Antibacterials I Flashcards
What are the examples of inhibitors of cell wall synthesis ?
β-lactams, cycloserine, vancomycin and bacitracin
What are the categories of β-lactam antibacterials?
Penicillins
Cephalosporins
Monobactams
Carbapenems
What are the two enzymatic activities of Penicillin Binding Proteins?
Transpeptidase: cross-links amino acid side chains
Glucosyltransferase: links subunits of glycopeptide polymer
What is the general structure of penicillins?
Penicillin nucleus
6-amino acid penicillanic acid
β-lactam nucleus
What is the general structure Cephalosporins?
Cephalosporin Nucleus
7 - amino acid cephalosporanic acid
β-lactam nucleus
Are β-lactams mainly bactericidal or bacteriostatic?
Mainly bactericidal
What is the mechanism of action of β-lactams?
Bind to specific PBP located inside bacterial cell wall
Inhibit transpeptidase
Inhibit peptidoglycan cross-link formation during cell wall synthesis
Bacterial cell wall enzymes (autolysis) cause lysis
What is the spectrum activity of Penicillins?
Gram +/-
Anaerobes
What is the spectrum activity of Carbapenems?
Broad Gram -
Anaerobes
Narrow Gram +
What is the spectrum of activity of Monobactams?
Aerobic
Gram -
What is the spectrum activity of Cephalosporins?
1st and 2nd generations: Mostly gram + and some gram -
3rd and 4th generations: Most gram -
What is the mechanism of bacterial resistance to penicillins and cephalosporins?
Inactivation of drug by β-lactamase
Altered structure of PBP
Efflux pump
Presence of permeability barrier: mainly occurs in gram - bacteria that have an outer membrane that limits penetration of hydrophilic antibiotic
What are β-lactamases?
A family of enzymes that limit the efficacy of β-lactams
Can the β-lactamase activity be transferred?
Yes, it is genetically controlled and can be transferred from one bacterium to the next (through the transfer of plasmids)
What are the classes of penicillins?
Natural Penicillin
β-lactamase resistant penicillins
Extended spectrum (β-lactamase sensitive)
What are the examples of natural penicillins?
Benzyl-penicillin & analogs
What are examples of extended spectrum penicillins?
Aminopencillins
Antipseudomonal Penicillins
What makes up the penicillin nucleus?
Thiazolidine ring and lactam ring
What is the chief structural requirement of the penicillin for?
Biological activity
What happens if there is metabolic transformation or chemical alteration to the penicillin nucleus?
Loss of all significant antibacterial activity
What are natural penicillins made from?
A fungus Penicillium Chrysogenum
Are natural penicillins resistant or sensitive to β-lactamases?
Sensitive to destruction
What are the pharmacokinetics of natural penicillins?
Penicillin G: IV or IM
Benzathine Penicillin G: IM (sustained release)!
What is the spectrum of activity pf natural penicillin, Penicillin G?
Gram +/- cocci
Gram + bacilli (non β-lactamase producing)
What are the examples of non-β-lactamse producing Gram + bacilli?
Staphylococcus
Streptococcus
Pneumococcus
Clostridium
Neisseria meningitis
Treponema
What is the pharmacokinetics of natural Penicillin, Penicillin V?
Given orally
What is the spectrum of activity of Penicillin V?
Same as Penicillin G but less potent
Used in gonorrhoea and meningococcal meningitis
What are examples of β-lactamasse resistant penicillins?
Methicillin, nafcillin, oxacillin, cloxacillin, dicloxacillin, flucloxacillin
Which is the prototype of β-lactamase resistant penicillins?
Methicillin
What is the spectrum of β-lactamase resistant penicillins?
Same as Penicillin G but less potent
Minimal activity against gram - infections
When are β-lactamase resistant penicillins used?
Mainly with β-lactamase -producing staphylococcus like MSSA
What are the different examples of extended spectrum penicillins?
Aminopenicillins
Antipsuedomnal penicillins
What are the examples of aminopenicillins?
Ampicillin and Amoxicillin
What is the pharmacokinetics of Ampicillin?
Given orally or IV
What is the pharmacokinetics of Amoxicillin?
Given orally
What is the pharmacokinetics of Aminopenicillins?
Same as Penicillin G and have improved activity against Gram -
Less potent than Penicillin G
What happens if you add β-lactamase inhibitor?
Further extends spectrum
What are the combinations of aminopenicillins and β-lactamase inhibitor?
Amoxicillin/ Clavulanate
Ampicillin/Sulbactam
What are the examples of antipseudomonal penicillins ?
Carbepenicillin
Ticarcillin
Piparacellin
What is the spectrum of the antipseudomonal penicillins?
Same as aminopenicillins plus activity against pseudomonas, proteus, and klabsiella
What are the generalised pharmacokinetics of Penicillins?
Orally or Parenterally
Widely distributed; exhibit 45 to 68% protein-binding mainly to albumin
Penetrate inflamed meninges and reach CSF
Eliminated via kidneys –> tubular secretion
What are the adverse effects of penicillins?
Hypersensitivity reactions
GI disturbances
Cross-sensitivity to other penicillins or cephalosporins
What are some examples of therapeutic use of Penicillins?
Meningitis
Listeriosis
Endocarditi
Anaerobic LRTI
URTI
Anthrax
Gonorrhoea
Syphilis
What are examples of the β-lactamase inhibitor?
Clavulanic acid
Tazobactam
Sulbactam
Mechanism of action of β-lactamase inhibitor?
Resemble β-lactams in structure,
No significant antibacterial activity
Inhibit many β-lactamases
What is Augmentin?
Combination of β-lactamase inhibitor with hydrolazable β-lactams
Amoxicillin + Clavulanic Acid