antimicrobial medications on-line

8/11/2019 Antimicrobial Medications on-line

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Antimicrobial Medications

Kathy Huschle

Northland Community and Technical College


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HistoryPaul Ehrlich 1910

Upon making the observation that some dyes stainedbacterial cells, but not animal cells, Ehrlich determined

that there was a fundamental difference between the 2

types of cells. He began the search for the magic bullet-

a drug that would kill a microbial pathogen withoutharming the human host.


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History

After 605 tests to find a cure for syphilis, Ehrlich wassuccessful in 1910. He proved that arsphenamine, a

compound of arsenic, was effective in treating lab

animals. The ability of the new drug, named

Salvarson, to cure syphilis, proved that chemicalscould be used to selectively kill microorganisms without

harming the human host permanently.

Paul Ehrlich


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History

Gerhard Domagk 1932

accidentally discovered the first sulfa drug,

sulfanilamide, while testing a red dye called Prontosil

on streptococci

Gerhard

Domagk


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History

Fleming 1928 noticed that colonies of Staphylococcuswere

inhibited by mold

Fleming identified the mold as a species of

Penicilliumwith further testing, it was shown that Penicillium

was a bacteria-killing substance

Alexander

Fleming


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History

Ernst Chain & Howard Florey successfully purified penicillin

1941 - 1st test on an ill human

the patient improved dramatically,

but died when the penicillin ran out mass development of penicillin was

spurred on by WW2

first antibiotic developed for the

general public

Sir Howard Florey

Dr. Ernst Chain


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Terms

chemotherapeutic agent any drug used for any medical condition

antimicrobial drug

a chemical that destroys pathogens, includes

antibiotics and chemically synthesized drugsantibiotic

an antimicrobial agent produced naturally by a

bacterium or fungus

bactericidal capable of killing a microorganism

bacteriostatic

inhibits the growth of microorganisms


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Features of Antimicrobial Drugs

the pharmacological properties of a potential

antimicrobial agent needs to be considered todetermine if the agent is the best for the particularinfection

properties that are considered include

selective toxicity spectrum of activity

distribution, metabolism, excretion

interaction between drugs

adverse effect resistance


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Selective Toxicity

antimicrobials

cause greater harm to microorganism than to human

host

are able to attack biological structures or functionsunique to the microorganism

non-toxic to humans is ideal, but realistically all

antimicrobial drugs can be harmful in high

concentrations


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Selective Toxicity

measurement of the toxicity of a drug is called the

therapeutic index

the therapeutic indexof a medication is a

comparison of the amount that causes the therapeutic

effect to the amount that causes toxic effects

a high therapeutic indexis LESS toxic to the patient

Penicillin G: high index

a low therapeutic indexrequires monitoring of thepatient to be certain that it does not reach a toxic level

if a drug is too toxic for the systemic (internal) system,

it may be used as a topical application


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Spectrum of Activity

refers to the range of microorganisms that a

antimicrobial agent can kill or inhibit

broad spectrum

affect a wide rangecan disrupt the normal flora of the body

used particularly in the cases of rapid onset life-

threatening infections, when there is no time to

culture the causative agent narrow spectrum

limited range

requires the identification of the pathogen


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Distribution, Metabolism, Excretion

antimicrobials have to get where they are needed

a drug that is destroyed by acid cannot be taken

orally

the rate of elimination is expressed as the half-lifeof the drug

the half-life is the time it takes the body to

eliminate 1/2 of original dose

knowing the half-life of a drug will determinehow frequently the doses have to be

administered

this is why some medications are prescribed

every four hours, others 2X per day


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Interaction Between Drugs

combined drug therapy sometimes necessary to use two antimicrobial

agents for successful treatment of an infection

it is possible that one antimicrobial agent could

influence the action of the other synergism

action of one antimicrobial agent enhancing theothers activity

antagonistic action

action of one interferes with the other

additive

neither synergistic or antagonistic


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Adverse Effects

most all antimicrobial agents have concerns and dangers

allergic reactions

toxic effects to the body such as kidney damage

suppression of normal floranormal flora is an important key to our immune

system

if it is altered too greatly, it can create an

imbalance of those friendly microorganisms


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Resistance

resistance to antimicrobial agents is of mounting concern

in the medical field

innate or intrinsic resistance can be found in

antimicrobial agents naturally

this natural resistance, leads to survival of the fittest,

or survival of those antimicrobial agents that are

resistant

this resistance is then inherited by the offspring


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Resistance


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Resistance

3 major mechanisms that lead to antimicrobial agents

resistance

inactivation of the antimicrobial agent by an enzyme

prevention of the antimicrobial agent from reaching itstarget cell structure

alteration of the target cell structure so that it is no

longer affected by the antimicrobial agent


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Mechanisms of Action of

Antimicrobials

different cell structures or microbial processes are

the targets of antimicrobial agents

structures that are different or absent from

eukaryotic cells

cell wall synthesis

protein synthesis

nucleic acid synthesis

metabolic pathways plasma membrane integrity


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Cell Wall Inhibitors

target peptidoglycan

peptidoglycan only occurs in bacteria, which makes it

an excellent target

penicillin, cephalosporin, vancomycin, bacitracin(topical)


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Protein Synthesis Inhibitors

all living organisms depend on protein synthesis

inhibitors act at different stages of protein

synthesis

there is enough difference in the ribosomalstructure (where proteins are synthesized)

between prokaryotic and eukaryotic cells

aminoglycosides

streptomycin, gentamicin, neomycin


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Protein Synthesis Inhibitors

chloramphenicol

last resort because of its rare, but life-

threatening side effects

the inability to form red or white blood cells

Proteins being tested with chloramphicol


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DNA Replication Inhibitors

target is the enzymes necessary for DNA replication

block bacterial DNA replication

fluoroquinolones

one of the enzymes inhibited is gyrase, whichprevents the unwinding of the DNA double helix

ciprofloxacin

rifamycins

blocks the initiation of transcription

rifampin


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Metabolic Pathway Inhibitors

very few of these agents are available

sulfonamides (sulfa drugs)

Trimethoprim

the above 2 drugs inhibit the metabolism of folic acid atdifferent steps in the process

animal cells lack these enzymes

makes folic acid a dietaryrequirement


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Membrane Transport Inhibitors

damage to the plasma membrane leads to leakage of

the cell contents and ultimately death of the cell

polymyxins

cause changes in structure of membrane

can bind to eukaryotic cells

limits the use of polymyxins to topical use


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Antimicrobial Susceptibility Testing

determines effectiveness of an antimicrobial agent to aspecific microorganism

Minimum Inhibitory Concentration (MIC)

determines the lowest concentration of an

antimicrobial agent needed to prevent growth ofthe microorganism in the lab

Tests for finding Minimum inhibitory concentration


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Antimicrobial Susceptibility Testing

Kirby-Bauer

qualitative determination of effectiveness

automated liquid diffusion

commercial modification that speeds up theprocess of determining the effectiveness of a drug

able to know in 4 hours

Kirby-Bauer


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Resistance to Antimicrobial Drugs

overuse and misuse of antimicrobial drugs

resistance is generally a result of

inactivation by microbial enzyme

prevention of reaching targetalteration of target


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Mechanisms of Resistancesome resistance is innate, some is acquired

most common methods of acquiring drug resistance

include

1. drug-inactivating enzymes (produced by the

organism)

the organism chemically modifies an

antimicrobial drug to render it ineffective


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Mechanisms of Resistance

2, alteration in target molecule

structural changes from mutation of the organism

prevents the drug from recognizing and binding to

the target

3. decreased uptake of drug

alterations in porin proteins found in the plasma

membrane can alter permeability of the membrane

may prevent some drugs from crossing the

barrier and entering the cell

Multi-resistant S. aureus


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Mechanisms of Resistance4. increased elimination

efflux pumps are the mechanisms that

bacterial cells use to eliminate harmful

compounds from the cell

an alteration that increases the

expression of the efflux pumps , can

increase the ability of a cell to eliminate

an antimicrobial drug


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Emerging Antimicrobial Resistance

some examples of increasingresistance include

vancomyvin- resistantenterococci

vancomycin is a last resort

drug for enterococciinfections

the resistance tovancomycin is coded in theplasmid, so the potential forspreading to otherorganisms is possible

methicillin-resistantStaphylococcus arueus(MRSA)

concern in hospitals


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Slowing Antimicrobial Resistance

can be minimized by

discriminating use of drugs in appropriate

concentrations and dosages

compliance of patients to follow the instructions

completely


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Antiviral Drugs

not much progress in the development of antiviraldrugs

targets for selective toxicity are difficult to find

viruses are only nucleic acid and proteinlack the structures that are successful targetsfor bacteria cells such as cell wall, plasmamembrane

role of mammalian host cell gets in the way

virus is only active while inside a host cell


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Antiviral Drugs

no broad spectrum drugs are available

best treatment for viral diseases is vaccination

recovery from a viral infection is almost totally

dependent on your immune system


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Antiviral Drugs

several antiviral drugs that are being used include

amantadine and rimantadine

block uncoating of the protein coat from the nucleic

acid acyclovir

antiherpes drug

nucleioside analog

terminates growing nucleotide chain


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Antiviral Drugs

azidothymidine (AZT)

AIDS treatment

blocks ability of reverse transcriptase to synthesize

DNA from the RNA template

mutational resistance is rapidly developed


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Antifungal Drugs

pathogens such as fungi, more closely resemble their

eukaryotic cousin, the human cell

very few drugs have been developed that can be

used systemically (orally) for fungal infections

polyene antibiotics

alter permeability of plasma membrane of the

fungus

most antifungal drugs are administered topically,

because of their low therapeutic index


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Antiprotozoan Agents

protozoa and helminths have complex life cycles

often interact with mammalian cells

antiprotozoan agents attack at certain stages of their

life cycle

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