Cell Wall Synthesis inhibitors Flashcards
Which are the cell wall synthesis inhibitors?
B-Lactams
Peptides
Fosfomycin
Bacitracin
Which agents fall under the B-Lactams?
Penicillins
Cephalosporins
Carbapenems
Monobactams
Which agents fall under the Peptides?
The Glycopeptides
Difference btwn gram +ive and -ive bacteria?
Gram +ive: contain a thick cell wall that consists of 40 layers of a peptidoglycan polymer. Retain Purple dye
Gram -ive: the peptidoglycan polymer is thin, is surrounded by a membrane and it also surrounds a periplasmic space. Retain Red dye
Process of Bavterial cell wall synthesis
Formation of sheets of amino sugars which are alternating reisdues of N-acetylglucosamine and N-acetyluramic acid( contains pentatpeptide side chains). Transpeptidase enzyme cross-links neighbouring amino sugar chains to form penta-glycine bridges between the side chains
Action of the B-Lactamsq
They inhibit the formation of the Peptidoglycin bridge by inhibiting the Transpeptidase enzyme
Are Penicillins Bacteriostatic or Bactericidal agents?
They are bactericidal agents–> kill bacteria
MOA of Penicillins
They inhibit the Transpeptidase enzyme during the Peptidoglycan synthesis by binding to the Cell wall (peptidoglycan) thus the enzyme cannot attach to it
–> cell wall gets defects= swelling of bacteria=lysis
In what state does the bacterial cell have to be in in order for the Penicillin to work?
It has to be actively growing/replicating/forming the cell wall
Bacterial Resistance against Penicillins
- Absence of cell wall: if there’s no cell wall then the penicillins cannot affect it.
- Metabolically inactive bacteria: if the bacteria is not actively growing (inherent resistance) they cannot affect it
- Altered Penicillin binding proteins: The Transpeptidase has altered its binding site
- Permeability barrier
- Some bacteria lack autolysins:
- Mutations can also reduce or eliminate activity
- B-Lactamase production–> cleaves the penicillin in surrounding media–> hydrolysis of B-Lactam ring–>inactivation
Action of B-Lactamases
cleave the B-Lactam bond to form an inactive acid
Penicilloic acid
What is a natural penicillin?
its produced by microorganisms that kill other microorganisms
Which are the natural penicillins
Penicillin G: Benzylpenicillin
Penicillin V: Phenoxymethylpenicillin
Characteristics of the Natural Penicillins
Both have a narrow spectrum i.e. target certain spectrum
Both are B-Lactamase sensitive therefore resistance develops easily
Spectrum/Clinical uses of Penicillin G
Gram +ive: Tonsillitis
Pneumonia
Gram -ive rod bacteria: Oropharyngeal infections (are sensitive to Penicillins)
Spiral-shaped bacteria: Syphillis
Gram +ive facultative anaerobes: Abscesses
Enterococci is less susceptible therefore used concurrently with Aminoglycosides
Which Bacteria have developed Resistance against Penicillin G
Gram -ive cocci: Meningitis
Gram -iive diplococci: Gonorrhoea
Grma =ive rod: tetanus, gangrene
Which is the 1st line treatment for Syphillis?
Penicillin G: IM injection
Against which bacteria is Penicillin G used as a Prophylaxis?
Streptococcal infections
Rheumatoid fever recurrence
Surgical/dental procedures on patients with valvular heart disorders
When is Penicillin G used as Initial Therapy?
for serious infections like infective Endocarditis, syphilis (depot prep benzathine penicillin G)
Difference between Penicllin G and V
Penicillin V is 2-4 times less active and potent than penicillin G
Spectrum/Clinical uses for Penicillin V
used mostly for treatment of less serioius infections like Streptococcal tonsillitis/pharyngitis
OR
used as follow-up antibiotic treatment after serious infections responded well to parenteral treatment
Which are the B-Lactamase resistant penicillins
Cloxacillin
Flucloxacillin
Spectrum/Uses of B-Lactamase resistant penicillins
used for treatment of mild B-lactamase positive Staphylococcal infections
Are less active than penicillin G–> much less potent
What are Broad spectrum Penicillins (aminopenicillins)
are broad spectrum penicillins with extended spectrum–> affect many gram +ive and -ive bacteria (gram -ive bacteria show widespread resistance)
Which are the B-Lactamase sensitive Aminopenicillins?
Amoxicillin (amoxycillin)
Ampicillin
VERY SENSITIVE THEREFORE RESISTANCE DEVELOPS EASILY
Which are the B-Lactamase resistant Aminopenicillins
Amoxicillin+Clavulanic acid (co-amoxiclav)
Which are the Aminopenicillins that extend the spectrum
Ampicillin+Cloxacillin in combination
Ampicillin is sensitive to B-Lactamase theredore combining it with an agent that in insensitive to B-Lactamase–> can target both types of bacteria
What is Clavulanic acid
its a B-Lactamase inhibitor
MOA of Clavulanic acid
it binds covalently and irreversibly near or in the acitve site of B-Lactamases = inhibition
Most gram -ive organsims are ireeversibly inhibited by it
Spectrum/Clinical uses of Ampicillin
most gram +ive bacteria+ Influenza
*most gram -ive bacteria are resistant to it
Spectrum of Amoxicillin
gram +ive spectrum similar to Pen G= incr. activity against Enterococci and Listeria
Gram -ive spectrum: H.influenza, E.coli, Proteus mirabilis, Salmonella & Shigella
Amoxicillin is drug of choice in
Otis media
Sinusitis lower RTI
Clinical Uses of Amoxixllin
Soft tissue infections
Cholecystitis, GIT infections (incl. thyroid)
UTIs
Prophylaxis to prevent infective Endocarditis
What are Antipseudomonal penicillins
They are extended spectrum antibodies.
Which are the Extended Spectrum Antipseudomonal penicillins
Piperacillin+Tazobactam(B-Lactamase inhibitor
Antipseudomonal pencillins are effective against
Most effective against Pseudomonas Aeruginosa
MOA of Antipseudomonal penicillins
They act synergistically with Aminoglycosides for empiric treatment of serious Pseudomonas infections
Which is the 1st line treatment for P.aeruginosa
Aminoglycosides
Ways to prolong action of Penicillin G
- Higher dosages=plasma level above MIC
- Combined with Probenecid: Probenecid competes with the Penicillin for the excretory route–> delayed excretion of penicillin= incr. T1/2
- Depot Formulations via IM injection: slow release of pencillin over time–> prolonged time spent in blood
- Inflammations: incr. penetration into CSF and synovial fluid
What are the Limitations to Penicillin G?
- Narrow spectrum: affects gram +ive
- Acid Labile
- B-Lactamase sensitive
S/Es of Pencillin G
-Antibodies formed: Penicillin G forms metabolites and if a patient develops a Hypersensitivity rxn antibodies form against those metabolites.
-Cross hypersensitivity between all penicillins: if you are allergic to one avoid the rest.
-Since its given at {very high} via IV or intrathecal injections, may cause Neurotoxic convulsions (eg. convulsions)
S/Es of B-Lactamase Resistant antibiotics/penicillins
-Cloxacillin is generally well-tolerated
–> mild GIT disturbance and hypersensitivity rxns
- Neutropenia and agranulocytosis
-Flucloxacillin–> precipitates Cholestatic hepatitis
S/Es of Extended Broad spectrum B-Lactam antibiotics/penicillins
-Superinfections esp. by Candida+ C.Difficule (antibiotic ass. colitis esp. Ampicillin)
-Rashes (toxin) rather than allergic rxn
-Reduce efficacy of COC pill
-GIT effects
-Infectious mononucleosis (amoxicillin)
S/E of Ampicillin
Weak oral absorption of ampicillin–> more destruction of microflora of GIT (causes diarrhea)
S/Es of Co-amoxiclav
High doses: GIT discomfort, diarrhea, N+V
Hepatitis and Chloestatic Jaundice–> Clavulanic acid
Amoxicillin and Clavulanic acid must be used with caution during Lactation–> excreted in mothers milk
SEs of Piperacillin
Same as Penicillin G
May cause potentiala bleeding diathesis
General SE in all Pencillins
Formulations as Na or K salts in high doses –> use in care in patients with cardiac and renal disease (may cause fluid retention, Hypocalcemia, hypernatremia, may precipitate arrythmias)
