Antimicrobials [17-18] Flashcards
What is selective toxicity
Using antibiotics to exploit difference in processes & structures of pro/eukaryotes to reduce host cell toxicity
E.g cell wall
2 types of antibiotic
Bacteriostatic (inhibit multiplication)
Bactericidal
What do antibiotics target in bacteria
Cell wall synthesis
Membrane synthesis
Protein synthesis
Metabolic pathways
Nucleic acid synthesis
Is cell wall thicker in gram positive or gram negative
Gram positive
Explain crosslinking
Transpeptidase links L-lys D-ala D-ala residues from different cell walls
Penicillin MOA
Binds to transpeptidase so it can inhibit cross linking
Example of 4 b-lactams
Penicillin
Cephalosporin
Monobactam
Carbapenem
What is flucloxacillin
Beta lactamase resistant penicillin
Acts of gram positive
Gram positive are more reliant on cross linking because they have a larger cell wall
What is a good all rounded penicillin
Amoxicillin - broad spectrum pencilling
For gram positive and negative
Describe cephalosporins
Beta lactam ring
Bind to penicillin binding protein
Prevents cross linking
Treats pneumonia and meningitis
Can cause diarrhoea
What is given in the case of a penicillin allergy
Monobactams
B lactam ring is peripheral
Beta lactamase resistant
Against gram neg
Mechanisms of penicillin resistance
Porin downregulation
Inactivation of antibiotic via enzymes
Production of efflux pumps to pump antibiotics out of cell
Target site modification
Production of beta lactamase
Modification of penicillin-binding proteins
Explain penicillin allergy
Antigens are degradation products of penicillin
Rash
Itching
Could cause anaphylactic shock
Lack of consciousness
4 antibiotics that inhibit protein synthesis
Streptomycin
Chloramphenicol
Erythromycin
Tetracyclines
Streptomycin MOA
Changes shape of 30s portion of ribosome
mRNA code read incorrectly
Chloramphenicol MOA
Binds 50s portion of ribosome
Inhibits peptide bond formation
Erythromycin MOA
Binds to 50s portion of ribosome
Prevents translocation of ribosome along mRNA
Tetracyclines MOA
Interfere with attachment of tRNA to mRNA-ribosome complex
Competitively binds A site
- Chlamydia
Resistance a growing problem
What drug class is is streptomycin
Aminoglycoside
Which antibiotics activity is enhanced by penicillins
Aminoglycosides
What drug class is erythromycin
Macrolide
Macrolides pharmacokinetics & adverse effects
Oral - enteric coated
Most effective against gram positive
Metabolised by CYP3A4
Resistance - efflux or methylation of ribosomal targets
Heart arrhythmias
GI disturbance
Chloramphenicol pharmacokinetics & adverse effects
Oral / IV
Resistance - enzymatic inactivation by acetyltransferase, efflux, ribosomal mutations
Grey baby syndrome
What is folate
Made from PABA - component in DNA synthesis
What inhibits conversion of PABA to folate
Sulfonamides
What inhibits folate utilisation
Trimethoprim
Sulphonamide PK
Crosses BBB
N-acetylated in liver
Trimethoprim most common use
UTI and respiratory tract infection
What do fluoroquinolones do
Inhibit DNA gyrase
Blocks DNA supercoiling
Fluroquinolones PK
Oral
Crosses BBB
gram +ve and -ve
Inhibits CYP1A2
Affects GI
Examples of mycobacteria and
Mycobacterium tuberculosis
Mycobacterium leprae
Mycobacteria traits
Thick waxy lipid-rich hydrophobic cell walls
Contain mycolic acids in cell wall
Can survive in macrophages
Becoming a major problem in immunocompromised patients
2 mycobacterium treatments
Rifampicin
Daptomycin
Rifampicin traits
Derivative of Rifamycin
Inhibits prokaryotic DNA dependent RNA polymerase
Good against +ve -ve and mycobacteria
Potent inducer of CYP3A4
4 forms of antibiotic resistance
Modified permeability - porin substitution
Drug inactivation - beta lactamases
Interaction prevention - modified penicillin binding proteins
Drug conc regulation - efflux
3 methods of acquiring resistance
Transformation
Transduction
Conjugation
What is transformation
Transfer of free DNA (containing antibiotic resistant gene) to competent recipient cell (can take up DNA)
What is transduction
Transfer of bacteria DNA containing antibiotic resistance gene via bacteriophage
What is conjugation
Plasmids transferred by conjugation
Direct contact between cells
Doesn’t require bacteria to be the same species
How can we tackle antibiotic resistance
Improve public awareness
Reduced inappropriate antibiotic use
Invest in drug R&D
Reduce use of broad spectrum antibiotics in livestock
