APDROPS

Indications

• Bacterial infections
• Complicated skin and soft-tissue infections
• Pelvic inflammatory disease
• Respiratory tract infections
• Intra-abdominal infections

Dosage

Children: Refer to the BNF for Children for appropriate dosing information.

Adults: 400 mg once daily for 7-21 days, depending on the specific infection being treated.

Mechanism of action

Moxifloxacin's bactericidal effect is primarily due to its inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV. By interfering with these enzymes, moxifloxacin prevents the replication, transcription, and repair of bacterial DNA. This mechanism is crucial for bacterial cell division and survival.

Pharmacodynamics

As a quinolone antibiotic, moxifloxacin is effective against a range of bacteria including aerobic Gram-positive organisms such as _Staphylococcus aureus_ and _Streptococcus pneumoniae_, as well as Gram-negative organisms like _Haemophilus influenzae_. It is known for its high affinity for bacterial DNA gyrase, which is approximately 100 times greater than its affinity for mammalian enzymes, making it selectively toxic to bacteria.

Pharmacokinetics

Moxifloxacin exhibits good oral bioavailability and is widely distributed in body tissues, reaching peak plasma concentrations approximately 1 to 2 hours after administration. The drug is primarily metabolized in the liver and excreted via the urine. The half-life of moxifloxacin is approximately 12 hours, allowing for once-daily dosing.

Contra-indications

• Acute myocardial infarction (risk factor for QT interval prolongation)
• Bradycardia (risk factor for QT interval prolongation)
• Congenital long QT syndrome (risk factor for QT interval prolongation)
• Electrolyte disturbances (risk factor for QT interval prolongation)
• Heart failure with reduced left ventricular ejection fraction (risk factor for QT interval prolongation)
• History of symptomatic arrhythmias (risk factor for QT interval prolongation)

Adverse effects

• Increased risk of infection
• Akathisia
• Angina pectoris
• Colitis associated with antibiotics
• Asthma
• Dehydration
• Gastritis
• Hyperlipidaemia
• Malaise
• Oedema
• Pelvic pain
• Thrombocytosis
• Vasodilation

Precautions

• May impair performance of skilled tasks (e.g. driving)
• Use with caution in patients with a history of seizures or CNS disorders

Pregnancy

Manufacturer advises use only if potential benefit outweighs risk.

Breast-feeding

Manufacturer advises avoid-present in milk in animal studies.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Tablets 400 mg
• Injection solution 400 mg/250 ml
• Nebuliser solution 100 mg/1 ml

Indications

• Topical antifungal treatment
• Treatment of yeast infections
• Disinfectant for minor cuts and abrasions

Dosage

Children: Refer to specific product guidelines or medical literature as dosages can vary based on formulation and indication.

Adults: Refer to specific product guidelines or medical literature as dosages can vary based on formulation and indication.

Mechanism of action

Information regarding the mechanism of action of boric acid in mediating its antibacterial or antifungal actions is limited. Boric acid inhibits biofilm formation and hyphal transformation of Candida albicans, which are critical virulence factors. In addition, arrest of fungal growth was observed with the treatment of boric acid.

Pharmacodynamics

Boric acid exhibits minimal bacteriostatic and antifungal activities. It is likely to mediate antifungal actions at high concentrations over prolonged exposures. The effectiveness of boric acid as a topical agent depends on the concentration and duration of exposure to the target organism.

Pharmacokinetics

The pharmacokinetics of borax are not extensively documented. However, it is known that borax is poorly absorbed when ingested orally, and its effects are primarily local when applied topically. Systemic absorption can occur, but this is generally minimal. Boron, the active component in borax, may accumulate in body tissues with prolonged exposure, although specific details regarding the distribution, metabolism, and excretion of borax remain limited.

Pregnancy

Boric acid should be used with caution during pregnancy. Consult a healthcare professional before use.

Breast-feeding

Use of boric acid while breastfeeding is not well established. Consult a healthcare professional.

Storage

Store in a cool, dry place, protected from light. Keep out of reach of children.

Indications

• Vulvovaginal candidiasis
• Fungal infections
• Antiseptic for minor cuts and abrasions
• Ocular antiseptic
• Insecticide in pest control

Dosage

Adults: Refer to specific guidelines for formulations. Commonly used as a 2-3% solution

Mechanism of action

Boric acid exerts its antifungal effects by disrupting the cell membrane integrity of fungi. It interferes with the synthesis of essential cellular components, leading to cell lysis and death. The acid also has mild antibacterial properties, which can help in reducing bacterial load in infected areas. The exact molecular pathways involved in these actions are not fully elucidated, but it is known to alter the pH of the environment, making it less conducive for fungal growth.

Pharmacodynamics

Boric acid demonstrates a low toxicity profile in humans when used appropriately. Its antifungal activity is primarily effective against Candida species, and it can be used as a second-line treatment for vulvovaginal candidiasis, particularly in cases of recurrent infections. The effectiveness of boric acid is also attributed to its ability to maintain an acidic environment, which is unfavorable for the growth of many pathogens. Its antiseptic properties help in reducing inflammation and promoting healing in infected tissues.

Pharmacokinetics

Boric acid is poorly absorbed through the gastrointestinal tract but can be absorbed through the skin and mucous membranes. Once absorbed, it is distributed throughout the body, with a tendency to accumulate in various tissues, including the liver and kidneys. The elimination half-life of boric acid is variable, depending on dosage and route of administration. It is primarily excreted unchanged in the urine. Due to its potential for toxicity with high systemic exposure, it is important to adhere to recommended dosages.

Contra-indications

• Hypersensitivity to boron or any component of the formulation
• Severe renal impairment

Adverse effects

• Skin irritation or rash
• Nausea
• Vomiting
• Diarrhea
• Headache
• Fatigue
• Tremors
• Confusion

Interactions

• May interact with other topical medications
• Caution with nephrotoxic agents

Precautions

• Use with caution in patients with renal insufficiency
• Careful monitoring is advised in long-term use
• Not recommended for use in large areas of broken skin

Pregnancy

Boric acid is classified as category C. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Limited data available. It is advisable to avoid use while breastfeeding.

Storage

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

Formulations

• Topical ointment
• Powder
• Solution

Mechanism of action

Information regarding the mechanism of action of boric acid in mediating its antibacterial or antifungal actions is limited. Boric acid inhibits biofilm formation and hyphal transformation of _Candida albicans_, which are critical virulence factors. In addition, arrest of fungal growth was observed with the treatment of boric acid.

Pharmacodynamics

Boric acid exhibits minimal bacteriostatic and antifungal activities. Boric acid is likely to mediate antifungal actions at high concentrations over prolonged exposures.

Mechanism of action

The bactericidal action of moxifloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV. DNA gyrase is an essential enzyme that is involved in the replication, transcription and repair of bacterial DNA. Topoisomerase IV is an enzyme known to play a key role in the partitioning of the chromosomal DNA during bacterial cell division. The fluoroquinolone antibiotic moxifloxacin has been associated with the acquired long QT syndrome and is used as a positive control in the evaluation of the QT-interval prolonging potential of new drugs. In common with other QT-prolonging agents, moxifloxacin is known to inhibit the hERG potassium K+ channel, but at present there is little mechanistic information available on this action. This study was conducted in order to characterise the inhibition of hERG current (I(hERG)) by moxifloxacin, and to determine the role in drug binding of the S6 aromatic amino-acid residues Tyr652 and Phe656. hERG currents were studied using whole-cell patch clamp (at room temperature and at 35-37 degrees C) in an HEK293 cell line stably expressing hERG channels. Moxifloxacin reversibly inhibited currents in a dose-dependent manner. We investigated the effects of different voltage commands to elicit hERG currents on moxifloxacin potency. Using a 'step-ramp' protocol, the IC50 was 65 uM at room temperature and 29 microM at 35 degrees C. When a ventricular action potential waveform was used to elicit currents, the IC50 was 114 microM. Block of hERG by moxifloxacin was found to be voltage-dependent, occurred rapidly and was independent of stimulation frequency. Mutagenesis of the S6 helix residue Phe656 to Ala failed to eliminate or reduce the moxifloxacin-mediated block whereas mutation of Tyr652 to Ala reduced moxifloxacin block by approximately 66%. Our data demonstrate that moxifloxacin blocks the hERG channel with a preference for the activated channel state. The Tyr652 but not Phe656 S6 residue is involved in moxifloxacin block of hERG, concordant with an interaction in the channel inner cavity. The bactericidal action of moxifloxacin results from inhibition of the topoisomerase II (DNA gyrase) and topoisomerase IV required for bacterial DNA replication, transcription, repair, and recombination. It appears that the C8-methoxy moiety contributes to enhanced activity and lower selection of resistant mutants of Gram-positive bacteria compared to the C8-H moiety. The presence of the bulky bicycloamine substituent at the C-7 position prevents active efflux, associated with the NorA or pmrA genes seen in certain Gram-positive bacteria. Torsade de pointes (TdP) is increasingly recognized as a complication of drug therapy. The most common cause of drug-induced QT prolongation is inhibition of the rapidly activating component of the delayed potassium current (I(Kr)). Moxifloxacin, a widely used fluoroquinolone, is a weak I(Kr) inhibitor and has been associated with QT prolongation. Fluoroquinolones prolong the QT interval by blocking voltage-gated potassium channels, especially the rapid component of the delayed rectifier potassium current I(Kr), expressed by HERG (the human ether-a-go-go-related gene). According to the available case reports and clinical studies, moxifloxacin carries the greatest risk of QT prolongation from all available quinolones in clinical practice and it should be used with caution in patients with predisposing factors for Torsades de pointes (TdP).

Pharmacodynamics

Moxifloxacin is a quinolone/fluoroquinolone antibiotic. Moxifloxacin can be used to treat infections caused by the following bacteria: Aerobic Gram-positive microorganisms: _Corynebacterium_ species, _Micrococcus luteus_, _Staphylococcus aureus_, _Staphylococcus epidermidis_, _Staphylococcus haemolyticus_, _Staphylococcus hominis_, _Staphylococcus warneri_, _Streptococcus pneumoniae_, and _Streptococcus viridans_ group. Aerobic Gram-negative microorganisms: _Acinetobacter lwoffii_, _Haemophilus influenzae_, and _Haemophilus parainfluenzae_. Other microorganisms: _Chlamydia trachomatis_. Moxifloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian. Moxifloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria.