Penicillins (PCNs or pens)
- Penicillins are among the most widely effective and the least toxic drugs known, but increased resistance has limited their use.
- Penicillin nucleus consists of fused thiazolidine and β-lactam rings to which side chains are attached through an amide linkage.
- Members of this family differ from one another in the R substituent attached to the 6-aminopenicillanic acid residue. The nature of this side chain affects the antimicrobial spectrum, stability to stomach acid, cross-hypersensitivity, and susceptibility to bacterial degradative enzymes (β-lactamases).
Penicillins are classified as following :
1. Narrow Spectrum Penicillins
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2. Extended spectrum Penicillins
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Mechanism of action :
Penicillins interfere with the synthesis of bacterial cell wall.
- The penicillins interfere with the last step of bacterial cell wall synthesis (transpeptidation or cross-linkage) by inhibiting the transpeptidases, resulting in exposure of the osmotically less stable membrane. These enzymes and related proteins constitute the penicillin binding proteins (PBPs) which have been located in the bacterial cell membrane. Each organism has several PBPs and PBPs obtained from different species differ in their affinity towards different β-lactam antibiotics. This fact probably explains their differing sensitivity to the various β-lactam antibiotics.
- Cell lysis can then occur, either through osmotic pressure or through the activation of autolysins. These drugs are bactericidal and work in a time-dependent fashion.
Penicillins are only effective against rapidly growing organisms that synthesize a peptidoglycan cell wall. Consequently, they are inactive against organisms devoid of this structure, such as mycobacteria, protozoa, fungi, and viruses.
Antibacterial spectrum :
The antibacterial spectrum of the various penicillins is determined, in part, by their ability to cross the bacterial peptidoglycan cell wall to reach the PBPs in the periplasmic space.
Factors that determine the susceptibility of PBPs to these antibiotics include the size, charge, and hydrophobicity of the particular β-lactam antibiotic.
- In general, gram have cell walls that are easily traversed by penicillin, and, therefore, in the absence of resistance, they are susceptible to these drugs.
- Gram-negative microorganisms have an outer lipopolysaccharide membrane surrounding the cell wall that presents a barrier to the water-soluble penicillins. However, gram-negative bacteria have proteins inserted in the lipopolysaccharide layer that act as water-filled channels (called porins) to permit transmembrane entry.
Penicillins are primarily active against Gram-positive microorganisms while extended spectrum penicillins are also active against many Gram-negative microorganisms.
Natural resistance to the penicillins occurs in organisms that either lack a peptidoglycan cell wall (for example, Mycoplasma pneumoniae) or have cell walls that are impermeable to the drugs.
Acquired resistance to the penicillins by plasmid-mediated β-lactamases has become a significant clinical problem. Multiplication of resistant strains leads to increased dissemination of the resistance genes.
By obtaining resistance plasmids, bacteria may acquire one or more of the following properties, thus allowing survival in the presence of β-lactam antibiotics.
- β-Lactamase activity
- Decreased permeability to the drug
- Altered PBPs
Penicillins are used for management of following :
- Streptococcal infections
- Pneumococcal infections
- Meningococcal infections
- Tetanus and gas gangrene
- Anthrax, actinomycosis, trench mouth, rat bite fever and those caused by Listeria monocytogenes, Pasteurella multocida.
Prophylactic uses for Rheumatic fever, Bacterial endocarditis, & Agranulocytosis patients.
Penicillins are among the safest drugs, and blood levels are not monitored. However, adverse reactions may occur :
- Hypersensitivity: Approximately 5% percent of patients have some kind of reaction, ranging from rashes to angioedema (marked swelling of the lips, tongue, and periorbital area) and anaphylaxis. Cross-allergic reactions occur among the β-lactam antibiotics. To determine whether treatment with a β-lactam is safe when an allergy is noted, patient history regarding severity of previous reaction is essential.
- Superinfections: Diarrhea is a common problem that is caused by a disruption of the normal balance of intestinal microorganisms. It occurs to a greater extent with those agents that are incompletely absorbed and have an extended antibacterial spectrum. Pseudomembranous colitis from Clostridium difficile and other organisms may occur with penicillin use.
- Nephritis: Penicillin, particularly methicillin, have the potential to cause acute interstitial nephritis. [Note: Methicillin is therefore no longer used clinically.]
- Neurotoxicity: The penicillins are irritating to neuronal tissue, and they can provoke seizures if injected intrathecally or if very high blood levels are reached. Epileptic patients are particularly at risk due to the ability of penicillin to cause GABAergic inhibition.
- Hematologic toxicities: Decreased coagulation may be observed with high doses of piperacillin, ticarcillin, and nafcillin (and, to some extent, with penicillin-G). Cytopenias have been associated with therapy of greater than 2 weeks, and therefore, blood counts should be monitored weekly for such patients.
Jarisch-Herxheimer reaction : Penicillin injected in a syphilitic patient (particularly secondary syphilis) may produce shivering, fever, myalgia, exacerbation of lesions, even vascular collapse. This is due to sudden release of spirochetal lytic products and lasts for 1 2-72 hours. It does not recur and does not need interruption of therapy. Aspirin and sedation afford relief of symptoms.
- Penicillin blood levels may be prolonged by concurrent administration of probenecid which blocks the renal tubular secretion of penicillins.
- Contraindicated in patients with known hypersensitivity to penicillin.
For detailed query or in case of uncertainty, Always consult your doctor or pharmacist.