Anti-bacterial drugs Flashcards
(44 cards)
What is antibacterial chemotherapy?
Chemicals or substances produced by microorganisms to kill or prevent the growth of other microorganisms.
What does antibacterial chemotherapy target?
Targets bacteria that cause nonspecific infections in the body.
Many bacteria can cause the same symptoms.
Symptoms depend on the site, extent of infection and local reaction to infection.
How are bacteria categorised by Gram stain?
Gram positive bacteria is stained by Gram.
Gram negative bacteria do not take up the purple stain into their cytoplasm.
This is because they have an extra outer polysaccharide membrane that protects it against the dye, drugs and environmental effects.
What are forms of antibacterial drugs?
Bacteriostatic drugs stop the growth of bacteria.
Bactericidal drugs kills the bacteria, growth does not restart once the drug is removed.
What is the spectrum of antibacterial drugs?
Broad - affects many different types of bacteria
Narrow - affects a specific type of bacterium
What is selective toxicity?
Exploitable differences between the organism and the host cells.
Allows the drug to be toxic to the target but not toxic to the human cells.
What is the difference in selective toxicity in chemotherapy?
Antibacterial chemotherapy can easily pick out drugs that harms bacteria but leaves the human alone, due to large differences between bacteria and human cells.
But in cancer chemotherapy, differences between cancer cells and human cells are small, so less selective toxicity, more side effects.
What are the differences between bacteria and mammalian cells?
Peptidoglycan cell wall.
Plasma membrane in prokaryotes has no sterols like eukaryotes.
DNA is packaged into a single, circular chromosome.
Protein synthesis end results are very different.
Energy metabolism - prokaryotes have no mitochondria.
What are the metabolic pathways?
Class I - utilise environmental energy sources to make precursor molecules - ATP.
Class II Use precursor molecules to build amino acids, hexosamines, nucleotides necessary for class III reactions to produce peptidoglycan, proteins, DNA and RNA.
How effective are class I pathways for chemotherapy?
Class I pathways are very similar to humans, so are not good targets for antibacterial chemotherapy.
How effective are class II pathways for chemotherapy?
Class II reactions are better targets than class I as some reactions are specific to bacteria.
Or class II may have identical pathways or reactions, but may have differential sensitivity to chemicals or drugs.
How effective are class III pathways for chemotherapy?
Class III are the best targets, as they are involved in production of cell wall, proteins, RNA, DNA required for bacteria to survive.
These are quite specific to bacteria.
What is the difference in folate metabolism between bacteria and humans?
Human cells cannot produce their own folate.
Need to take up folate from the environment, so have specific transport mechanisms that allow cells to take up and use preformed folate.
Bacteria don’t have transport mechanisms to take up folate, so produce their own folate.
What is the folate metabolism pathway for bacteria?
P-aminobenzoic acid (PABA) is converted to folate by dihydrofolate synthase.
Folate is converted to tetrahydrofolate by dihydrofolate reductase.
Tetrahydrofolate is essential for DNA replication.
Therefore folate is essential for cell proliferation.
What are sulphonamides?
Sulphonamides are analogues of PABA, essential for folate synthesis.
Compete with PABA to inhibit DNA synthesis
Bacteriostatic antibiotic
How are sulphonamides antagonised?
Can be antagonised by excess PABA due to it acting as a competitive inhibitor.
Procaine is a local anaesthetic that is a PABA ester.
So in abscess removal, sulphonamides cannot be used as the procaine antagonises the sulphonamide.
How can bacteria adapt to sulphonamides?
If bacterial cells cannot produce folate, they can take up purine and pyrimidine bases from the environment - pus - to bypass the need for folic acid.
Pus contains breakdown products of tissue, and contains purine and pyrmidine.
What is trimethoprim?
Trimethoprim interferes with folate utilisation in bacteria, but doesn’t affect the same pathway in humans due to differential sensitivity.
So trimethoprim is a very efficient bacteriostatic, with very few side effects on human DNA production.
What is folate targeting in humans?
Targeting folate in humans would make it an anti-cancer or immunosuppressant drug because it is involved in DNA replication.
Methotrexate is a common immunosuppressant in humans, it does not affect bacteria.
What is penicillin?
An antibiotic that interferes with the production of the peptidoglycan cell wall in bacteria.
Developments have taken it from a narrow spectrum, acid sensitive drug to a broad spectrum, less sensitive antibiotic.
Methycillin is resistant to the enzymes bacteria uses to breakdown penicillin - penicillinase.
What antibiotics are used to prevent peptidoglycan synthesis?
Penicillins
Cephalosporins
Cycloserin
Vancomycin
Bacitracin
These are bactericidal as they cause the cell to die through interruption of the cell wall.
What is resistance to penicillin?
Bacteria can produce B-lactamases enzymes which rapidly break down penicillin.
Staphylococci
Neisseria gonorrhoea
Hemophilus
B-lactamase inhibitors - clavulonic acid - are added to antibiotics to make sure bacteria cannot break down penicillin
How else do bacteria have resistance to penicillin?
Gram negative bacteria can cause reduction of the membrane permeability of the antibiotic to the bacteria.
Methicillin resistant staphylococci (MRSA) can modify the penicillin binding sites.
What is polymixin B?
Increases the permeability of the cytoplasmic membrane.
Effective against gram- bacteria.
Side effects - kidney damage, vertigo, muscle weakness, apnoea.
