Download Antibacterial Drugs (SL + HL)

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Medicines and Drugs 6
Antibacterial Drugs (SL + HL)
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D6 Antibacterials - Assessment Statements
D.6.1
Outline the historical development of penicillins.
D.6.2
Explain how penicillins work and discuss the effects of
modifying the side-chain.
Also see D.8.3 (HL students).
D.6.3
Discuss and explain the importance of patient
compliance and the effect of penicillin
overprescription.
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Bacteria - Background
Some Pathogenic Bacteria
Neissera gonorrhea
Staphylococcus
Vibrio cholerae
Salmonella
Syphilis
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Bacteria - Background
Bacterial Structure
There are many types of bacteria, with varying structures.
These features are common to most bacteria:
unicellular
target of many antibiotics
!
http://geneticssuite.net/node/11
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Bacteria - Background
Mode of Action of Pathogenic Bacteria
bacteria release
chemicals called toxins
into the blood and
tissues
toxins act on different target organs
to disrupt cell processes
e.g. tetanus (lockjaw) and Salmonella
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Antibacterials
aka antibiotics
inhibit the growth of bacteria
http://www.accessexcellence.org/AE/AEC/CC/s1.php
specifically inhibit
bacterial cell growth
and not human cell
growth
Attack!
✗
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Antibacterials
Early Antibiotics
sulfonamides
the first
antibacterial drugs
“sulfa drugs”
used in the dye industry
effective treatment of septicemia
from early 1930s
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Antibacterials
“Modern” Common Antibiotics
naturally produced by certain molds
now synthesized in laboratories
penicillin G and penicillin V
ampicillin
amoxycillin
tetracycline
erythromycin
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Discovery and Development of Penicillin
The Discovery!
one of the greatest revolutions in medicine
Alexander Fleming
Scottish microbiologist and WWI veteran
studied the infectious bacterium
Staphylococcus aureus in 1928 in London
http://en.wikipedia.org/wiki/Alexander_Fleming
noticed many of the culture plates
became contaminated with mold
and was ready to throw them away
!
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Discovery and Development of Penicillin
The Discovery!
serendipity
closer observation revealed that there
was a clear zone around the mold
no bacteria grew near the mold
Fleming concluded that something
produced by the mold inhibited
bacterial growth.
mold =
Penicillim
notatum
!
published a paper
and then stopped
could not isolate the active compound
Chemistry fail?
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Discovery and Development of Penicillin
Development of the Drug
!
1940 ... enter Florey and Chain
We know
Chemistry!
worked at Oxford to isolate the
active ingredient from the
Penicillin notatum mold
injected the isolated
compound into infected mice
high survival rate
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Discovery and Development of Penicillin
Development of the Drug
WW II
need for a drug to combat
battle wounds
further drug development
moved to the US
large batch production of
penicillin in corn-steep liquor in
fermentation tanks
1945 Nobel Prize in Medicine awarded
to Fleming, Florey and Chain
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How Penicillin Works
General Structure of Penicillin
There are several types of “penicillin” extracted from the Penicillin notatum mold.
They all have this basic structure:
!
Identify four structural features.
carboxyl group
2º amide
beta lactam ring
R group
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How Penicillin Works
Different Penicillin Structures
There are several types of “penicillin” extracted from the Penicillin notatum mold.
!
penicillin V
R GROUP
!
amoxicillin
!
penicillin G
!
ampicillin
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How Penicillin Works
Different Penicillin Structures
What is the effect of changing the R-group?
1. no change to the beta lactam ring
The beta lactam ring is responsible for the activity of penicillin.
2. it may change the properties of the drug
Penicillin G is broken down by the stomach.
How must it be administered?
Penicillin V is not broken down by the stomach.
How must it be administered?
3. it may improve the resistance of the drug
Ampicillin is not as likely as penicillin G or V to be broken down
by the enzymes in some bacterial strains.
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How Penicillin Works
Mechanism of Action
penicillin blocks the synthesis of
peptidoglycan (a component of
the bacterial cell wall)
The cell wall is weakened.
Water can move into the cell and the
bacterium lyses and dies.
Penicillin is a bacteriocidal antibiotic.
Penicillin does not attack human cells because human cells do not have
cell walls (i.e. no peptidoglycan)
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Antibiotic Use, Overuse and Misuse
Antibiotics ONLY act against bacteria ... NOT viruses.
1. antibiotics are over-prescribed
may kill the helpful bacteria in your
intestinal tract
harmful bacteria may replace them
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Antibiotic Use, Overuse and Misuse
2. patients do not follow the complete course of treatment
= noncompliance
some harmful bacteria survive
contributes to development of resistance
3. antibiotics are available in some parts of the world without a
prescription
people self medicate
leads to overuse & development of resistance
4. wide use of antibiotics in feedstock
70 - 80% of all antibiotic use
enters food products
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Antibiotic Resistance
Some bacteria have an enzyme called penicillinase.
breaks down pe
n
icillin
bacteria are resistant to the antibiotic
Chemists try to develop new antibiotics which are not broken down by
bacterial enzymes.
modify the R group
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Antibiotic Resistance
natural selection
When a bacterial population is exposed to the antibiotic over a long period of time,
the ones without resistance die. However, if there are resistant bacteria, they survive
and reproduce. Over long periods of time, the remaining bacteria will now be
resistant. They cannot be treated with the original antibiotic, and new antibiotics must
be used (or developed).
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