Antibiotic Chemistry Flashcards
What are the different mechanisms of action for antibiotics?
Inhibition of bacterial cell wall synthesis
Inhibition of protein synthesis
Inhibition of nucleic acid transcription + replication
Injury to plasma membrane
Inhibition of synthesis of metabolites
What is the difference between gram + and gram - bacteria?
Gram -:
Very thick and lipophilic membrane
Periplasmic space
Which antibiotics inhibit bacterial cell wall synthesis?
Beta lactams
What are beta lactam’s structure?
R group
Beta lactam ring = planar
Carboxylic acid
How do beta lactams inhibit bacterial cell wall synthesis?
For covalent body
Formation of salt bridge
Blocks H2O + peptide chain
What are the beta lactam adverse reactions?
Anaphylaxis
Urticaria
Steven-Johnson syndrome
Acute exanthematic pustulosis
What do beta lactams interact with?
Penems + valproic acid
Methotrexate
Warfarin
What is beta lactam resistance?
Provides another nucleophilic residue to break up ring + inactivate antibiotic
What does MRSA do?
Produces mutated penicillin binding protein
= methicillin doesn’t bind as efficiently
What are some beta lactamase inhibitors?
Co-amoxiclav = amoxicillin + clavulanic acid
Tazocin = piperacillin + tazobactam
What do glycopeptides do?
Inhibition of bacterial cell wall synthesis
What is an example of glycopeptide?
Vancomycin
= used to treat MRSA
Bactericidal
Describe structure of vancomycin
Fixed conformation of hexapeptide
Forms H bonding
D-ala-D-ala held in deep cleft
How does vancomycin inhibit bacterial cell wall synthesis?
Dimerization can take place
Head to tail
4 H bonds
Steric shield to transglycosidase + transpeptidase enzymes
What is teichoplanin?
Glycopeptide
Treat gram +
Bactericidal
What are the adverse reactions to glycopeptides?
Anaphylaxis
Hypotension
Red man syndrome
How does vancomycin resistance happen?
Modification of cell wall precursors
= D-ala replaced with D-lactic acid
= removes vancomycin H bond = weaker interaction
What does translation require?
Ribosomal RNA
Messenger RNA
Transfer RNA
What does chloramphenicol do?
Bind to 50S portion + inhibit formation of peptide bond
What does tetracyclines do?
Interfere with attachment of tRNA to mRNA-ribosome complex
What does streptomycin do?
Change shape of 30S portion = code on mRNA read incorrectly
Which inhibit protein synthesis (translation)?
Aminoglycosides = gentamicin
Tetracyclines = doxycycline
Macrolides = clarithromycin
Chloramphenicol
Lincosamides
How do aminoglycosides inhibit protein synthesis?
Bind to 16S ribosomal DNA portion of 30S = read ribosome impaired
Conformational change in A site
Mistranslation of RNA template
= incorrect amino acid
What happens in aminoglycoside resistance?
Due to bacterial elaboration of resistance transfer factor mediated enzymes
= prevents ribosomal binding
What can aminoglycosides interact with?
Beta lactams
= gentamicin + beta lactam = acylation
Are tetracyclines bactericidal or bacteriostatic?
Bacteriostatic
How do tetracyclines work?
Bind to 30S
= aminoacyl-TRNA can’t bind
= stop further addition of amino acids
What is an example of tetracycline?
Doxycycline
What do tetracyclines involve?
Mg2+
What are the interactions with tetracycline for?
Antacids
Ca2+
Why do you avoid children having tetracyclines?
Form complex with Ca2+
= damage teeth + bones
Describe tetracycline epimerisation
Orientation of C-4 essential for bioactivity
Reprotonation top = regenerates tetracycline
Reprotonation bottom = inactive
At eqm mixture equal quantity of diastereomers
Describe tetracycline dehydration
Ideal geometry for acid catalysed dehydration
= biologically in active + deeper colour
What does tetracycline dehydration cause?
Nephrotoxicity
What are the adverse effects of tetracyclines?
Teeth staining
Kidney damage
Nausea
Vomiting
Diarrhoea
Are macrolides bacteriostatic or bactericidal?
Bacteriostatic
How do macrolides inhibit protein synthesis?
Bind to 23S rRNA polypeptide exit tunnel in 50S ribosomal subunit
= stops polypeptide from exiting
What are the drug interactions for macrolides?
Metabolised by CYP 3A4 into nitrosoalkanes
= benzodiazepines, statins, neuroleptics
Is chloramphenicol bacteriostatic or bactericidal?
Bacteriostatic
How does chloramphenicol inhibit protein synthesis?
Bind to large ribosome subunit 50S
= prevents binding of next charged tRNA
Why is chloramphenicol quite toxic?
Nitro group
What is chloramphenicol drug interactions?
Inhibits CYP 2C19 + 3A4
= tricyclic antidepressants, PPIs, macrolide antibiotics
Why should lincosamides not be given simultaneously with macrolides + chloramphenicol?
Similar mechanism on action to them
= cause antagonism + possible cross-resistance
Describe oxazolidinones
Bacteriostatic/cidal against gram +
How does oxazolidinones inhibit protein synthesis?
Binds to 50S subparticle
= before 30S + 50S complex is formed
= stops ribosome forming
What are antibiotics that inhibit nucleic acid transcription + replication?
Quinolones + fluroquinolones
Describe quinolones + fluroquinolones
Bactericidal
Gram +/-
How do quinolones + fluroquinolones inhibit nucleic acid transcription + replication?
Stabilising complex formed between DNA + topoisomerases
What are drug interactions for quinolones + fluroquinolones?
Complex metal ions = antacids
Theophylline
Digoxin
Which antibiotic caused injury to plasma membrane?
Polymixin B
Describe polymixin
Gram - active
How does polymixin cause injury to plasma membrane?
Bind to phosphate groups in bacterial membranes
Which antibiotics inhibit synthesis of metabolites?
Sulphonamides + trimethoprim
Are sulphonamides + trimethoprim bactericidal or bacteriostatic?
Bacteriostatic
How does sulphonamides + trimethoprim inhibit synthesis of metabolites?
Act as competitive inhibitors of dihydropteroate synthetase
Block biosynthesis of tetrahydrofolate
What are the adverse drug reactions of sulphonamides + trimethoprim?
Fever
Skin rashes
Allergic myocarditis
