RO L6 Flashcards
Antimicrobial agent/drug:
Chemical substance used to treat diseases caused
by pathogenic microbes
Antibiotic:
Chemical substance (/drug) produced by microorganisms, with the
capacity to control growth/kill microbes
Penicillin
Penicillium notatum inhibited
S.aureus
Properties of Useful Chemotherapeutic Agents
- Selectively toxic to pathogens; non-toxic to host and minimal effect
on normal microbial flora – determine chemotherapeutic index - Should not stimulate an allergic reaction (hypersensitivity)
- Host should not destroy or neutralise drug before effective
- Pathogens should not easily become resistant to the drug
- Agent should reach the site of infection (solubility)
Spectrum of activity
Range of different microorganisms treatable
with an agent
- Broad spectrum
Active across a wide range of taxonomic
groups; useful for untargeted treatment without pathogen
identification
Narrow spectrum:
Specifically targets small number of
organisms; may protect host microflora; reduces development
of drug resistance
Five major modes of action of common
antimicrobial agents
- Inhibition of cell wall synthesis
- Disruption of cell membrane function
- Inhibition of protein synthesis
- Inhibition of nucleic acid synthesis
- Action as antimetabolites
1 – Inhibition of Cell Wall Synthesis
Peptidoglycan in Bacterial Cell Wall; not found in mammalian cells
Disruption of Cell Wall integrity cell lysis (osmotic pressure)
* Enzyme interference
* Actively dividing cells
Penicillin inhibits linking of
peptidoglycan rows by binding
to transpeptidase (PBP)
Interfere
with PG
crosslinking:
Targets
PBP
Penicillins: Bactericidal; All contain a β-lactam ring;
Natural penicillins (G, V) are penicillinase sensitive and
narrow spectrum. Semi-synthetic penicillins are modified
to increase penicillinase resistance and broaden spectrum
(e.g.methicillin, ampicillin, amoxicillin)
* Cephalosporins: Effective against more Gram-negatives;
Resistant to Penicillinases; More expensive; Mainly IV/IM
Interfere
with linear
PG strand
formation
Bacitracin: Polypeptide antibiotic; Effective against Gram
positives; Topical application
* Vancomycin: Glycopeptide antibiotics; narrow spectrum;
toxic; Penicillinase-resistant
2 – Disruption of Cell Membrane Function
Alter permeability of bacterial cell membranes; Polypeptide
antibiotics; clinical application limited to certain members due to
similarities between host and bacterial cell membranes
* Polymyxins: (A, B, C, D, E) used only when pathogen is
resistant to other less toxic antibiotics; Gram negatives; Topical
* Nystatin: combine with sterols; therefore effective against
mycoplasmas (and also systemic fungal infections).
* Colicins: Bacteriocin of E.coli; encoded by Col plasmid, which
also codes for immunity protein. Kills bacterial cells not
carrying the plasmid e.g. cells of same species
3 – Inhibition of Protein Synthesis
Takes advantage of differences between bacterial and eukaryotic
ribosomes – selective toxicity
Aminoglycosides: Amino sugars linked by glycoside bonds. Broad
spectrum. Bacteriocidal; bacteriostatic at lower doses. Work
synergistically with other compounds (e.g. penicillin)
Streptomycin (1940s); now has high resistance levels; toxic. Other
compounds (kanamycin, gentamicin etc.)
* Tetracyclines: Interfere with tRNA attachment. Bacteriostatic; very
broad spectrum; can inhibit intestinal microflora
* Chloramphenicol: Bacteriostatic; Broad Spectrum; Inhibits
peptide bond formation. Damages bone marrow
* Macrolides: Erythromycin – Bacteriostatic. Can not penetrate
Gram negative cell walls. Used as an alternative to Penicillin
4 – Inhibition of Nucleic Acid Synthesis
Can be Toxic to host cells due to common targets
Rifampin: Inhibits mRNA synthesis by binding RNA polymerase;
High absorbance into tissues and cells; Bactericidal; Broad
Spectrum; Interacts with other drugs; Treatment of mycobacteria
infections-leprosy and tuberculosis
* Quinolones: Blocks bacterial enzyme that unwinds DNA prior to
replication; Broad spectrum; Used for UTIs; Can affect cartilage
development
5 – Action as Antimetabolites
Compounds that interfere with metabolic reactions by:
1) Competitive inhibition of enzymes or
2) Erroneous incorporation into important molecules
Antimetabolites are structurally similar to normal
metabolites – molecular mimicry
Competitive Inhibition:
Bacterial cells require PABA to make folic acid (for synthesis of
nitrogenous bases in DNA). This process is inhibited by
sulphonamides or PAS.
Animal cells lack enzyme that makes folic acid so does not
affect animal cell metabolism
Sulfonamides: Bacteriostatic; Oral administration
Erroneous incorporation:
Vidarabine and Idouridine are incorporated into DNA and can block
replication and transcription due to disruption of base-pairing.
Host toxicity = Bacterial toxicity (Mainly used to treat viral infections)
