Antimicrobial drugs Flashcards
bactericidal
killing bacteria
bacteriostatic
inhibiting/arresting the growth of bacteria
anti bitotic characteristics based on target/mode of action
Antibiotics interfere with/inhibit essential cellular structures/processes
Antibiotics target bacteria-specific structures/processes
Such modes of action make them
Toxic to bacteria only
Innocuous to humans (little or no-side effects)
The cell wall is a target for many antibiotics
The CW is responsible for cell integrity
The CW protects bacteria from toxic substances
Absence of functional CW = death (by autolysis)
Human cells do not have cell walls
The cell wall is an essential bacteria-specific organelle
Gram positive cell walls
The CWs of Gram +ve bacteria have thick layers of peptidoglycan chains
Each peptidoglycan chain is build up of covalently linked sugars
In addition short peptide chains are attached to NAM = N-acetylmuramic acid
Peptidoglycan chains cross-link via peptidyl bridges
Gram Negative cell walls
In contrast, the CW of Gram -ve bacteria have a thin peptidoglycan layer
This helps explain why antibiotics targeting peptidoglycan biosynthesis are not as effective against Gram -ve bacteria
Anitbiotics that target peptidoglycan biosynthesis
beta lactams — Penicillins, Cephalosporins, Carbapenems
Vancomycin
Beta-lactam antibiotics
are effective against growing and dividing cells
kill bacteria by autolysis (bactericidal)
resistant bacterial species produce beta-lactamase, a secreted enzyme which inactivates antibiotics by breaking down their beta-lactam ring
How do Beta-lactam antibiotics work?
Inhibit the enzymes involved in the transpeptidase cross-linking reaction
Interfere with linking the individual chains together
Disrupt PG synthesis leading to autolysis
Penicillins
Very effective against Gram +ve Some allergy reactions Aminopenicilins better tolerated Natural (Penicillin G) Aminopenicillin (amoxicillin, ampicillin
Cephalosporins
Different primary coverage: 1st – Gram +ve 2nd – Anaerobes 3rd – Gram –ve 4th - Pseudomonas
1st (Cefalexin; cefazolin)
2nd (Cefaclor, cefuroxime)
3rd (Cefixime, cefpodoxime)
4th (Cefepime)
Carbapenems
Broad spectrum Generally effective against all BUT: MRSA and VRE Only available IV Meropenem Ertapenem Imipenem
Vancomycin
An inhibitor of CW biosynthesis different mode of action to beta-lactams different chemical structure Glycopeptide antibiotic (more allergic reactions) Effective against MRSA Administered intravenously However emerging cases of resistance (VRSA; VRE)
Antibiotics inhibiting protein synthesis
Protein synthesis requires rRNA-Protein complexes known as ribosomes
There is no synthesis of proteins in the absence of
functional ribosomes
Bacterial ribosomes differ from those in humans
Examples of antibiotics which inhibit protein synthesis
Some bind to, and inhibit protein components of the 30S subunit
Tetracycline
Aminoglycosides (Gentamycin, Streptomycin)
Others bind to, and inhibit protein components of the 50S subunit
Macrolides (Erythromycin)
Chloramphenicol
Antibiotics inhibiting DNA biosynthesis
Fluoroquinolones
Fluoroquinolones
Broad-spectrum, synthetic
Inhibit bacterial enzymes (DNA gyrase) with essential roles in DNA replication
Effective against Gram –ve bacteria and intracellular pathogens (Legionella, Mycoplasma)
Higher levels of toxicity associated with them
Antibiotics inhibiting RNA biosynthesis
RNA biosynthesis requires specialised enzymes known as DNA-dependent RNA polymerases
Rifampicin
Rifampicin
Inhibits bacterial but not human RNA polymerases
Used predominantly for treating tuberculosis
Nucleic Acids biosynthesis could be targeted indirectly
Biosynthesis of nucleotides requires folic acid
Folic acid synthesis is a target of man-made antibiotics- antimetabolites
Sulfonamides – analogues of PABA, act by substrate competition
Trimethoprim inhibits dihydrofolate reductase
Co-trimoxazole – a mixture of both (5:1), inhibits both enzymes
Choice of antibiotic treatment depends on:
bacterial species susceptibility to drug site of infection safety of drug cost of therapy patient factors
Resistance to antibiotics comes from
Mutations in bacterial chromosomal genes encoding targets of common antibiotics (VGT)
Transfer between organisms of resistance genes carried by plasmids (HGT)
Biofilm formation
Biochemically resistance
Biochemically resistance is manifested by
(i) decreased accumulation of the drug – increased efflux or reduced permeability of the drug
(ii) enzymatic inactivation of the drug - secretion of Beta- lactamase
(destroys beta-lactam) or chloramphenicol acetyl transferase (inactivates chloramphenicol)
