Antibiotics Flashcards
The 5 main target sites for antibacterial agents:
- cell wall synthesis
- cytoplasmic membrane function
- protein synthesis
- nucleic acid synthesis
- metabolic pathway
Which antibacterial agent has the best selective toxicity?
Antibacterial agent targeting cell wall synthesis because human cells do not have cell wall
Famileis of drugs that inhibit Send wall synthesis
- Beta lactams including monobactams, carbapenem, penicillin and cephalosporins.
- Glycopeptides including vancomycin
- bacitracin
- subactams
Antibiotics inhibiting cell wall synthesis are bactericidal or bacteriostatic?
Bactericidal
What is the target beta lactams?
Penicillin binding proteins
What is beta-lactamase?
An enzyme produced by bacteria that provides multi resistance to beta-lactam antibiotics
Bacteria that beta-lactam can’t act on:
Bacteria that do not have a cell wall like mycoplasma and intracellular bacteria
Inhibitors of beta lactamase:
Clavulanic acid and sulbactam
Mechanism of action of beta-lactams
They will bind to transpeptidase active site of penicillin binding proteins thus inhibiting the formation of cross linking and cell wall synthesis
All penicillin antibiotics are sensitive to the acidity of the stomach except those two:
Amoxicillin and penicillin V
Penicillins that are resistant to beta lactamase:
Nafcillin, oxacillin and methicilin
Penicillin V:
Active against gram-positive bacteria
Sensitive to Beta lactamase
Oxacillin methicillin and nafcillin:
Less active against gram-positive and inactive against gram negative
Resistant to beta lactamase
Ampicillin and piperacillin:
Active against gram positive and gram negative bacteria
Sensitive against beta lactamase
Amoxicillin
Less sensitive to beta lactamase
Taken orally
Better absorbed than ampicillin
Penicillin V
Acts like penicillin G but taken orally
MRSE
Methicillin resistant staphylococcus epidermidis
MRSA
Methicillin resistant staphylococcus aureus
How resistance is acquired by staphylococcus bacteria?
They have a MECA gene which will Produce new penicillin binding proteins that have a lesser affinity to penicillin and at the same time inactivating normal penicillin binding proteins.
ESBL
Extended spectrum beta lactamase
How beta lactamase inactivate penicillin?
By converting the 6-aminopenicilanic acid which is the compound that has the anti-bacterial activity, into 6-aminopenicilloic acid inactive against bacteria but have a property of an hapten
Hapten:
It is a molecule that has lost its capacity to produce disease but has preserved its antigenicity and can stimulate the immune system causing an allergic reaction
manifestations of an allergic reaction due to penicillin;
Skin rash and edema
Clavulanic acid
It’s a suicide inhibitor that has the capacity to inhibit the activity of beta lactamase.
It can’t be administered alone since it has o anti-microbial or antibacterial properties so it should be combined with another antibiotic and the junction with beta lactamase will make this antibiotic more effective.
First generation of cephalosporins
Activity similar to ampicillin
More active against gram-positive and less against gram-negative
Second generation of cephalosporins
Expended activity against Enterobacteriaceae which our gram-negative bacilli except Pseudomonas
Less active against gram-positive cocci
Active against haemophilus and anaerobes and can cross the blood brain barrier
Third generation of cephalosporins
More expanded activity against Enterobacteriaceae including Pseudomonas
Less active against gram-positive cocci and can cross the blood brain barrier
Fourth generation of cephalosporins
Active against pseudomonas
Active against streptococcus and methicillin susceptible staphylococcus
Superinfection
When we give an antibiotic which is more active against gram-negative bacteria for example in an E. coli infection, the normal flora will be imbalanced, this will activate certain bacteria like staphylococcus aureus causing a superinfection. In this case the antibiotic given is only treating the E. coli and complications will appear due to staph infection.
Broad-spectrum antibiotic
Antibiotic covering many types of bacteria like gram-negative, gram-positive, aerobics, anaerobic…
Most broad-spectrum antibiotic:
Carbapenems
They are active against gram-negative, gram-positive and anaerobes (Including Pseudomonas)
Monobactam
Limited to Gram-negative bacteria
Resistant against beta-lactamase
Origin of bacitracin
Bacteria called Bacillus Subtilis
Bacitracin
Active against positive bacteria
It is poorly absorbed by the G.I. tract and has many toxic side effects so it is not given systemically it’s only given externally as an ointment against gram-positive bacteria.
It prevents the phosphorylation of phospholipid carriers like Bactoprenol
It prevents regeneration of carriers necessary for synthesis to continue.
Vancomycin
It’s a glycopeptide that acts only against gram-positive bacteria since it cannot cross the outer membrane of negative bacteria due to its size
It prevents the separation of the fifth amino acid so it acts at the level of the element D Alanine-D-Alanine inhibiting formation of cross linking
Resistance to vancomycin
Some bacteria have D-alanine-D-lactate where vancomycin can’t act.
Other bacteria like enterococci have a chromosomal mediated resistance to vancomycin
Antibiotic Associated Diarrhea
When we are taking an antibiotic against a certain type of bacteria other bacteria that are part of our normal flora will increase the number and become pathogenic causing bacteria
Antibiotic used to treat antibiotic associated diarrhea
Vancomycin and metronidazole
Polymyxin B
Active only against gram negative bacteria
Binds to lipid A and phospholipids then cause disruption of cytoplasmic membrane causing the destruction of the whole bacteria cell
Antibiotics that bind 30 S subunit of ribosomes
Aminoglycosides and tetracyclines
Antibiotics that bind 50 S subunits of ribosomes
Lincosamides
Chloramphenicol
Macrolides
Clindamycin
Aminoglycosides
Acts on anaerobic Gram negative bacteria
To be effective they should be used in combination with another antibiotic
-icin Aminoglycosides:
Amikicin
Gentamicin
Netilmicin
-ycin Aminoglycosides
Tobramycin neomycin kanamycin streptomycin spectinomycin
Least toxic aminoglycosides antibiotic:
Netilmicin
Amikacin:
A semi synthetic the riveter of kanamycin
Active against gentamicin resistant gram-negative rods
Used preoperatively and post operatively to suppress microbial flora and avoid infections
Gentamicin
Broad-spectrum aminoglycoside used against aerobic gram-negative and gram-positive bacteria
Taken parenterally orally or as an ointment for the eye infections
Tobramycin
Activity similar to gentamicin but slightly better against Pseudomonas aeruginosa
Nowadays Pseudomonas has acquired resistance against tobramycin so it is no longer used to treat it except when it is a non-resistant strain
Kanamycin
No longer in clinical use
Only used as a prophylaxis to suppress microbial flora and avoid infections
Neomycin
Topical use when contaminated mucosal surfaces, too toxic to be used to systemically
About spectinomycin:
Used via a single dose IM injection to treat gonorrhea caused by Beta lactamase producing gonococci.
Alternative drug to penicillin
cause pain at the site of infection nausea and fever.
Streptomycin
The oldest aminoglycosides
What day is restricted for treatment of tuberculosis.
Has acquired chromosomal mediated resistance and then plasmid mediated resistance
No longer used alone but has to be combined with other drugs
Side effects of streptomycin
Tinnitus
Vertigo
Ataxia
Indications for aminoglycoside therapy
Only used for severe and life-threatening infections: Gram-negative septicemia Bacterial endocarditis Septicemia of unknown etiology Post surgical abdominal sepsis Pyelonephritis Staphylococcus aureus septicemia
Antibiotics acting on elongation phase of protein synthesis
Tetracyclines clothes on for Nicole chloramphenicol
Lyncosamids
macrolides
fusidic acid
Members of tetracycline
Chlortetracycline
Deoxycycline
Oxytetracycline
Tetracycline Minocycline
Tetracyclines are bacteriostatic or bactericidal
Bacteriostatic
Tetracycline shouldn’t be prescribed for
Pregnant women and children under 6 years old because tetracyclines will deposit on bone and cartilage leading to formation of yellow teeth
Chloramphenicol is bacteriostatic or bactericidal
Bacteriostatict
About chloramphenicol:
They bind 50s subunit of ribosome by blocking amino acid attachment
It was previously used in the treatment of salmonella typhi but it had severe toxic side effects so it’s no longer used.
How bacteria synthesize its own folic acid?
PABA in the presence of dehydropteroate synthase Relate formation of dehydropteroic acid then dehydrofolic acid which in the presence of dehydrofolate synthase will produce tetrahydrofolic acid.
Antimetabolites
Sulfonamides
Daspone
Trimethoprim
Bactrim composition
One part of trimethoprim and five parts of sulfonamides
About Bactrim
It is effective against mini gram-negative and gram-positive bacteria. It can be used for urinary tract infections but can cause an overgrowth of fungi causing genital tract itching for females due to overgrowth of Candida albicans
