antibiotics

Question 1

what are antibiotics

Answer 1

Chemical compounds used to treat infections caused primarily by bacteria; they should be sufficiently non-toxic to be given to the infected host’

Question 2

what are natural antibiotics

Answer 2

(‘true antibiotics’); produced naturally(Penicillium chrysogenum produces penicillin)

Question 3

what are semi-synthetic antibiotics

Answer 3

chemically modified natural antibiotics (e.g. ampicillin)

Question 4

what are the different ways antibiotics can work

Answer 4

disrupting cell wall synthesis
interfering with nucleic acids
protein synthesis
metabolism

Question 5

The β-Lactam Antibiotics are also known as …

Answer 5

The Penicillins are a form of cell wall disruptants

Question 6

how do the β-Lactam antibiotics work

Answer 6

-lactam antibiotics inhibit the transpeptidase (similar structure to D-alanyl D-alanine in the peptide chain)
competitive inhibition; irreversible binding

Question 7

what are the clinical uses of β-Lactam

Answer 7

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

Question 8

what are the Quinolones

Answer 8

Synthetic antibacterial compounds (made in lab) that act as DNA gyrase inhibitors
Derivatives of nalidixic acid (fluorinated) and an example of dna disrup

Question 9

describe the Mechanism of Action of quinolones

Answer 9

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

Question 10

what are the clinical uses of Quinolones

Answer 10

UTIs
MDR Infections
Pyelonephritis
Prostatitis
Pneumonia
Highly restricted use in children in UK (anthrax or cystic fibrosis pulmonary infection) – musculoskeletal side effects

Question 11

what are Macrolides

Answer 11

is a natural product made of polyketides erythromycin from Streptomyces erythraeus

Question 12

what are the Macrolides effective against

Answer 12

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.

Question 13

what is the Mechanism of action of macrolides

Answer 13

Protein synthesis inhibitors
Reversible binding to the P site on 50S ribosomal subunit
Bacteriostatic
Disruption of proteome leading to cell death

Question 14

The Macrolides: clinical usage

Answer 14

-Gram-positive infections
Streptococci
Pneumococci
Staphylococci
Enterococci
Chlamydia
Mycobacteria
-Gram-negative infections
Bordetella pertussis
Haemophilus influenzae

Question 15

what are The Aminoglycosides

Answer 15

Natural products - amino sugars bonded by glycosidic bonds

Streptomycin from Streptomyces griseus
Bactericidal (aerobic G-)
Mostly G- bacteria [not anaerobes] (+ Mycobacteria)

Question 16

Aminoglycosides: Mechanism of action

Answer 16

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

Question 17

what are the clinical uses of aminoglycosides

Answer 17

Use for antibiotic resistant G- infections
Incorporated into combination for G+
Issues with nephrotoxicity and ototoxicity
Mycobacterium tuberculosis, NTM and Neisseria gonorrhoeae

Question 18

what are The Tetracyclines

Answer 18

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

Question 19

Mechanism of action of Tetracyclines:

Answer 19

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!)

Question 20

descrive Tetracyclines: clinical uses

Answer 20

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

Question 21

how are tetracyclines useful as chemicals

Answer 21