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Antiviral drugs work by being...

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analogs of components of viral DNA or RNA

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Acyclovir and AZT (azidothymidine) are nucleotide analogs in treatment of

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HIV
Acyclovir treats Herpes virus

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When nucleotide analogs become incorporated into the pathogen’s DNA:

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Distorts the shape of pathogen’s DNA and RNA
Which prevents replication, transcription, or translation

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Nucleotide analogs make potent antiviral and anticancer drugs because…

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Viruses and cancer cells typically replicate faster than normal cells.

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Viruses are _______ more likely to incorporate an analog into the viral DNA or viral RNA than host the cell.

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100X

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Spectrum of action

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The number of different kinds of pathogens a drug acts against

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Diffusion susceptibility test AKA...

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Kirby-Bauer test

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Diffusion susceptibility test procedure

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1. Uniformly inoculate Petri plate w/pathogen
2. Small disks of drugs are firmly arranged on the plate
3. Plate is incubated for _____ hours and examined
4. Plates are examined for zones of inhibition
5. Larger the zone of inhibition = more effective drug

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Researchers classify drugs as:

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Susceptible, Intermediate, Resistant to each drug

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Diffusion Susceptibility Test tells us:

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1. Which drug is the drug of choice.
2. Which drug is the microbe most susceptible to.

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MIC test:

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lowest dosage of that the drug of choice will most be effective

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MIC test procedure:

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Series of dilutions of the drug of choice is place in nutrient broth
Standard amount of bacteria is added to each broth tube.
After incubation, clear broth indicates that bacteria were either inhibited or killed

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MIC is:

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bacteriostatic

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MBC test:

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determines the dosage of the drug to be an effective bacteriocidal.

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MBC Samples are taken from and transferred to:

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clear MIC tubes or zones of inhibition of Diffusion Susceptibility Test = Kirby Bauer, to plates containing a drug-free growth medium

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Any growth of bacterial colonies on a MBC plate indicates that concentration of antimicrobial drug is…

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Only bacteriostatic not bactericidal

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List routes of drug administration:

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Topical or Local
Orally
Intramuscularly (IM)
Intravenously (IV)

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Topical or local =

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Application of drug if infection is external

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Oral – simplest

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Lower drug concentrations
No reliance on health care provider
Patients do not always follow prescribing information
Patients may quit taking the drug

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Intramuscular

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Requires needle for administration
Some patients refuse shots
Reaches a higher drug concentration faster than oral administration
Drug concentration diminishes as liver and kidneys remove drug from circulation
Concentration never as high as IV administration

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Intravenous

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Requires needle or catheter
Drug in blood is initially very high drug concentration
Remains high, constant delivery

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What are three main categories of side effects?

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Toxicity
Allergies
Disruption of normal microbiota

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Toxicity:

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Ideally antimicrobials drugs are toxic to pathogens and harmless to humans; however many drugs have toxic side effects
Exact cause of many adverse reactions poorly understood
Many Drugs may be toxic to kidneys, liver, or nerves

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Flagyl

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Antiprotozoan drug

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Flagyl may cause a harmless temporary condition called

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“black hairy tongue”

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Tetracycline causes

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discoloration of teeth

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Toxicity in pregnant women causes:

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side effects to the fetus (accutane)

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Allergies: Some drugs trigger allergic:

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immune responses

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Although allergic reactions are rare, they may be:

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life threatening and may cause Anaphylactic shock

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.1% of Americans have anaphylactic reactions to:

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Penicillin

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Disruption of Normal Microbiota/Flora

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May allow opportunistic pathogens to increase and result in secondary infections

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Long term use of broad spectrum antimicrobials often result in:

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explosion of overgrowth of normal flora: Candida albicans

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Candida albicans of the vagina and mouth:

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causes vaginitis yeast infection and thrush after long term

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Superinfections or multiplication example:

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Clostridium difficile

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Clostridium difficile normally resides ______ is held in check by _________.

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in the colon; normal microbiotica/normal flora

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If normal flora is destroyed by long term treatment of antibiotics; C. difficle can multiply and causes a potentially fatal condition called:

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Pseudomembranous colitis

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Secondary infections like C. difficile are of greatest concern for hospitalized patients that are already:

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immumocompromised and exposed to resistant pathogens

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Not all microbes of the _________ are equally sensitive to a given drug

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same population

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mutant strains are:

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naturally partially or completely resistant to a given drug

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In the absence of antimicrobial agents, the resistant (mutant) cells are:

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in the minority and usually less efficient than normal cells

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When antimicrobial agent is present, sensitive cells are _______ while the resistant cells

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inhibited or die continue to grow

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Resistant cells then replace:

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sensitive cells as the majority in the population

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Antimicrobials do not produce:

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resistance!

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Bacteria can acquire resistance in 2 ways:

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1. New mutations of chromosomal genes
2. Acquisition of R-plasmids via transformation, transduction, and conjugation

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What are 5 ways bacteria develop resistance?

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1. Can mutate their DNA to produce enzymes
2. Can mutate their DNA to alter the shape of proteins called porins
3. Can alter receptors that so that drug can no longer attach to it or drug binds less effectively to microbe
4. Can alter their metabolic pathways that the drug targets
5. Pump the drug out of the cell before the drug can act

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Resistant Microbes mutate their DNA to produce enzymes such as beta-lactamase (Penicillinases enzyme) that destroys (it opens the B-latam ring) or deactivates the beta-lactam of drug- ex:

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Penicillinases enzyme renders penicillin inactive (MRSA)

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Resistant Microbes mutate their DNA to alter the shape of proteins called porins in microbe’s cell membrane- ex:

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These mutated porin slows or prevents entry of drug into the cell.
Mutated porins give bacteria resistant to penicillin and tetraclycine

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Resistant Microbes alter receptors that so that drug can no longer attach to it or drug binds less effectively to microbe - ex:

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(HIV and Trypanosoma brucei alter their receptors through mutation)

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Resistant Microbes alter their metabolic pathways that the drug targets- ex:

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Example: Resistance against Sulfa Drugs
1. Produce more PABA
2. Resistant microbes abandon synthesis of folic acid and absorb it from the environment

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Antimicrobials facilitate replication of resistant cell that were:

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already in population

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What is Multiple Resistance?

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Pathogen can fight off to more than one drug at a time Especially when different R-plasmids are exchanged

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Multi-resistant strains of bacteria develop in:

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Hospitals and nursing homes, where the constant use of many kinds drugs eliminates sensitive cells and allows the growth of resistant strains

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What is Cross Resistance?

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When one antimicrobial agent
can fight more than one drugs
Especially when drugs have similar structures

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Examples of Cross Resistance

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Streptomycin, Neomycin, Gentamicin, Kanamycin

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Multiple Resistance and Cross Resistance create:

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superbugs.

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Superbugs:

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pathogens that are resistant to many drugs

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Ex. Of Superbug strains:

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Staphylococcus, Streptococcus, Enterococcus, Pseudomonas, Plasmodium

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Four ways to Retard the Develop of Resistance:

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High concentrations of drug maintained in patient for long enough time to kill all the pathogen’s sensitive cells and inhibit resistant cells long enough for immune system to destroy them.
Use a combination of antimicrobial agents so that pathogens resistant to one drug will be killed by another drug
Limit use of antimicrobials to necessary cases
Develop new variations of existing drugs to resistant strains
Second-generation drugs then Third-generation

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Synergistic drugs:

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one drug enhances the effect of a second drug Example: Penicillin and streptomycin

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Penicillin inhibits the formation of the:

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cell wall and makes it easier for streptomycin to get inside the pathogen and interfere with protein synthesis

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Antagonistic drugs:

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drugs that interfere with each other
Example:
Drugs that slow bacterial growth are antagonistic to drugs that act only against growing and dividing cells

OCTC-Micro-Chapter 10 – Flashcards

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