concentration to kil cells

PAE

postantibiotic effect

What is PAE?

persistent suppression of bacterial growth after limited exposure to an antimicrobial agent exact mechanism i unknown

Clinical importance of PAE

don't have to have dose given as often if PAE exists

Synergism

when inhibitory or killing effects of two or more antimicrobials used together are significantly greater than expected from their effects when used individually 2 + 2 = 7

Synergism mechanism Blockade of sequential steps in metabolic sequence

TMP - SMX

Synergism mechanism Inhibition of enzymatic inactivation

beta-lactamase inhibitors

Synergism mechanism Enhancement of

antimicrobial agent uptake

Synergism: penicillin and aminoglycans together Independently the cells are inhibited only (static)

Penicillin destroys cell walls so aminoglycans can gain entry -- cell death occurs (cidal)

Antagonism

inhibition of bactericidal activity by bacteriostatis agents 2 antibiotics don't work well together

Antagonism: induction of enzymatic inactivation: some gram-negative bacilli contain

inducible beta lactamases drug-drug interactions that nullify effects

Chemotherapy I/II Flashcards

(79 cards)