Antibacterial drugs Flashcards
What does antimicrobial mean?
Chemical which inhibits the growth of microorganisms.
What is a broad spectrum antibiotic?
Antibiotic against a large bacterial genera. This is useful for polymicrobial infection and based on empirical usage (experience), has past benefits.
What is a narrow spectrum antibiotic?
Antibiotic against a limited bacterial genera such as gram positive or negative.
What connects the lipoglycan cell wall to the peptidoglycan layer?
Lipoproteins
What are the anti-bacterial properties?
Selective toxicity, bactericidal, slow emergence of resistance bacteria and have a narrow spectrum of activity.
What is bactericidal?
Kills bacteria
What is bacteriostatic?
Inhibits growth of bacteria
What is selective toxicity?
Avoid harming the host
How do antibiotics affect bacteria?
Target cell wall synthesis and cyptoplasmic membrane, metabolites for DNA synthesis, inhibiting protein synthesis/translation and nucleic acid synthesis
What is a beta lactam?
Antibiotic with a beta-lactam in their structure
What are the beta lactam antibiotics?
Penicillin, cephalosporin and glycopeptides which inhibit celll wall synthesis
How do cephalosporins work?
Cefuroxime is an cephalosporin which inhibits the transpeptidase enzyme penicillin binding proteins. It is well-tolerated and safe for breastfeeding.
What are the targets of glycopeptide antibiotics?
Vancomycin binds to the cell wall unit precursors in the cyptoplasm and blocks linkage with lipid for delivery. Beta lactam antibiotics can only target gram positive bacteria because it cannot cross the lipopolysaccharide cell wall in gram negative.
What is penicillin binding proteins?
Membrane associated proteins.enzyme involved in the formation of peptidoglycan cell wall which polymerise the bond between lysine and alaine via transpeptidasation.
How does the peptidoglycan form?
Peptidoglycan monomers are formed in the cyptoplasm and cross linked to bind to the lipid bactoprenol for delivery to existing peptidoglycan cell wall. It uses transpeptidation via transpeptidase enzymes penicllin binding proteins to form a link and create a mesh and reform the links.
What is the target of beta lactams excluding glycopeptides?
Inhibits the transpeptidase enzyme penicillin binding proteins for cross linking of peptidoglycan monomers to existing peptidoglycan membrane which inhibit cell wall synthesis.
What are the ribosomes for prokaryotes?
70s ribosomes with small 30s subunit and large 50s subunit
What are the ribosomes for eukaryotes?
80s ribosome with 40s small subunit and large 60s subunit.
Which drugs inhibit the small subunit of prokaryotes?
30s small subunit inhibited by aminoglycosides (gentamycine)and tetracyclins (oxatetracycline))
What is the effect of aminoglycosides?
Gentamycin is bactericidal by binding to 30s small ribosomal subunit on 16s ribosomal RNA
What is the target of tetracycline?
Oxatetracycline targets the 30s small ribosomal subunit on prokaryote ribosome. It can target eukaryotic ribosomes but has greater affinity for prokaryotic.
Which drugs target the large subunit of prokaryote ribosomes?
50s subunit by chloramphenicol, the macrolide (erythromycin)
Which protein is important for tRNA and mRNA movement?
Efg- g elongation factor which uses the enerngy stored in GTP for this process during translation
Which drug inhibits Efg-g elongation factor?
Fusidic acidic, which is given for skin infections like impetigo caused by staphylococcal infections.
Fusidic acid may interfere with bilirubin metabolism.
Which drugs inhibit DNA replciation?
Quinolones (ciprofloxacin) and rifamycin
What is the action of quinolones?
Ciprofloxacin inhibits DNA gyrase (AKA toposiomerase II) for DNA replication via supercoiling. It is a G2 phase inhibitor used in cancer treatment.
What is the action of rifampicin?
Blocks RNA synthesis directly by blocking RNA polymerase and protein synthesis indirectly. It inhibits liver enzymes for drug clearance.
How are nucleic acids synthesised?
PABA and pteridine substrates -> dihydrofolic acid ->dihydrofolate -> tetrahydrofolate
What drug inhibits PABA?
Sulfonamide such as sulfamethoxazole- it is a competitive inhibitor of PABA which has selective toxicity because humans need to take up folic acid
Which drug inhibits dihydrofolate reductase?
Trimethoprim which is a structural analog of folic acid. It has a higher affinity for bacterial dihydrofolate reductase than human bacterial dihydrofolate reductase.
What are polymyxins?
Antibiotic which acts as a membrane detergent by disrupting the hydrophobic-hydrophilic bonds. It is a broad spectrum antibiotic used for multi-drug resistant gram negative bacteria.
What is a polymyxin antibiotic?
Colitisin which is bactericidal antibiotic for multi-drug resistant bacteria. Should be avoided in myasthenia gravis, and avoided in asthma.
What is the narrow spectrum peniccilin?
Benzylpenicillin
What is the broad spectrum penicillin?
Amoxocillin
What is resistance?
Sensitivity of a bacterial isolate to an antibiotic at a certain concentration
What are the classifications of resistance?
Resistant, intermediate and sensitive
What is minimum inhibitory concentration?
Minimum concentration of the antibacterial agent in which bacterial growth is not inihibited.
How does antibiotic resistance occur?
Modifiying antibiotic target such as active site shape
Limiting access of antibiotic to target such as reducing penetration
High efflux
Enymatic inactivation of antibiotic via cleavage
This can lead to multi-drug resistance.
What are the types of resistance?
Innate resistance where it is impermeable to the drug and lacks a suitable target. Acquired resistance occurs due to horizontal gene transfer or mutations. Biofilm growth also allows bacteria to develop resistance.
What is biofilm growth?
Bacteria irreversibly attach to extracellular surface and produce extracellular polysaccharides, creating a biofilm. This creates a physical barrier to antibiotics and slow the growth rate of bacteria for detection.
How does resistance to beta-lactams occur?
Produe and secrete beta-lactamase enzyme to degrade the beta-lactam antibitoic. Alternatively, bacteria may alter the penicllin binding protein so beta-lactam cannot interact with it
How does resistance to antibiotic occur?
Horizontal gene transfer and mutations in native genes or regulatory genes
Why are resistant isolates a growing issue?
Resistant isolates have increased in number and spread amongst the population
Which drug blocks beta-lactam?
Ceftazidime/avibactam
How can antibiotics be prescribed effectively?
Selecting shortest course of antibiotics, avoid broadp spectrum agents, provide immediately to patient with life-threatening infection.
What type of bacteria is the target of glycopeptides?
Gram positive only
Tetracycline
Causes photosensitivity
Ciprofloxacin side effects
Elongation Of QT a interval and peripheral neuropathy and anaemia, thrombocytopenia
Cephalosporin
Beta-lactam antibiotic which inhibits cell wall synthesis
Antibiotics contraindicated in under 12
Tetracyclines
Innate antibiotic resistance
Resistance due to the functional or structural characteristics of the antibiotic which means it would never be effective
Acquired antibiotic resistance
Resistance due to mutations of the bacteria
Rifampicin considerations
Inhibits cytochrome P450, increasing drug availability.
