PENIREN TABLETS

Indications

• Bacterial infections
• Streptococcal pharyngitis
• Otitis media
• Skin infections
• Prevention of rheumatic fever
• Prevention of secondary cases of invasive group A streptococcal infection

Dosage

Adults: 500 mg every 6 hours, increased if necessary up to 1 g every 6 hours; for urgent transfer to hospital, administer 1.2 g as a single dose prior to transfer

Mechanism of action

Phenoxymethylpenicillin inhibits the biosynthesis of cell wall mucopeptide by binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall. This binding is critical for cell wall synthesis and maintenance, leading to cell lysis as the bacterial cell wall integrity is compromised. The drug interferes with the synthesis of N-acetylmuramic acid mucopeptides and teichoic acids, essential components of the bacterial cell wall.

Pharmacodynamics

Phenoxymethylpenicillin exhibits bactericidal effects against a variety of bacteria by targeting their cell wall synthesis. It is effective against penicillin-sensitive strains of staphylococci (excluding penicillinase-producing strains), several groups of streptococci, and other specific bacteria such as Corynebacterium diphtheriae and Listeria monocytogenes. Its efficacy is particularly pronounced during the active multiplication of bacteria.

Pharmacokinetics

Phenoxymethylpenicillin is well absorbed from the gastrointestinal tract when taken orally, with peak plasma concentrations occurring within 1-2 hours after ingestion. The drug is distributed widely throughout body tissues and fluids, although penetration into the CNS is limited. It is primarily eliminated by renal excretion, with a half-life of approximately 30-60 minutes in healthy individuals. Dosage adjustments may be necessary for patients with renal impairment due to the risk of accumulation.

Adverse effects

• Jarisch-Herxheimer reaction
• Neurotoxicity
• Coma

Precautions

• Accumulation of sodium from injection can occur with high doses
• Caution in renal impairment due to risk of neurotoxicity

Pregnancy

Not known to be harmful.

Breast-feeding

Trace amounts in milk, but appropriate doses are considered safe.

Storage

Store at room temperature, protected from light. Keep out of reach of children.

Formulations

• Oral suspension
• Tablets
• Injection

Mechanism of action

Phenoxymethylpenicillin inhibits the biosynthesis of cell wall mucopeptide by binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, which are critical in the cell wall synthesis and maintenance, as well as cell division. This disrupts the third and last stage of bacterial cell wall synthesis. This subsequently leads to cell lysis. Penicillins and breakdown products of penicillins act as haptens after their covalent reaction with proteins. The most important antigenic intermediate of penicillin appears to be the penicilloyl moiety, which is formed when the beta-lactam ring is opened. This is considered to be the major (predominant) determinant of penicillin allergy. /Penicillins/ Penicillin is known to interfere with synthesis of N-acetylmuramic acid mucopeptides and teichoic acids which are part of cell-wall material. ... Under favorable conditions penicillin exerts direct bactericidal action, & successful penicillin therapy may be relatively independent of immunity mechanisms of the host. /Penicillins/ The penicillins and their metabolites are potent immunogens because of their ability to combine with proteins and act as haptens for acute antibody-mediated reactions. The most frequent (about 95 percent) or "major" determinant of penicillin allergy is the penicilloyl determinant produced by opening the beta-lactam ring of the penicillin. This allows linkage of the penicillin to protein at the amide group. "Minor" determinants (less frequent) are the other metabolites formed, including native penicillin and penicilloic acids. /Penicillins/ Bactericidal; inhibit bacterial cell wall synthesis. Action is dependent on the ability of penicillins to reach and bind penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. Penicillin-binding proteins (which include transpeptidases, carboxypeptidases, and endopeptidases) are enzymes that are involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Penicillins bind to, and inactivate, penicillin-binding proteins, resulting in the weakening of the bacterial cell wall and lysis. /Penicillins/

Pharmacodynamics

Phenoxymethylpenicillin works against penicillin-sensitive microorganisms with bactericidal effects. It targets the bacteria during its active multiplication stage by interfering with bacterial cell wall peptidoglycan synthesis. _In vitro_, phenoxymethylpenicillin was shown to be active against staphylococci (except penicillinase-producing strains), streptococci (groups A, C, G, H, L and M), and pneumococci, as well as _Corynebacterium diphtheriae_, _Bacillus anthracis_, Clostridia, _Actinomyces bovis_, _Streptobacillus moniliformis_, _Listeria monocytogenes_, _Leptospira_, _Neisseria gonorrhoeae_, and _Treponema pallidum_.