Certain antimicrobial medications specifically disrupt the creation of bacterial cell walls, a feature absent in mammalian cells. These cell walls are constructed from a substance called peptidoglycan, made up of glycan units linked together by peptide cross-links. To work optimally, inhibitors of cell wall synthesis need to target actively multiplying microorganism.
Structure of pencillins
Penicillins have a core structure comprising a four-membered B-lactam ring linked to a thiazolidine ring and an R side chain. Variations within this family arise from differences in the R group attached to the 6-aminopenicillanic acid residue. This side chain influences factors such as the spectrum of antimicrobial activity, resistance to stomach acid, cross-reactivity, and vulnerability to bacterial enzymes (B-lactamases).
Mechanism of action
In terms of mechanism, penicillins disrupt the final stage of bacterial cell wall synthesis, namely the cross-linking of adjacent peptidoglycan strands through transpeptidation. Structurally resembling the end of the peptidoglycan strand, penicillins compete with it and bind to penicillin-binding proteins (PBPs). These enzymes, which catalyze transpeptidase, are crucial for cross-linking the cell wall. Consequently, the weakened cell wall leads to cell death, rendering penicillins bactericidal and operating in a time-dependent manner.
Range of spectrum
The range of bacteria susceptible to penicillins depends partly on their ability to penetrate the bacterial peptidoglycan cell wall to access PBPs in the periplasmic space. Factors influencing PBP susceptibility to these antibiotics include their size, charge, and hydrophobicity.
Drugs included
Amoxicillin
Brand name :AMOXIL
Ampicillin
Dicloxacillin
Nafcillin
Oxacillin
Penicillin G
Brand name :PFIZERPEN
Penicillin G benzathine
Brand name :BICILLIN L-A
Penicillin G benzathine and penicillin
G procaine
Brand name :BICILLIN C-R
Penicillin V
Susceptible organisms
Gram (+) cocci
Streptococcus pneumoniae*
Streptococcus pyogenes
Viridans streptococci* group
Gram (+) bacilli
Bacillus anthracis
Corynebacterium diphtheriae
Gram (-) cocci
Neisseria gonorrhoeae
Neisseria meningitidis
Gram (-) rods
Anaerobic organisms
Clostridium perfringens
Spirochetes
Treponema pallidum (syphilis)
Treponema pertenue (yaws)
Mycoplasmas
Chlamydia
Resistance
Their resistance develops due to beta lactamase production , decreased permeability to drug and alterations in penicillin binding proteins .
Pharmacokinetics of Penicillins:
- Administration: The choice of administration route for β-lactam antibiotics depends on their stability to gastric acid and the seriousness of the infection.
Natural Penicillins:
– Penicillin V
– Antistaphylococcal Penicillins: Methicillin, Nafcillin, Oxacillin
- Routes of Administration: Certain combinations like ampicillin with sulbactam, piperacillin with tazobactam, and antistaphylococcal penicillins (nafcillin, oxacillin) are given intravenously or intramuscularly. Penicillin V, amoxicillin, and dicloxacillin are oral. Others can be given orally, intravenously, or intramuscularly.
Extended Spectrum:
– Ampicillin
– Amoxicillin
– Amoxicillin clavulanate
– Ampicillin sulbactam
Antipseudomonal:
– Piperacillin
– Piperacillin tazobactam
- Depot Forms: Benzathine penicillin G and procaine penicillin G are injected intramuscularly, acting as depot forms with slow absorption and long-lasting effects.
- Absorption: The acidic environment of the intestines hampers penicillin absorption. Only a fraction of oral penicillin V is absorbed, and food slows absorption, especially for dicloxacillin. It’s best to take this medication on an empty stomach because it’s stable in acidic conditions and is easily absorbed by the body.
- Distribution :These antibiotics are well-distributed throughout the body, crossing the placental barrier without causing birth defects. However, they may not reach effective levels in certain tissues like bone or cerebrospinal fluid unless there’s inflammation. Inflamed meninges allow for better penetration of the antibiotics into the cerebrospinal fluid. They’re generally ineffective against prostate infections due to low levels reaching that area.
- Metabolism Normally, the body doesn’t metabolize these antibiotics much, except in patients with kidney issues. Nafcillin and oxacillin are exceptions as they’re primarily metabolized in the liver.
- Excretion:The main way these antibiotics are excreted is through the kidney’s organic acid secretory system and filtration. Patients with kidney problems need dosage adjustments. Nafcillin and oxacillin, metabolized in the liver, don’t need dosage adjustments for kidney issues. Probenecid can increase blood levels of these antibiotics by inhibiting their secretion in the kidney. They’re also excreted in breast milk.
Adverse effects
Hypersensitivity
Diarrhea
Neurotoxicity
Nephritis
Hematologic toxicities
Conclusion
In conclusion, penicillins and other cell wall synthesis inhibitors are vital antibiotics that disrupt bacterial cell wall formation, ultimately leading to cell death. Their mechanism of action involves binding to penicillin-binding proteins, interfering with the cross-linking of peptidoglycan strands. This renders them bactericidal against a range of susceptible organisms. While effective, resistance can develop through various mechanisms.
The pharmacokinetics of penicillins vary depending on the specific drug, with different routes of administration and absorption characteristics. They distribute well throughout the body but may require dose adjustments in patients with renal or hepatic impairment. Adverse effects such as hypersensitivity reactions, gastrointestinal disturbances, and neurological or renal toxicity can occur, necessitating careful monitoring during therapy.
Overall, understanding the pharmacology and spectrum of activity of penicillins is crucial for optimizing their clinical use while minimizing adverse effects and combating resistance.
