Antibacterial Flashcards
Gram positive
Simple cell wall with 50% peptidoglycan which is bound directly to cytoplasmic membrane
Gram negative
Outer membrane made of lipid bilayer, over peptidoglycan membrane, greater diffusion barrier.
Antibiotic definition
Natural substances which is made by a micro-organism and prevents/kills the growth of another
Bactericidal
Kills organisms, decrease population size
Bacteriostatic
Inhibits growth, lesser decrease in population size but no increase.
Selective Toxicity
Prevent action on non-pathogenic human microbiome and adverse side effects
Benefits of combination therapy
Less resistance, increase efficacy and synergism, broader spectrum.
Drugs which target protein synthesis
Mupirocin (pre-ribosomal stage inhibition). Oxazolidinones, Tetracyclines, Aminoglycosides, Chloramphenicol, Macrolides (Ribosomal inhibitors) and Fusidic Acid
Selective Toxicity of protein synthesis targeting antibacterials
Ribosomal size is different between mammals and bacteria. Enzyme which Mupirocin acts on is different and lower affinity for mammal one, Uptake of tetracyclines and fusidic acid is not as good in mammalian cells. Can get ADR from interaction with mitochondrial synthesis
Mupirocin mode of action
Competitive inhibitor for isoleucyl tRNA synthetase, enzyme which links tRNA amino acids together. No raw materials to create polypeptide chain at ribosomes. Bacteriostatic
Clinical Use of Mupirocin
Only topical as rapidly hydrolysed when ingested. Only against Gram positive. Staphylococcal or streptococcal skin infections, stop nasal carriage of MRSA in hospital patients & staff.
Oxazolidinones
Bind to 50S subunit and prevent correct positioning of aminoacyl-tRNA and blocks entry of subsequent molecules. Bacteriostatic
Examples of Oxazolidinoes
Linezolid or Tedizolid (more recent, less ADR and mylosuppression, more ABx activity). All are fully synthetic
Clinical use of Oxazolidinones
Gram positive only, unable to get high intracellular cones of gram negative. Skin and soft tissue infections and Hospital acquired pneumonia. IV ORAL
ADR of oxazolidinoes
Reversible thrombocytopenia and anaemia from myelosuppression. Mild LFT abnormalities
Tetracycline action
Bind to 30S subunit via hydrogen bonds. Prevents associated of aminoacyl- tRNA with the ribosome. Lipophilic tetracyclines more active than hydrophilic.
Clinical use of tetracyclines
broad spec, Oral, IV or topical.Chlamydia, mycoplasma pneumonia, cholera, Lyme disease,
Rocky Mountain spotted fever
Examples of tetracyclines
New = tigecyclin IV only. Doxycycline, tetracycline
ADR of tetracyclines
Due to ability to chelate metal ions CI in young children and late-pregnant woman and deposits in bone and teeth. Photosensitivity.
Aminoglycosides action
Bactericidal. Bind to 30S or both subunits mRNA misreading causes abnormal proteins to be synthesised. Hydrophobic regions burrow into membrane, destabilising it and contents leak/lyse.
Clinical use of aminoglycosides
IM or IV. Montherapy in severe sepsis (particular causative agents), plague, enterococcal endocarditis. Combo therapy for gram positive TB or anaerobic infections
Examples of aminoglycosides
Polycationic with 2 sugars enclosing 3rd ring structure. streptomycin, gentamicin, neomycin.
ADR of aminoglycosides
Not great selective toxicity. Ototoxicity, Nephrotoxicity, Neuromuscular blockade.
Chloramphenicol Action
Binds to 50S subunit and inhibits the enzyme responsible for amino acid chain elongation - peptidyl transferase.
Chlorampenicol clinical aspects
BROAD-SPEC bu toxicity restricts use. Oral, IV or topical. Typhoid and paratyphoid due to Salmonella infections
ADR of chlorampenicol
Myelosuppression and Gray Syndrome (in the very young - life threatening)