GENTANOVA

Indications

• Bacterial infections
• Sepsis
• Pneumonia
• Meningitis
• Endocarditis
• Biliary tract infections
• Prostatitis
• Surgical prophylaxis
• Acute diverticulitis
• Leg ulcer infections

Dosage

Adults: 3–5 mg/kg daily in 3 divided doses, or a single daily dose of 5–7 mg/kg adjusted according to serum-gentamicin concentration. For surgical prophylaxis, 1.5 mg/kg administered intraven

Mechanism of action

Gentamicin exerts its antibacterial effects through a multi-phase mechanism. Initially, it binds to negatively charged components of bacterial cell membranes, increasing membrane permeability. Following this, it enters the bacterial cell via energy-dependent transport mechanisms, where it binds to the 30S ribosomal subunit. This binding causes mistranslation of proteins and disrupts membrane integrity, resulting in bacterial cell death. The action is concentration-dependent, leading to rapid bactericidal effects.

Pharmacodynamics

Gentamicin has a rapid onset of action due to its mechanism of disrupting the bacterial cell membrane and inhibiting protein synthesis. Its effectiveness is enhanced by higher concentrations, and it demonstrates a post-antibiotic effect where bacteria remain suppressed even after drug levels fall below the minimum inhibitory concentration. The drug's efficacy is influenced by factors like the bacterial strain and its susceptibility patterns.

Pharmacokinetics

Gentamicin is usually administered intravenously or intramuscularly. It has a volume of distribution of approximately 0.25 L/kg and is not significantly protein-bound. The drug is primarily eliminated via renal excretion, with a half-life of 2 to 3 hours in individuals with normal renal function. Dosing adjustments are necessary in patients with renal impairment to avoid toxicity. Serum levels should be monitored to optimize therapeutic efficacy while minimizing toxicity.

Contra-indications

• Hypersensitivity to gentamicin or any aminoglycoside
• Severe renal impairment
• Pre-existing auditory or vestibular dysfunction

Adverse effects

• Ototoxicity (hearing loss, vertigo, tinnitus)
• Nephrotoxicity
• Neuromuscular blockade
• Allergic reactions (rash, pruritus)
• Injection site reactions

Interactions

• Gentamicin + relugolix: Unknown (increases exposure)
• Gentamicin + other nephrotoxic drugs (e.g., vancomycin, cisplatin): Increased risk of nephrotoxicity
• Gentamicin + neuromuscular blocking agents: Enhanced neuromuscular blockade

Precautions

• Monitor renal function during therapy, especially in patients with pre-existing renal impairment
• Caution in patients with pre-existing hearing loss or vestibular disorders
• Use with caution in pregnant women and during breastfeeding

Pregnancy

Use only if clearly needed and the benefit justifies the risk to the fetus. Limited data on use in pregnancy.

Breast-feeding

Gentamicin is excreted in breast milk, exercise caution when administering to breastfeeding mothers. Monitor infant for possible side effects.

Storage

Store below 25°C. Protect from light. Do not freeze.

Formulations

• Injection solution (various concentrations)
• Ophthalmic solution (0.3% w/v)
• Topical ointment (0.1% w/v)

Indications

• Acute poisoning
• Drug overdose
• Gastrointestinal decontamination

Dosage

Children: Refer to specific pediatric dosing recommendations based on the child's weight and the clinical situation.

Adults: Refer to specific guidelines depending on the type of poisoning and the clinical scenario.

Mechanism of action

Activated charcoal works through a process called adsorption, where toxins and drugs adhere to the surface of the charcoal particles due to electrostatic attractions and Van der Waals forces. This prevents the absorption of these substances in the gastrointestinal tract, allowing them to be excreted from the body.

Pharmacodynamics

The pharmacodynamic effects of activated charcoal are related to its ability to bind a wide range of substances. The efficacy of activated charcoal varies depending on the type and amount of the toxin or drug ingested, as well as the time elapsed since ingestion. Generally, activated charcoal is most effective when administered within one hour of ingestion of a toxic substance.

Pharmacokinetics

Activated charcoal is not absorbed by the gastrointestinal tract; instead, it remains in the gut, where it binds to ingested substances and promotes their elimination via feces. Its effects are dose-dependent, and it is typically administered as a single dose, although multiple doses may be considered in certain cases of severe poisoning.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Constipation
• Abdominal pain
• Aspiration pneumonia (if inhaled)
• Electrolyte imbalances

Precautions

• Use with caution in patients with gastrointestinal obstruction
• Monitor for potential aspiration in patients with reduced consciousness
• Consider electrolyte levels in patients with significant diarrhea or vomiting

Pregnancy

Activated charcoal is generally considered safe for use in pregnancy, but consult a healthcare professional before use.

Breast-feeding

Activated charcoal is excreted in breast milk, use with caution and consult a healthcare professional.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Activated charcoal powder
• Activated charcoal capsules
• Activated charcoal tablets

Indications

• Acute poisoning
• Drug overdose
• Gastrointestinal decontamination
• Treatment of certain types of toxin ingestion

Dosage

Children: For children over 1 year of age, the recommended dosage of activated charcoal is 1 gram per kilogram of body weight, up to a maximum of 50 grams. For children under 1 year, consult the BNF for Children for specific dosing guidance.

Adults: The usual adult dosage for activated charcoal in the treatment of poisoning is 50 to 100 grams, administered orally or via a nasogastric tube. Repeat doses may be given in certain cases, depending on the toxin involved.

Mechanism of action

Activated charcoal works primarily by adsorbing toxins and drugs in the gastrointestinal tract, reducing their systemic absorption. The extensive surface area and porous structure of activated charcoal allow it to bind various substances through van der Waals forces and hydrogen bonding. This binding action helps to prevent the absorption of harmful substances into the bloodstream, facilitating their elimination from the body.

Pharmacodynamics

The efficacy of activated charcoal is related to its ability to adsorb a wide range of substances, including many pharmaceuticals and poisons. The effectiveness can vary depending on the specific substance, the timing of administration, and the dose of activated charcoal. It is generally most effective when administered soon after ingestion of the toxin.

Pharmacokinetics

Activated charcoal is not absorbed systemically; it acts locally within the gastrointestinal tract. After administration, it passes through the gastrointestinal system and is eventually excreted in the feces. The adsorption capacity of activated charcoal is influenced by factors such as the surface area, particle size, and the nature of the toxin to which it is exposed.

Contra-indications

• Intestinal obstruction
• Gastrointestinal perforation
• Severe constipation

Adverse effects

• Gastrointestinal disturbances such as nausea and vomiting
• Constipation
• Black stools
• Aspiration pneumonia if inhaled

Interactions

• May reduce the absorption of certain medications, including anticoagulants, anticonvulsants, and others
• Should not be given simultaneously with other oral medications

Precautions

• Use with caution in patients with a history of gastrointestinal disorders
• Ensure airway protection in unconscious or compromised patients to prevent aspiration
• Monitor for potential electrolyte imbalances

Pregnancy

Charcoal is generally considered safe during pregnancy, but should only be used when necessary and under medical supervision.

Breast-feeding

Charcoal is unlikely to adversely affect a nursing infant, but should be used with caution.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Activated charcoal tablets
• Activated charcoal powder
• Activated charcoal suspension

Indications

• Lead poisoning
• Mercury poisoning
• Cadmium poisoning
• Hypercalcemia
• Diagnostic aid in certain medical tests

Dosage

Children: Refer to the BNF for Children for appropriate dosing based on the condition and age of the child.

Adults: Refer to the specific guidelines in the BNF for appropriate dosing based on the condition being treated.

Mechanism of action

EDTA2Na acts by chelating divalent and trivalent metal ions through the formation of stable, water-soluble complexes. The chelation process involves the formation of coordinate covalent bonds between the electron-rich donor atoms of EDTA and the metal ions, effectively reducing the bioavailability and toxicity of the metals. This mechanism enhances the renal excretion of the metal complexes, thus decreasing their concentration in the body.

Pharmacodynamics

The pharmacodynamic effects of EDTA2Na are primarily related to its chelating activity, leading to the reduction of metal toxicity and the alleviation of symptoms associated with heavy metal exposure. It can also influence the distribution of certain minerals and trace elements within the body, potentially affecting their physiological functions. However, its use can result in the depletion of essential minerals, necessitating careful monitoring and management during treatment.

Pharmacokinetics

EDTA2Na is administered intravenously or intramuscularly, allowing for rapid systemic distribution. It is not readily absorbed from the gastrointestinal tract, which limits its oral bioavailability. Once in the circulation, EDTA binds to metal ions and is excreted primarily via the kidneys. The half-life of EDTA varies based on the presence of chelated metals, but typically it is eliminated from the body within a few hours following administration. Renal function plays a significant role in the clearance of EDTA and its metal complexes.

Contra-indications

• Hypersensitivity to EDTA or any of its components
• Severe renal impairment
• Active bleeding disorders

Adverse effects

• Hypocalcemia
• Nausea
• Vomiting
• Diarrhea
• Fever
• Headache
• Thrombocytopenia
• Renal toxicity
• Cardiac arrhythmias

Interactions

• May enhance the effects of anticoagulants, leading to increased bleeding risk
• May interfere with the absorption of essential minerals such as calcium, magnesium, and zinc
• Caution with nephrotoxic agents due to potential additive renal toxicity

Precautions

• Use with caution in patients with renal impairment
• Monitor serum electrolytes, particularly calcium levels, during treatment
• Should not be administered rapidly due to risk of hypotension
• Not recommended for use in children unless supervised by a specialist

Pregnancy

The safety of EDTA in pregnancy has not been established. It should be used only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

EDTA is excreted in breast milk. Caution should be exercised when administered to nursing mothers.

Storage

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

Formulations

• Intravenous solution
• Intramuscular injection
• Oral tablets

Mechanism of action

There are 3 key phases of aminoglycoside entry into cells. The first “ionic binding phase” occurs when polycationic aminoglycosides bind electrostatically to negatively charged components of bacterial cell membranes including with lipopolysaccharides and phospholipids within the outer membrane of Gram-negative bacteria and to teichoic acids and phospholipids within the cell membrane of Gram-positive bacteria. This binding results in displacement of divalent cations and increased membrane permeability, allowing for aminoglycoside entry. The second “energy-dependent phase I” of aminoglycoside entry into the cytoplasm relies on the proton-motive force and allows a limited amount of aminoglycoside access to its primary intracellular target - the bacterial 30S ribosome. This ultimately results in the mistranslation of proteins and disruption of the cytoplasmic membrane. Finally, in the “energy-dependent phase II” stage, concentration-dependent bacterial killing is observed. Aminoglycoside rapidly accumulates in the cell due to the damaged cytoplasmic membrane, and protein mistranslation and synthesis inhibition is amplified. The necessity of oxygen-dependent active transport explains why aminoglycosides are ineffective against anaerobic bacteria. Hence, aminoglycosides have both immediate bactericidal effects through membrane disruption and delayed bactericidal effects through impaired protein synthesis; observed experimental data and mathematical modeling support this two-mechanism model. Inhibition of protein synthesis is a key component of aminoglycoside efficacy. Structural and cell biological studies suggest that aminoglycosides bind to the 16S rRNA in helix 44 (h44), near the A site of the 30S ribosomal subunit, altering interactions between h44 and h45. This binding also displaces two important residues, A1492 and A1493, from h44, mimicking normal conformational changes that occur with successful codon-anticodon pairing in the A site. Overall, aminoglycoside binding has several negative effects including inhibition of translation, initiation, elongation, and ribosome recycling. Recent evidence suggests that the latter effect is due to a cryptic second binding site situated in h69 of the 23S rRNA of the 50S ribosomal subunit. Also, by stabilizing a conformation that mimics correct codon-anticodon pairing, aminoglycosides promote error-prone translation. Mistranslated proteins can incorporate into the cell membrane, inducing the damage discussed above. Aminoglycosides are usually bactericidal in action. Although the exact mechanism of action has not been fully elucidated, the drugs appear to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits. /Aminoglycosides/ ... Aminoglycosides are aminocyclitols that kill bacteria by inhibiting protein synthesis as they bind to the 16S rRNA and by disrupting the integrity of bacterial cell membrane. Aminoglycoside resistance mechanisms include: (a) the deactivation of aminoglycosides by N-acetylation, adenylylation or O-phosphorylation, (b) the reduction of the intracellular concentration of aminoglycosides by changes in outer membrane permeability, decreased inner membrane transport, active efflux, and drug trapping, (c) the alteration of the 30S ribosomal subunit target by mutation, and (d) methylation of the aminoglycoside binding site. ... /Aminoglycosides/