Lecture 7 = Antibiotics

Question 1

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

Answer 1

44 years

pneumonia, tuberculosis, infection

Question 2

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

Answer 2

82 years

heart disease, cancer, stroke

Question 3

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

Answer 3

originally infection

now wear/tear

Question 4

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

Answer 4

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

Question 5

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

Answer 5

miasma = disease from bad smells (special mask)

curse from god = sacrifice people

spontaneous generation

Question 6

describe germ theory of disease

Answer 6

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

Question 7

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

Answer 7

disproved miasma theory

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

Question 8

what contribution did John Snow have on cholera?

Answer 8

created a map of cases of cholera

linked cholera outbreak with water pump near a cess pit

took off handle and outbreak stopped

Question 9

describe discovery of pasteurization

Answer 9

Louis Paster (1864)

involved heating milk to kill bacteria and then letting it cool

made milk last longer and be safer to drink

Question 10

who developed antisepsis?

Answer 10

Lister (1867)

Question 11

describe the discovery of gram-stained bacteria

Answer 11

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

Question 12

describe Magic Bullet theory

Answer 12

Paul Erlich wanted to discovery a magic bullet

something that would target harmful bacteria and ignore everything else

Question 13

describe Trypan Red discovery

Answer 13

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

Question 14

describe Salvarsan 606 discovery

Answer 14

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

Question 15

what were the benefits of Salvarsan 606

Answer 15

first effective treatment against syphilis

good for smallpox

reduced deaths for both smallpox/syphilis

first ever antibiotic

Question 16

what were the disadvantages of Salvarsan 606

Answer 16

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

Question 17

describe the discovery of Prontosil

Answer 17

Gerhard Domagk (1932)

first commercially successful antibiotic

developed by experimenting with dyes

gave to daughter with throat infection and cured

Question 18

describe in-vivo nature of Prontosil

Answer 18

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

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

Question 19

what is the prodrug and active ingredient in prontosil

Answer 19

prontosil = prodrug

sulfanilamide = active ingredient

Question 20

why did researchers shift from use of prontosil to sulphanilamide?

Answer 20

prontosil was red dye and could change skin colour

sulphanilamide was colourless

Question 21

what was the first sulfa drug?

Answer 21

sulfanilamide (1932)

Question 22

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

Answer 22

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

Question 23

describe initial discovery of penicillin

Answer 23

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

Question 24

describe Florey and Chain discovery of penicillin

Answer 24

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

Question 25

describe how penicillin came to US

Answer 25

wartime in England - scared of lab getting bombed

pharmaceutical companies increased penicillin production

Question 26

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

Answer 26

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

Question 27

when did penicillin become available to public?

Answer 27

1945

Question 28

describe structure of bacterial cells

Answer 28

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

Question 29

describe structure of human cells

Answer 29

consists of cell membrane and no cell wall
very large

Question 30

describe importance of cell wall in bacteria

Answer 30

very small in size with lots of internal pressure from high concentration of inner materials

cell wall holds cell together

Question 31

describe why human cells don’t need cell wall

Answer 31

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

Question 32

how does penicillin work

Answer 32

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

Question 33

why does penicillin only work on bacteria?

Answer 33

because penicillin only targets the enzyme that builds cell walls

we don’t naturally have these enzymes in body

Question 34

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

Answer 34

penicillin G

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

Question 35

benefits of artificial penicillin

Answer 35

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

Question 36

how are artificial penicillins made

Answer 36

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

Question 37

what is the major side effect of penicillin? why?

Answer 37

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

Question 38

what is cephalosporin

Answer 38

antibiotic fungus found in Italian sewer

Question 39

where was streptomycin found

Answer 39

in throats of chickens

Question 40

when was the Golden Age of antibiotics

Answer 40

1940s to 1950s

no new antibiotic families found since 1997

Question 41

what can lead to antibiotics resistance

Answer 41

over-prescription
prophylactic in cattle
patient non-compliance

Question 42

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

Answer 42

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

Question 43

why is patient compliance a problem for antibiotic resistance?

Answer 43

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)

Question 44

describe the process of bacterial resistance

Answer 44

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

Question 45

what is necrotizing fasciitis

Answer 45

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

Question 46

what is clostridium difficile

Answer 46

causes large infection of intestine

hard to get rid of

Question 47

why are doctors reluctant to prescribe new antibiotics

Answer 47

will use old drugs first

want to make sure that bacteria don’t get resistant to new drugs