Antibiotics Flashcards
Antibiotic classes
Cell wall inhibitors (penicillins, cephalosporins, glycopeptides)
Inhibitors of nuclear acid synthese (metronidazole)
Inhibitors of protein synthesis (aminoglycosides, macrolides, lincosamides, chloramphenicol, tetracyclines)
Inhibitors of metabolic pathways (folate synthesis inhibitors) (sulphonamides and trimethoprim)
MOA penicillin G (benzylpenicillin) & V
B-lactams bind to PBPs (enzyme responsible for final stages of peptidoglycan synthesis. Peptidoglycans confer wall strength and rigidity, essential for cell wall formation), causing accumulation of cell wall precursors. This initiates production of autolytic enzymes & cell lysis.
Spectrum of Penicillin G and V
Gram positives + Neisseria
Mechanism of resistance to penicillins
B lactamase produced by staph aureus. Attaches to B lactam so it can no longer bind PBPs.
Spectrum of Amoxicillin/Ampicillin
Essentially penicillin with altered side chains.
Gram positives + Neisseria, Haemophilus and E. Coli
(Side chain which allows it to get through porins of gram negatives)
Adverse effects of penicillins
Hypersensitivity reactions common. Less common: anaphylaxis, nephritis.
These occur because penicillins can react with our own proteins and become antigenic.
Drugs that overcome B-lactamase activity
Penicillin resistant SA: Dicloxacillin and Flucloxacillin
B lactamase inhibitors: clavulanic acid (administered as augmentin: clavulanic acid + amoxicillin)
MOA Cephalosporins
B lactam antibiotics with similar structure to penicillins, with similar mode of action but cover broader range of bacterial infections
Name a cephalosporin
Ceftriaxone
ARx cephalosporins
Similar to penicillins: hypersensitivity (about 10% of those allergic to penicillin are also allergic to this), rash, overgrowth of other organisms, diarrhoea common (may be due to c. difficile)
Name a glycopeptide
Vancomycin
MOA of glycopeptides
Inhibit cell wall synthesis of gram positives only (no action against gram -ve) by interfering with cell wall synthesis, binding to D-alanine-D-alanine ends of the peptide chain
Indication for glycopeptides
Reserved for serious infections where other treatments have failed (e.g. MRSA, MRS epidermatidis, those who are sensitive to penicillin and clostridium and c. difficile, which causes pseudomembranous colitis).
Treatment for helicobacter pylori
2 antibiotics: usually metronizadole and a penicillin plus proton pump inhibitor
Name a nucleic acid synthesis inhibitor
Metronidazole
What class does metronidazole belong to
Nucleic acid synthesis inhibitors
Uses of metronidazole
Aerobic bacteria (e.g. clostridium), aerobic protozoa (e.g. giardia), helicobacter pylori (used with penicillin and proton pump inhibitor)
Mechanism of action of metronidazole
Nitro group of metronidazole is reduced as it accepts electrons; its reduced intermediate products damage DNA and inhibit replication.
Mechanism of action of aminoglycosides
Enters bacteria via active transport and binds to 30S ribosome subunit, freezing it so no more protein can be produced.
Name an aminoglycoside
Gentamicin
ARx of gentamicin
Ototoxicity and nephrotoxicity (narrow therapeutic range(
Mechanisms of resistance to aminoglycosides
Target site alteration, alteration of cell wall permeability, aminoglycoside-modifying enzymes, which the bacteria may produce
Name three macrolides
Erythromycin (most commonly used for the treatment of stap and strep when hypersensitivity is a problem), clarithromycin (most commonly used against gram +ve bacteria), azithromycin (less active against gram positive organisms)
What class are erythromycin and azithromycin
Macrolides (inhibitors of protein synthesis)
Spectrum of activity
Wide - gram +ve cocci, chlamidya, anaerobes
Most commonly used for treatment of staph and strep when hypersensitivity is a problem
Erythromicin
Types of protein synthesis inhibitors
aminoglycosides, macrolides, lincosamides, chloramphenicol, tetracylines
Mechanism of action of macrolides
Inhibits protein synthesis by binding to the 50S subunit of the ribosome, inhibiting enzyme peptidyl-transferase, prevents transfer of the peptidyl tRNA from the A-site to the P-site, and thus inhibits protein synthesis
Resistance to macrolides
alteration of the target ribosome site and efflux of the drug from the cell
ARx Macrolides
nausea, upper GIT discomfort, and infrequently, deafness
and jaundice.
MOA lincosamides
Similar to macrolides in that they inhibit peptide bond formation.
Lincosamides spectrum of activity
gram positive aerobes and most anaerobes (broad spectrum).
Indication for lincosamides
Not used first up (it is 2nd line therapy in people who cannot handle conventional
therapy or where resistance is of concern). The more use an antibiotic has, the more
resistance bacterium become.
ARx for lincosamides
Antimicrobial associated diarrhoea
Tetracycline spectrum of activity
very broad spectrum of effects, on gram-positive, negative intracellular pathogens and mycoplasma (cell wall deficient bacteria). They tend to be bacteriostatic, not cidal.
MOA tetracyclines and examples
TETRACYCLINE & DOXYCYCLINE
They bind to the 30S subunit, distorts it such that anticodons of tRNAs cannot align properly with the codons of mRNA, inhibiting protein synthesis
Resistance to tetracylines
Resistance occurs because tetracyclins are widely used, and now many bacterial strains can produce efflux pumps to pump the antibiotic out.
ARx of tetracyclines
GIT intolerance (pain and diarrhoea), candidiasis due to overgrowth of normal flora, and interferes with bone development and browning of teeth.
CI for tetracylines
Contraindicated in those <8 years old and in pregnancy.
Name two inhibitors of metabolic pathways/folate synthesis inhibitors
sulphonamides (previously used for UTIs. No longer used due to toxicity) and trimethoprim
MOA trimethoprim
broad spectrum bacteriacidal agent which inhibits dihydrofolate reductase and thus inhibits folate synthesis in bacteria (folate is necessary for DNA and RNA synthesis)
Major use of trimethoprim
UTI’s with limited toxicity (but cannot use it during pregnancy)
Minimal Inhibitory Concentration (MIC)
the lowest concentration of an antibiotic which will inhibit the growth of a microorganism.
Minimal Bacteriocidal Concentration (MBC)
the lowest concentration of an antibiotic which will kill a microorganism.
Clinical uses of trimethoprim
Used on its on in UTI and respiratory tract infections, and with sulfonamides for p. jirovecii, which causes pneumonia in patients with AIDS
Clinical uses of penicillin
Depending on sensitivity testing:
- BENZYLPENICILLIN: Bacterial meningitis (caused by Neisseria meningitidis, streptococcus pneumoniae)
- FLUCLOX: bone and joint infections (e.g. with staph aureus)
- OTITIS MEDIA (organisms commonly include strep pyogenes and h. influezae): AMOXI
