Antibiotics Flashcards

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1
Q

Uses of antibiotics

A
  • Drugs used to treat bacterial infections
  • Widely used and misused drugs
  • In hospitals, they acquire 30% of the drug budget
  • 80% of human use in the community:
    • > 50% is for respiratory infections
    • > 15% is for urinary tract infections
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2
Q

What are antibiotics?

A
  • Natural products: fungi and bacteria that live in the soil dwellers.
  • These organisms are used to coexisting with other microorganisms, so they developed mechanisms which produce compounds that inhibit the growth of other microorganisms.
  • Able to collect these products by fermentation and then chemically modify them, so they are more suitable for pharmacological properties.
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3
Q

How are scientists able to get antibiotics? What do they do to antibiotics?

A

Scientists are able to collect these products by fermentation and then chemically modify them, so they are more suitable for pharmacological use:

  • They increase their pharmacological properties
  • They increase their antimicrobial effect
  • Need to make sure they are not toxic, not metabolised too quickly and doesn’t bind protein in the blood so it can be free in the blood - this reduces the dose.
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4
Q

Example of synthetic antibiotics

A

Most antibiotics are derived from natural products, some are totally synthetic such as sulphonamides

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5
Q

Discovery of antibiotic penicilin

A
  • Alexander Fleming’s original culture of Staphylococcus aureus was contaminated with penicillium notatum
  • Diffusion of the penicillin into agar caused lysis of the bacteria
  • This lead to the discovery of the antibiotic penicillin
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6
Q

Priniciples of antibiotics as therapeutic agents

A
  • Selective toxicity

- Therapeutic margin

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7
Q

Selective toxicity of antibiotics

A
  • This means the antibiotic should be able to kill the bacteria without harming the host cells.
  • This is able to happen because bacteria and human cells have different structures, an antibiotic can be made to target the cell wall of a bacteria so not to harm the host.
  • More difficult in anti-viral because viruses are intracellular hosts which means they integrate within the human genome.
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8
Q

Therapeutic margin of antibiotics

A
  • This is the balance of the antibiotic between being sufficient at treating the bacterial infection and becoming toxic to the host.
  • It is the active dose which is the MIC (minimum inhibitory concentration) which is the concentration needed to see an active effect of the drug.
  • Some antibiotics are safe so you can increase the dose by a lot and no toxic effect will be seen, however some antibiotics are very toxic so the MIC and toxic dose are very close.
  • When a drug is described as being safe it means, they have a wide therapeutic effect and vice versa.
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9
Q

How do antibiotics disturb the natural flora?

A
  • The natural flora is maintained because each microbe keeps the other one in balance by producing something that inhibits the growth of another.
  • e.g. in the gut - when the balance is disturbed, this is when disease occurs because one microbe grows to form colonies.
  • For example Clindamycine and broad spectrum beta lactams are used leading to the overgrowth of C. dif which is a gram +ve spore forming bacteria, leading to diarrhoea, ulceration and inflammation.
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10
Q

How are antibiotics classified?

A
  • By type of activity
  • Structure
  • Target site of activity
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11
Q

What are the types activity of antibiotics?

A

Used in different scenarios -

  • Bacteriostatic: inhibit the bacteria from growing e.g. when a patient is not immunocompromised and there not used for emergency use. Need a higher dose to be able to kill the bacteria (toxic dose)
  • Bacteriocidic: actively kills the bacteria e.g. used when a patient is immunocompromised and therefore can be used for emergency, the MIC and the toxic dose are very close and therefore it can be used to kill the bacteria.
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12
Q

How does the structure of antibiotics effect?

A
  • Some antibiotics have specific structures, which help them target the bacteria they are killing
  • E.g. beta lactams antibiotics have a beta lactam ring in their structure which means they are able to act as competitive substrates for the enzymes involved in the bacterial cell wall.
  • Therefore, when a bacteria is resistance, it means they have enzymes which are able to breakdown the beta lactam ring in the antibiotic so it no longer has a therapeutic effect.
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13
Q

Broad specturm antibiotics

A

Able to work on multiple different bacteria and overuse of this means resistance can occur

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14
Q

Narrow spectrum

A
  • Antibiotics that can only work on certain bacteria and therefore need to know what bacterial infection it is to administer the drug.
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15
Q

Cephalosporins

A

Generation of modified antibiotics each with a different chemical modification which is suited to certain types of bacteria
The modification target different types of bacteria, due to different types of bacteria having different structures

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16
Q

What are the 6 types of bacterial targets for current antibiotics?

A
  • Cell wall synthesis inhibitors
  • Protein synthesis inhibitors
  • DNA/RNA synthesis inhibitors
  • Folic acid metabolism inhibitors
  • Cell membrane damaging
  • Free radicals generators
17
Q

Cell wall synthesis inhibitors include examples

A
  • Beta lactams and vancomycin

- Inhibit the cell wall formation which means bacteria will die and cleared off by the immune system

18
Q

Protein synthesis inhibitors include examples

A

Erythymocyin and Chloamephicnal

  • Bind to the ribososome in different places and inhibit protein synthesis.
  • Does damage the host protein synthesis because there is different in the bacterial ribosomes and the host ribosomes
19
Q

DNA/RNA synthesis inhibitors

A

Rifamocin and Quinolone

  • Inhibit certain enzymes which are only specific to the bacteria:
    • > DNA gyrase which is needed for coiling and uncoiling when the genome is the replicating
    • > DNA directed RNA polymerase which inhibits RNA making
  • This type of antibiotics is used to stop the spread of community acquired meningitis and TB
20
Q

Folic acid metabolism inhibitors

A

Trimetrhoprim and Sulfoamides

  • Folic acid is a co-factor for enzymes which are essential in both bacteria and host, however, host doesn’t synthesise folic acid in the body, it is consumed whereas bacteria synthesises it.
  • Therefore, these antibiotics inhibit the bacteria from making folic acid meaning they are not able to function properly which means they die.
  • These also have good selective toxicity
21
Q

Cell membrane damaging

A

Colistin

  • Most toxic to the host because both the bacteria and the host have cell membranes.
  • Only used on bacteria which is resistant to other antibiotics such as gram -ve E. coli
22
Q

Free radical generators

A

Nitrofurantoin

  • Free radicals are toxic in the bacteria and therefore anaerobic bacteria are usually treated with this.
  • Typically used to treat UTI because it is not toxic and most of the drug goes to the kidney which is the site of infection.
23
Q

Gram +ve bacteria

A
  • Contain a large peptidoglycan: cross-linking structure that sits on the top of the membrane and contains components of the bacteria cell wall.
  • Antibiotics that target the cell wall synthesis work on enzymes which are involved in making the peptidoglycan
  • These are present in the area between the membrane the peptidoglycan which is a highly porous structure and therefore the antibiotics can easily access this area.
24
Q

Gram -ve bacteria

A
  • Contains inner membrane, periplasmic space containing peptidoglycan and outer membrane
  • Outer membrane is very impermeable and requires pores for the antibiotic to cross the periplasmic space.
  • It is easier to treat gram +ve bacteria compared to gram -ve bacteria.
25
Q

Structure of peptidoglycan

A
  • made of pentapeptides which are cross linked together.
  • They hold the matrix together which has a long polysaccharide chain
  • This is put together by a series of enzymes
  • Different bacteria have different peptidoglycan and therefore not all antibiotics will work on all bacteria.
26
Q

How to synthesise peptidoglycan?

A

Need: 2 disaccharides and 5 peptides, the last 2 peptide are D-ala.

  1. D-ala molecule is transported across the membrane by linking a lipid transport molecule.
  2. Once it crosses the membrane, it gets attached to a 5 amino acid by enzymes which remove the D-ala D-ala sequence, leading to the structure being polymerised to the cell wall.
  3. The transcarboxypeptidase enzyme which is found in the bacteria cell wall does that.
27
Q

How do beta lactams work in gram +ve bacteria?

A
  • Work on the enzyme - transcarboxypeptidase enzyme that makes the peptidoglycan and affects the cross-linking structure.
  • Vancomyocin is able to attach to the terminal D-ala which means the enzyme does not cleave off.
28
Q

How do beta lactams work on Gram -ve bacteria?

A
  • In the Gram -ve bacteria, the porin is needed to allow the beta lactam in through the outer membrane.
  • Once it binds to the penicillin binding proteins (PBP) which are enzymes responsible for making the peptidoglycans; it inhibits the binding proteins meaning the cross-linking molecules are not able to occur and the wall is not formed.
  • This triggers autolysis of the bacteria and hence why beta lactams are bactericides
29
Q

Action of sulphonamide

A

Blocks the enzyme competing with the natural substrate PABA.
This means the bacteria cannot make folic acid and dies.

30
Q

When are antibiotics used?

A
  • treatment for bacterial infection
  • Prophylaxis which means they prevent someone from getting the infection:
    • > This can be due to someone coming in contact with an infected person.
    • > Peri-operative gut surgery
    • > People who are immunocompromised
31
Q

What does the minimum inhibitory concentration (MIC) depend on?

A
  • Host: age, weight, severity of infection, liver and kidney function
  • Bacteria: susceptibility of the organism
  • Antibiotic properties: toxicity