Download 3. Inhibition f nucleic acid synthesis

3. Inhibition f nucleic acid synthesis
Sulfonamides & Trimethoprim
Inhibit the synthesis of folic acid the main donor
of the methyl groups that are needed for synthesis of
adenine,
guanine and thymine.
A combination of both is often used because bacteria
resistant to one drug will often be inhibited by the other.
Quinolones
Inhibit DNA synthesis by blocking the DNA
gyrasethe enzyme that unwinds DNA strands so
that they can
replicate.
They are a family of drugs.
Rifampin
Inhibits RNA synthesis in bacteria by blocking RNA
polymerase, which synthesizes RNA.
4. Altering cell membrane function
Anti-fungal drugs are the most important in this
category, because fungal cell membranes contain
ergosterol, while human cell
membranes have cholesterol. Bacteria, with exception of
Mycoplasma, don’t have sterols in their membranes and
thus are
resistant to these drugs.
Amphotericin B
Disrupts fungal cell membrane by binding to the site of
ergosterol in the membrane.
It is used to treat systemic fungal infection, but it has
side effects, especially on kidneyAzoles
Are antifungal drugs that inhibit ergosterol synthesis.
The azole family is useful in systemic as well as skin
and mucous membrane infections.
5. Additional drug mechanisms
Isoniazid
Inhibits the synthesis of mycolic acid, a long chain
fatty acid found in cell of mycobacterium.
It is a prodrug that requires a bacterial peroxidase
(catalase) to activate the isoniazid to become the
metabolite that
inhibits mycolic acid synthesis.
Isoniazid is the most important drug in treatment of
tuberculosis + other mycobacterial diseases.
Mitronidazole
Is effective against bacteria and certain protozoa
because it acts on electron sink it takes away the
electrons the
organism needs to survive.
It also forms toxic intermediates which damage
DNAzoles
Are antifungal drugs that inhibit ergosterol synthesis.
The azole family is useful in systemic as well as skin
and mucous membrane infections.
5. Additional drug mechanisms
Isoniazid
Inhibits the synthesis of mycolic acid, a long chain
fatty acid found in cell of mycobacterium.
It is a prodrug that requires a bacterial peroxidase
(catalase) to activate the isoniazid to become the
metabolite that
inhibits mycolic acid synthesis.
Isoniazid is the most important drug in treatment of
tuberculosis + other mycobacterial diseases.
Mitronidazole
Is effective against bacteria and certain protozoa
because it acts on electron sink it takes away the
electrons the
organism needs to survive.
It also forms toxic intermediates which damage DNA.
Chemoprophylaxis
These antimicrobial drugs are also used to prevent
infectious diseasesA1They are given mainly in 3
circumstances:
- To prevent surgical wounds from getting infected
- To prevent opportunistic infections in
immunocomprised patients
- To prevent infections in those known to have been
exposed to pathogens that can cause serious infectious
diseases3. Bacterial resistance to antibacterial drugs:
significance and mechanisms of action.
The 4 mechanisms of antibiotic resistance are:
2) Enzymatic degradation of the drug
3) Modification of the drugs’ target
4) Reduced permeability of the drug
5) Active export of the drug
Most drug resistance is the result of a genetic chance in
the organism, caused either by a chromosomal mutation
or
acquisition of a plasmid or transposon.
Genetic basis of resistance
1. Chromosomal mutation
Either changes the target of the drug so the drug won’t
be able to bind, or it changes the membrane so that the
drug doesn’t penetrate well into the cell.
This occurs at low frequency, affecting only one drug
or one family of drugs.
2. Plasmids
Cause drug resistance by encoding enzymes that
degrade or modify the drug
This happens at higher frequency, affecting multiple
drugs.
3. Transposons
Are small pieces of DNA that move from one site on
the bacterial chromosome to another or from one
bacterial chromosome to plasmid DNA.
They often carry drug resistant genes.
Non genetic basis of resistance
Non genetic reason why bacteria may not be inhibited
by antibiotics are that drugs may not be able to reach the
bacteria located in the middle of an abscess and also that
certain drugs, like penicillin don’t affect bacteria that are
growing. The presence of foreign bodies also makes it
more difficult to achieve a successful antibiotic
treatment.
Specific mechanism of resistance
Resistance to penicillin and cephalosporins is mediated
by 3 mechanisms:
2) Degradation by ß-lactamase (THE MOST
IMPORTANT MECH.!)
3) Mutation in genes for penicillin binding proteins
4) Reducing permeability
Antibiotic sensitivity testing
The minimal inhibitory concentration (MIC) is the
lowest concentration of drug that inhibits the growth of
the
bacteria isolated from the patient. In this test though, it
isn’t known if the inhibited bacteria have been killed or
just
stopped growing.
The minimal bactericidal concentration (MBC) is
the lowest concentration of drug that kills the bacteria
isolated
from the patient. In certain diseases, like endocarditis, it
is important to use a concentration of drug that is
bactericidal.
Use of antibiotic combination
Two or more antibiotics are used under certain
circumstances, like in life threatening infections before
the cause
has been identified, to prevent the emergency of resistant
bacteria during prolonged treatment regimes, and to
achieve a synergic effect.
Synergism: when the effect of two drugs together is
significantly higher than the sum of the effect of the
two drugs
alone.
Antagonism: when the effect of the two drugs
together is significantly lower than the effect of the
effective drug
Alone
.