BIOL243 L11 - Antibiotics - Clinical Uses and mechanisms of action

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  • Created by: Katherine
  • Created on: 27-04-17 18:33
What is an antibiotic?
They are substances that are selectively toxic to microorganisms. They kill or inhibit microorganisms without harming the patient.
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Who developed the first antibiotic?
Alexander Fleming - 1928
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What were the first antibiotics?
Naturally occuring bacteria or fungal products (penicillin, cephalosprin's, sulphonamides, streptomycin).
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When did chemists and microbiologists begin working to synthesis antibiotics? Give examples
Nitrofurantoin, Quinolones, anti-tuberculous drugs and most anti viral drugs are synthetic.)
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How did Fleming discover penicillin?
He left out a plate
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Where does the basis for the selective toxicity lie?
In the differences between prokaryotic (bcterial) and eukaryotic (human) cells.
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What is the structure of the prokaryote cell?
Cell wall, peptidogylcan, single supercoiled circular chromosome, cell membrane Isiite of cellular respiration), plasmid, cytoplasm, flagellum
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What does penicillin do?
It inhibits the synthesis of the cell wall
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What is selective toxicity?
When antibiotics target specific parts of a cell, e.g. the penicilln targets the peptidoglycan layer, only found in bacterial cell walls.
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Why are antibiotics which inhibit pathways or target structures which are found in human cells worse?
Because they cause side effects e.g. gentamin causeshearing loss and affects kidney function
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Antibiotics can be classified based on...
Chemical structure, spectrum of activity, mode of action ect.
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What are the common classes of antibiotics?
Beta lactams, Quinolones, Aminoglycosides, Macrolides, Tetracyclines, Glycopeptides, Sulpha antibiotics, Miscellaneous
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Give examples of Beta Lactams?
Penicillins, cephalosporin's, carbepenems, monobactams
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Give examples of Quinolones?
Ciproflaxacin
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Give examples of aminoglycosides?
Gentamicin, Streptomycin
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Give examples of Macrolides?
Erythromycin, clarithromycin
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Give examples of tetracyclines?
Tetracycline, doxycycline
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Give examples of glycopeptides?
Vancomycin and teicoplanin
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Give examples of sulpha antibiotics?
Cotrimoxazole (septrin), Trimethoprim
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Give examples of miscellaneous antibiotics?
Chloramphenicol, nitrofurantoin, rifamycins.
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What is the mechanism of action of antimicrobials?
Inhibitior of pathogen's attachment to, or recognition of, host. Inhibition of cell wall synthesis. Inhibition of protein synthesis. Disruption of cytoplasmic membrane. Inhibition of general metabolic pathway. Inhibition of DNA or RNA synthesis.
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What do Beta-lactam antibiotics share?
A common structure - a beta lactam ring
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Is penicillin broad or narrow?
Narrow
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What are the disadvantages of using a broad spectrum antibiotic? Why woukd I prefer to use a narrow spectrum?
Because if you have a bacteria that has resistance to broad spectrum antibiotic, it becomes very difficult to treat
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Why is a broad spectrum antibiotic bad?
It acts on your own healthy flora.
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What type of bacteria does penicillin work on?
Gram positive
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What is the mechanism of action of penicillins?
Cidal (kill bacteria) by binding to and detroying cell walls, resulting in bacteria death.
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What is the spectrum of activity/ clinical uses of penicillins?
Penicillin's are used to treat a wide spectrum of infections. Skin soft tissues, chest infection, pneumococcal, meningococcal and staphylococcal infections but there are major problems with resistance.
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What are the side effects of penicillins?
Allergic reactions
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A bacterial cell wall is composed of a macromolecule or peptidoglycan composed of...
NAG-NAM chains that are cross linked by peptide bridges between the NAM subunits.
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How are new NAG and NAM subunits inserted into the wall?
By enzymes, allowing the cell to grow. Normally, the other enzymes link new NAM sununits to old NAM subunits with peptide cross links
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How does penicillin effect this cell wall?
It prevents the cross linking of the bacterial cell wall - the cell wall loses it's integrity and breaks off easily -with osmosis occuring, it bursts easily.
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What does bacterio static mean?
The bacteria growth is inhibited
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What type of antibiotic is Cephalosporin?
Beta Lactam
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What is the mechanism of action of Cephalosporin?
Similar mode of action to penicillin (bactericidal) - they bind to and destroy bacterial cell wall.
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What is the spectrum and activity of Cephalosporins?
They have a broad spectrum of activity against Most Gram positive and Gram negatives. They are further classified into 1st (Cephalexin) 2nd (Cefuroxime), 3rd (cefotaxime and ceftraixone) and 4th (cefepime) generation cephalosporins.
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Which of the cephalosporin's have good gram negative activity?
3rd and 4th gen have better gram negative activity and 1st and 2nd have better gram positive activity.
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What is cphalosporin used for?
Used to treat skin soft tissue infections, urinary tract infections, chest infections, intra abdominal and central nervous system infections.
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What are the resistance mechanisms of Cephalosporins?
Beta lactamase production and altered binding site.
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What are the side effects to cephalosporins?
Allergic reactions. Do not give cephalosporins if patient has an anaphylactic reaction to penicillin.
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What is the mechanism of action of Aminoglycosides?
Binds to ribosome and prevents protein synthesis. They are bactericidal.
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What is the spectrum of activity?
Broad spectrum against mainly gram negative bacteria, such as E.coli, pseudomonas, klebsiella, proteus. They have limited activity gainst gram positive bacteria. Often used in combination with beta lactam antibiotics to treat gram positives, strep.
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What is the clinical use of Aminoglycosides?
UTIs, pyelonephritis, intra-abdominal infections, gynaecological infections, used in combination with penicillin's to treat endocardiitis.
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What is the side effect of aminoglycosides?
Their use is limited by serious side effects such as hearing loss (ototoxicity) and renal impairment (nephrotoxicity).
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What are aminoglycosides available as?
IV formulations. Levels have to be monitored stricktly to prevent side effects.
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How does resistance occur to aminoglycosides?
Results from altered binding site and efflux pump effect
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How do amnoglycosides work?
Some aminoglycosides cause change in 30S shape of Ribosome so mRNA is misread. Others block the docking site of tRNA. So bind to the 50S subunit, blocking proper mRNA movement through ribosome.
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What is the mechanism of tetracyclines?
They prevent bacterial protein synthesis and bacteriostatic rather than cidal
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What is the spectrum of activity and clinical uses?
Very broad spectrum against gram positives, some gram negatives (except psedumonas), atypical bacteria such as mycoplasma and rickettsial infections. Used to treat skin soft tissue infections.
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What is the metabolism of tetracyclines?
They are well absorbed after oral administration. Penetration is good into bone, skin, lung and kidneys. It is inactivated by the liver and excreted into feaces and urine. They bind to calcium and magnesium to form an insoluble complex.
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Due to binding with calcium and magnesium what are tetracyclines inhibited by?
Dairy produce
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What are the side effects of tetracyclines?
Should not be given to pregnant women or children because it affects skeletal development and causes teeth discolouration. They also cause photosensitivity reaction on exposure to sunlight.
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Give examples of tetracyclines?
Tetracyclines and doxycyline.
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