antibiotics Flashcards
what are antibiotics
Chemical compounds used to treat infections caused primarily by bacteria; they should be sufficiently non-toxic to be given to the infected host’
what are natural antibiotics
(‘true antibiotics’); produced naturally(Penicillium chrysogenum produces penicillin)
what are semi-synthetic antibiotics
chemically modified natural antibiotics (e.g. ampicillin)
what are the different ways antibiotics can work
disrupting cell wall synthesis
interfering with nucleic acids
protein synthesis
metabolism
The β-Lactam Antibiotics are also known as …
The Penicillins are a form of cell wall disruptants
how do the β-Lactam antibiotics work
-lactam antibiotics inhibit the transpeptidase (similar structure to D-alanyl D-alanine in the peptide chain)
competitive inhibition; irreversible binding
what are the clinical uses of β-Lactam
URTI (eg. tonsillitis)
LRTI (eg. pneumonia)
STI (eg. gonorrhoea, syphilis)
Skin and tissue infections
NB. Hypersensitivity and anaphylactic shock in some patients; alternative antibiotics warranted
what are the Quinolones
Synthetic antibacterial compounds (made in lab) that act as DNA gyrase inhibitors
Derivatives of nalidixic acid (fluorinated) and an example of dna disrup
describe the Mechanism of Action of quinolones
Quinolone antibiotics interfere with changes in DNA supercoiling by binding to DNA gyrase (topoisomerase II [1st and 2nd generation Qs] or topoisomerase IV [3rd and 4th generation Qs])
Prevent DNA unzipping
This leads to the formation of double-stranded DNA breaks and cell death
what are the clinical uses of Quinolones
UTIs
MDR Infections
Pyelonephritis
Prostatitis
Pneumonia
Highly restricted use in children in UK (anthrax or cystic fibrosis pulmonary infection) – musculoskeletal side effects
what are Macrolides
is a natural product made of polyketides erythromycin from Streptomyces erythraeus
what are the Macrolides effective against
Mostly G+ (limited G-) considered broad spectrum
Most active against G+ cocci (mainly staphylococci and streptococci)
Macrolides are also active against Mycobacteria, Mycoplasma, Ureaplasma, spirochetes, and other organisms.
what is the Mechanism of action of macrolides
Protein synthesis inhibitors
Reversible binding to the P site on 50S ribosomal subunit
Bacteriostatic
Disruption of proteome leading to cell death
The Macrolides: clinical usage
-Gram-positive infections
Streptococci
Pneumococci
Staphylococci
Enterococci
Chlamydia
Mycobacteria
-Gram-negative infections
Bordetella pertussis
Haemophilus influenzae
what are The Aminoglycosides
Natural products - amino sugars bonded by glycosidic bonds
Streptomycin from Streptomyces griseus
Bactericidal (aerobic G-)
Mostly G- bacteria [not anaerobes] (+ Mycobacteria)
Aminoglycosides: Mechanism of action
Protein synthesis inhibitors
Bind to the aminoacyl site of 16S rRNA in 30S subunit of the ribosome (irreversible)
Cause mis-incorporation of amino acids into elongating peptides
Incorporation of misfolded membrane proteins into the cell envelope leads to increased drug uptake
Increase in ribosome binding
Cell death
what are the clinical uses of aminoglycosides
Use for antibiotic resistant G- infections
Incorporated into combination for G+
Issues with nephrotoxicity and ototoxicity
Mycobacterium tuberculosis, NTM and Neisseria gonorrhoeae
what are The Tetracyclines
Natural products – (Aureomycin (CTC) from Streptomyces aureofaciens
Broad spectrum (better against G+)
Tetra- (4) -cycl- (hydrocarbon ring) -ine (derivative)
Derivatives of polycyclic naphthacene carboxamide
Bacteriostatic
Mechanism of action of Tetracyclines:
Protein synthesis inhibitors
Inhibit binding of aminoacyl-tRNA to mRNA-ribosome complex in the A site of 30S robosomal subunit
Stall protein synthesis
Reversible binding
Cause disruption to proteome leading to bactiostasis
Also bind matrix metalloproteinases (useful!)
descrive Tetracyclines: clinical uses
UTI
U/LRTI
GI Tract infections
Chlamydia (if allergic to β-lac or macrolides)
Acne
Rickettsia
Brucellosis
Spirochetal infections (syphilis and Lyme disease (borreliosis))
Anthrax, plague, Legionnaires’ disease
Cholera
how are tetracyclines useful as chemicals
