AFRI PEN

Indications

• Tuberculosis
• Bacterial infections due to susceptible organisms
• Severe Gram-negative bacterial infections
• Bacterial endocarditis in specific cases

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations based on age, weight, and clinical condition.

Adults: Refer to professional guidelines for specific dosing regimens based on the type and severity of infection, renal function, and other patient-specific factors.

Mechanism of action

Dihydrostreptomycin binds to the 30S ribosomal subunit of bacteria, disrupting the translation process of mRNA into proteins. This binding causes misreading of the mRNA, leading to the production of non-functional or toxic proteins, ultimately resulting in bacterial cell death. The action of dihydrostreptomycin is concentration-dependent, meaning that higher concentrations lead to more effective bacterial killing.

Pharmacodynamics

Dihydrostreptomycin exhibits bactericidal properties, which means it kills bacteria rather than merely inhibiting their growth. The efficacy of dihydrostreptomycin is influenced by factors such as the concentration of the drug, the duration of exposure, and the susceptibility of the bacterial strain being treated. The drug's effectiveness is enhanced when used in combination with other antibiotics, particularly in the treatment of multidrug-resistant tuberculosis.

Pharmacokinetics

Dihydrostreptomycin is administered parenterally, as it is poorly absorbed from the gastrointestinal tract. After administration, it is distributed widely throughout body fluids and tissues, with a volume of distribution that is significantly higher than plasma volume. The drug is primarily excreted unchanged in the urine, and its half-life can be affected by renal function. Dose adjustments may be necessary in patients with impaired kidney function to avoid toxicity.

Contra-indications

• Hypersensitivity to dihydrostreptomycin or other aminoglycosides
• Pregnancy unless potential benefits outweigh risks
• Severe renal impairment

Adverse effects

• Ototoxicity, potentially leading to hearing loss or balance issues
• Nephrotoxicity, characterized by elevated serum creatinine or proteinuria
• Neuromuscular blockade, leading to respiratory distress
• Allergic reactions, including rash and anaphylaxis

Interactions

• Potentially increased risk of ototoxicity with other ototoxic drugs such as loop diuretics
• Increased nephrotoxicity risk when used with other nephrotoxic agents like NSAIDs
• May potentiate neuromuscular blockade when used with neuromuscular blockers

Precautions

• Monitor renal function regularly in patients with pre-existing renal impairment
• Caution in patients with myasthenia gravis or other neuromuscular disorders
• Use with caution in the elderly and very young patients

Pregnancy

Dihydrostreptomycin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, as it may cause fetal harm.

Breast-feeding

It is not known whether dihydrostreptomycin is excreted in human milk. Caution should be exercised when administering to nursing women.

Storage

Store at controlled room temperature, away from moisture and light. Keep out of reach of children.

Formulations

• Injectable solution

Indications

• Bacterial infections caused by susceptible strains
• Tuberculosis
• Brucellosis
• Certain Gram-negative bacterial infections

Dosage

Children: Refer to paediatric dosing guidelines based on the indication and patient's weight, as dosing must be individualized.

Adults: Refer to specific dosing guidelines based on the indication and severity of the infection, as dosing may vary.

Mechanism of action

Penstreptomycin works by inhibiting bacterial protein synthesis. It binds to the 30S ribosomal subunit of bacteria, leading to the misreading of mRNA and ultimately resulting in the production of nonfunctional or toxic proteins. This disruption of protein synthesis impairs bacterial growth and replication, leading to cell death.

Pharmacodynamics

The pharmacodynamic properties of penstreptomycin are characterized by its bactericidal activity against susceptible bacteria. Its efficacy is influenced by factors such as the concentration of the drug at the site of infection and the susceptibility of the bacteria. The drug has a post-antibiotic effect, meaning that its antibacterial activity may persist even after serum concentrations have fallen below the minimum inhibitory concentration (MIC).

Pharmacokinetics

Penstreptomycin is administered parenterally, as it is not well absorbed from the gastrointestinal tract. After administration, it reaches peak plasma concentrations relatively quickly. The drug is distributed throughout the body, including the kidneys and other tissues. It is primarily excreted unchanged in the urine, and its elimination half-life can vary based on renal function. In patients with impaired renal function, dosage adjustments may be necessary to prevent toxicity.

Adverse effects

• Ototoxicity
• Nephrotoxicity
• Allergic reactions
• Nausea
• Vomiting
• Rash

Interactions

• Increased risk of nephrotoxicity with other nephrotoxic agents
• Potential interaction with ototoxic drugs

Precautions

• Monitor renal function regularly during treatment
• Use with caution in patients with pre-existing hearing loss
• Assess for any history of allergic reactions to aminoglycosides

Pregnancy

Use only if clearly needed. Potential risk of fetal harm due to ototoxicity.

Breast-feeding

Caution is advised as it may be excreted in breast milk; effects on nursing infants are unknown.

Storage

Store at room temperature, away from light and moisture. Do not freeze.

Formulations

• Injectable solution