Lecture 7 = Antibiotics Flashcards by Kate Bastodkar

describe life expectancy in 1900s (years and causes of death)

44 years

pneumonia, tuberculosis, infection

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describe life expectancy in 2004 (years and causes of death)

82 years

heart disease, cancer, stroke

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what was the original cause of death and what is it now?

originally infection

now wear/tear

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why were people unable to be treated for disease in early times?

people didn’t know the cause of disease, so didn’t know how to treat it

people would make up treatments just to get money

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what were some early beliefs of causes of disease? and how would people protect themselves?

miasma = disease from bad smells (special mask)

curse from god = sacrifice people

spontaneous generation

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describe germ theory of disease

Agostino Bassi (1844)

states that disease is caused by microscopic organisms that you can’t see

organisms essentially eat you and cause disease as result

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what theory did John Snow disprove + what theory did he come up with?

disproved miasma theory

came up with epidemiology = study of populations and how diseases spread within them

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what contribution did John Snow have on cholera?

created a map of cases of cholera

linked cholera outbreak with water pump near a cess pit

took off handle and outbreak stopped

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describe discovery of pasteurization

Louis Paster (1864)

involved heating milk to kill bacteria and then letting it cool

made milk last longer and be safer to drink

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who developed antisepsis?

Lister (1867)

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describe the discovery of gram-stained bacteria

discovered by HC Gram (1884)

involves staining bacteria by administering dyes

different bacteria with different properties allow them to selectively uptake dyes

allows for identification of gram positive vs. gram negative bacteria

start of discovery of antibiotics

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describe Magic Bullet theory

Paul Erlich wanted to discovery a magic bullet

something that would target harmful bacteria and ignore everything else

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describe Trypan Red discovery

Paul Erlich (1907)

performed experiment using Trypan red dye and trypanosome cells

noticed that there were certain chemicals in trypanosome cells that were not in regular blood cells that allowed them to pick up dye

led to discovery of Salvarsan 606

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describe Salvarsan 606 discovery

Paul Erlich (1907)

based on Trypan red discovery

chemically altered structure of dye by replacing to N’s in centre with arsenic (same column of periodic table = same properties, but poison)

became first ever antibiotic = a selective poison to selectively target cells

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what were the benefits of Salvarsan 606

first effective treatment against syphilis

good for smallpox

reduced deaths for both smallpox/syphilis

first ever antibiotic

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what were the disadvantages of Salvarsan 606

not drug like

treatment required several months

many injections + large injection volumes

had to do injection for 1-2 hours (because IV’s weren’t invented) - dangerous + could result in amputation of limb

highly toxic

not successful

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describe the discovery of Prontosil

Gerhard Domagk (1932)

first commercially successful antibiotic

developed by experimenting with dyes

gave to daughter with throat infection and cured

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describe in-vivo nature of Prontosil

only works in-vivo (not cultures) + is prodrug

undergoes metabolism in the liver and gets turned into active ingredient = sulphanilamide

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what is the prodrug and active ingredient in prontosil

prontosil = prodrug

sulfanilamide = active ingredient

why did researchers shift from use of prontosil to sulphanilamide?

prontosil was red dye and could change skin colour

sulphanilamide was colourless

what was the first sulfa drug?

sulfanilamide (1932)

how do sulfa drugs work? why do you need a strong immune system?

inhibit bacterial growth - so you need a strong immune system to fight off remaining bacteria

works by blocking the enzyme that contributes towards producing bacteria

mimics the natural substrate - has a similar structure that binds to the receptor preventing the actual substrate from binding so normal reaction won’t occur and bacterial growth will be inhibited

describe initial discovery of penicillin

Alexander Fleming (1928)

accidentally contaminated plate with penicillin mold

noticed that mold killed 1/2 types of bacteria on plate

published findings but didn’t think anything of it, and used mold as way to purify and grow bacteria instead

describe Florey and Chain discovery of penicillin

1941

found Fleming’s research paper and tried to grow/isolate penicillin

very difficult because very little penicillin can be isolated from mold (1000kg of mold for 1g penicillin)

originally grown in milk bottles

published experiment in mice - group given penicillin survived

also gave to police officer with infection - reduced symptoms but didn’t survive because not enough was available

describe how penicillin came to US

wartime in England - scared of lab getting bombed pharmaceutical companies increased penicillin production

what was main issue with production of penicillin and how was it solved?

mold didn't produce a lot of penicillin - was inconvenient to grow because required a lot of oxygen originally grown in trays with layer of milk and large surface area started growing penicillin in large tank pumped with oxygen Peoria, Illinois because penicillin capital - originally big beer place, but beer brewing equipment was used to develop penicillin instead

when did penicillin become available to public?

1945

describe structure of bacterial cells

consists of bacterial cell membrane and cell wall very small in size

describe structure of human cells

consists of cell membrane and no cell wall very large

describe importance of cell wall in bacteria

very small in size with lots of internal pressure from high concentration of inner materials cell wall holds cell together

describe why human cells don't need cell wall

very large in size so able to contain internal pressure without cell wall

how does penicillin work

prevents synthesis of bacterial cell walls causing them to explode b-lactam binds to enzyme responsible for cell wall synthesis, and permanently altering structure bacteria can no longer make cell walls and explode

why does penicillin only work on bacteria?

because penicillin only targets the enzyme that builds cell walls we don't naturally have these enzymes in body

what is the natural version of penicillin? why isn't it drug-like?

penicillin G unstable must be injected extracted from mold only works against certain types of bacteria

benefits of artificial penicillin

can be made via semi-synthesis can be stored for longer works against most bacteria can be taken orally

how are artificial penicillins made

through semi-synthesis take natural penicillin from mold (penicillin G) extract core structure through chemical reactions do more chemical reactions/add stuff to make artificial drug

what is the major side effect of penicillin? why?

allergy some people have substances in body that penicillin can interact with/bind to when penicillin binds to these substances, body recognizes as foreign material which triggers allergic reaction

what is cephalosporin

antibiotic fungus found in Italian sewer

where was streptomycin found

in throats of chickens

when was the Golden Age of antibiotics

1940s to 1950s no new antibiotic families found since 1997

what can lead to antibiotics resistance

over-prescription prophylactic in cattle patient non-compliance

what is prophylactic and why is it a problem for resistance?

antibiotic used in cattle feed as preventative measure to prevent cows from getting sick promotes resistance in bacteria that live in animals this resistance can be transmitted to human bacteria

why is patient compliance a problem for antibiotic resistance?

people skip doses/don't take correctly - which promotes resistance need a certain amount of penicillin in blood to be effective + takes time to circulate (can be effected if instructions aren't followed correctly)

describe the process of bacterial resistance

some bacteria are weaker/stronger than others weaker bacteria gets killed first if strong bacteria survive (due to non-compliance), a newer/tougher population will be created this process can be repeated over and over (several generations of new bacteria created) causing a resistance to the antibiotic therefore, important to continue taking antibiotic until all bacteria are killed

what is necrotizing fasciitis

caused by staphylococcus aureus flesh eating virus bacteria makes wall against antibiotics - must be killed with debridement make incision to scrape out infection and administer special antibiotics limb usually amputated

what is clostridium difficile

causes large infection of intestine hard to get rid of

why are doctors reluctant to prescribe new antibiotics

will use old drugs first want to make sure that bacteria don't get resistant to new drugs