UROFLAV-D TABLETS

Indications

• Bacterial infections
• Complicated urinary-tract infections
• Lower respiratory-tract infections
• Skin infections
• Gonorrhoea
• Pelvic inflammatory disease
• Prostatitis
• Acute pyelonephritis

Dosage

Children: Refer to the BNF for Children for specific dosing guidance.

Adults: 200–400 mg daily for 3 days for uncomplicated urinary-tract infections; for severe or complicated infections, the dose may be increased to 400 mg twice daily for 7–10 days. In cases of renal impairment, the dose should be adjusted based on creatinine clearance.

Mechanism of action

Ofloxacin acts by inhibiting bacterial DNA gyrase and topoisomerase IV, enzymes crucial for DNA replication and transcription. This inhibition prevents normal cell division, leading to cell death. Ofloxacin has a significantly higher affinity for bacterial DNA gyrase compared to mammalian enzymes, making it effective against infectious pathogens.

Pharmacodynamics

As a quinolone antibiotic, ofloxacin demonstrates bactericidal activity, meaning it kills bacteria rather than merely inhibiting their growth. Its mechanism is primarily through the disruption of DNA supercoiling, a vital process for bacterial cell division and viability. The drug's broad-spectrum activity allows it to target a wide variety of bacterial pathogens, enhancing its utility in clinical settings.

Pharmacokinetics

Ofloxacin is well-absorbed after oral administration, with a bioavailability of approximately 98%. It is primarily metabolized in the liver and excreted through the kidneys, necessitating caution in patients with hepatic or renal impairment. The elimination half-life is about 4 to 7 hours, which supports twice-daily dosing for effective therapeutic levels.

Contra-indications

• Hypersensitivity to ofloxacin or other quinolones
• History of tendon disorders related to fluoroquinolone use
• Severe hepatic impairment
• History of QT interval prolongation
• Concurrent use of drugs that prolong the QT interval

Adverse effects

• Nausea
• Diarrhea
• Headache
• Dizziness
• Tendonitis and tendon rupture
• QT interval prolongation
• Photosensitivity
• Rash
• Anaphylaxis

Interactions

• Antacids containing magnesium or aluminum (may reduce absorption)
• Cationic drugs (e.g., iron salts, sucralfate)
• Warfarin (may enhance anticoagulant effect)
• Drugs that prolong the QT interval (e.g., class IA and III antiarrhythmics)

Precautions

• Use with caution in patients with a history of seizures or CNS disorders
• Monitor for signs of tendon damage
• Assess renal function prior to dosing, especially in elderly patients
• Caution in patients with a history of myasthenia gravis

Pregnancy

Manufacturer advises use only if the benefit outweighs the risk, as systemic quinolones have been associated with risks during pregnancy.

Breast-feeding

Ofloxacin is excreted in breast milk; caution is advised when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Protect from light.

Formulations

• 200 mg tablets
• 400 mg tablets
• Injectable solution (200 mg in 100 mL)
• Eye drops (0.3% solution)

Indications

• Urinary frequency
• Urinary urgency
• Urge incontinence
• Dysuria
• Bladder spasm due to catheterisation or surgery

Dosage

Adults: 4 mg once daily, increased if necessary up to 8 mg once daily. For specific conditions like dysuria, 200 mg three times a day is recommended, with adjustments for hepatic or renal impairment.

Mechanism of action

Flavoxate hydrochloride acts as a muscarinic antagonist, inhibiting the action of acetylcholine on muscarinic receptors in the bladder. This reduces the involuntary contractions of the bladder muscle, leading to decreased urinary urgency and frequency. It is believed to have a local anesthetic effect on the bladder wall as well, which may contribute to its symptomatic relief.

Pharmacodynamics

Flavoxate exhibits a dose-dependent reduction in bladder muscle tone and spasticity. The drug's mechanism helps to relax the detrusor muscle, thus alleviating urgency and incontinence. Its anticholinergic effects also contribute to its efficacy in reducing bladder spasms.

Pharmacokinetics

Flavoxate is well-absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 1-2 hours after oral administration. It undergoes hepatic metabolism, and its elimination half-life is approximately 5-7 hours. The drug is excreted primarily in urine, and caution is advised in patients with hepatic or renal impairment due to altered drug clearance.

Contra-indications

• Gastro-intestinal haemorrhage
• Hypersensitivity to flavoxate hydrochloride

Adverse effects

• Abdominal pain
• Dry eye
• Nasal congestion
• Asthenia
• Bladder pain
• Cough
• Diarrhoea
• Dyspnoea
• Erectile dysfunction
• Flatulence
• Hyperhidrosis
• Hypertension
• Increased risk of infection
• Insomnia
• Oedema
• Oral ulceration
• Taste altered

Interactions

• CYP3A4 inhibitors may increase exposure to flavoxate hydrochloride
• Concurrent use with potent inhibitors of CYP3A4 is not recommended in patients with hepatic or renal impairment

Precautions

• Caution in patients with hepatic impairment
• Avoid in severe hepatic impairment
• Caution in patients with renal impairment

Pregnancy

Manufacturer advises avoiding use due to potential toxicity observed in animal studies.

Breast-feeding

Present in milk in animal studies; manufacturer advises caution.

Storage

Store in a cool, dry place away from light.

Formulations

• Flavoxate hydrochloride 200 mg tablets

Indications

• Overactive bladder
• Urge urinary incontinence
• Urinary urgency
• Frequent urination

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Flavoxate acts as a direct antagonist at muscarinic acetylcholine receptors in cholinergically innervated organs. Its anticholinergic-parasympatholytic action reduces the tonus of smooth muscle in the bladder, effectively reducing the number of required voids, urge incontinence episodes, and urge severity, while improving retention and facilitating increased volume per void.

Pharmacodynamics

Flavoxate is a competitive muscarinic receptor antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. It relaxes the smooth muscle in the urinary tract, contributing to its spasmolytic effects. Muscarinic receptors are crucial for cholinergically mediated functions, including bladder contractions and salivary secretion.

Pharmacokinetics

Flavoxate is absorbed after oral administration and exhibits significant binding to plasma proteins. The drug undergoes hepatic metabolism, resulting in various metabolites. The elimination half-life can vary, and it is primarily excreted in the urine, making renal function an important consideration for dosing.

Adverse effects

• Dry mouth
• Dizziness
• Nausea
• Constipation
• Blurred vision

Interactions

• clozapine+flavoxate: Unknown (additive effect)
• antipsychotics, second generation+flavoxate: Unknown (additive effect)

Precautions

• Use with caution in patients with glaucoma
• Caution in patients with myasthenia gravis
• Monitor for urinary retention

Pregnancy

Flavoxate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Flavoxate is excreted in breast milk, caution is advised when administered to nursing women.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Tablets
• Extended-release tablets

Mechanism of action

Flavoxate acts as a direct antagonist at muscarinic acetylcholine receptors in cholinergically innervated organs. Its anticholinergic-parasympatholytic action reduces the tonus of smooth muscle in the bladder, effectively reducing the number of required voids, urge incontinence episodes, urge severity and improving retention, facilitating increased volume per void.

Pharmacodynamics

Flavoxate is a spasmolytic flavone derivative that acts by relaxing the smooth muscle in the urinary tract. Flavoxate is a competitive muscarinic receptor antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. Muscarinic receptors play an important role in several major cholin-ergically mediated functions, including contractions of urinary bladder smooth muscle and stimulation of salivary secretion.

Mechanism of action

Ofloxacin acts on DNA gyrase and toposiomerase IV, enzymes which, like human topoisomerase, prevents the excessive supercoiling of DNA during replication or transcription. By inhibiting their function, the drug thereby inhibits normal cell division. Quinolone(s) (QNs) is widely used in infection therapy due to its good antimicrobial characteristics. However, QNs-induced arthropathy of immature animals has led to restrictions on the therapeutic use of these antimicrobial agents. The exact mechanism(s) of QNs-induced chondrotoxicity remain unknown. In the present study, .../the authors/ investigated the possible mechanism of ofloxacin (one typical QNs)-induced injuries of chondrocytes. Juvenile rabbit joint chondrocytes cultured in alginate microspheres were incubated with ofloxacin at concentrations of 0, 2, 5, 10, 20, and 40 microg/mL for up to 96 hr. Concentration of 10 microg/mL ofloxacin induced apoptosis of chondrocyte with visible apoptotic signs, including degradation of poly(ADP-ribose) polymerase, caspase-3 activation, and DNA ladder formation. Furthermore, extracellular signal-regulated kinase 1/2 (phospho-ERK1/2) and growth factor receptor-bound protein 2 (Grb2) were significantly reduced, and similar changes were also observed in the beta(1)-integrin receptor as assessed by immunoblotting. However, the mRNA level of beta(1)-integrin obtained from reverse transcription-polymerase chain reaction remained unchanged. Results of beta(1)-integrin immunoprecipitation have also shown that beta(1)-integrin did not interact with activated intracellular signaling proteins. In addition, ofloxacin did not induce apoptosis and decrease beta(1)-integrin expression in chondrocytes supplemented with Mg(2+), and the ofloxacin-induced apoptosis was caspase-8-dependent, inhibition of which did not affect the expression mode of phospho-ERK1/2 and beta(1)-integrin. Our results demonstrate that ofloxacin affects beta(1)-integrin receptor functions and the ERK mitogen-activated protein kinase signaling pathway, causing caspase-8-dependent apoptosis after exposure of 48 hr. Quinolones are widely used in infection therapy due to their good antimicrobial characteristics. However, there potential joint chondrotoxicity on immature animals has stood in the way of the therapeutic application of these agents, the exact mechanism of which is still unclear. This study was undertaken to investigate the role of oxidative damage in ofloxacin (one typical quinolones)-induced arthropathy. Chondrocytes from juvenile rabbit joints were incubated with ofloxacin at concentrations of 0, 5, 10, 20, 40 and 80 ug/mL, respectively. The extent of oxidative damage was assessed by measuring the reactive oxygen species level, activities of antioxidant enzymes, and oxidative damage to some macromolecules. It was observed that ofloxacin induced a concentration-dependent increase in intracellular reactive oxygen species production, which may be an early mediator of ofloxacin cytotoxicity. Similarly, ofloxacin resulted in a significant lipid peroxidation, revealed by a concentration-dependent increase in the level of thiobarbituric acid reactive substances. At the same time, ofloxacin induced DNA damage in a concentration-dependent manner for 24 hr measured by comet assay, which may be a cause for overproduction of reactive oxygen species. Furthermore, antioxidant enzyme activities, such as glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD), were rapidly decreased after treatment with ofloxacin. In addition, SOD decline and reactive oxygen species production were strongly inhibited, and the loss in cell viability was partly abated by additional glutathione (GSH), N-acetylcysteine (NAC) and dithiothreitol (DTT). In conclusion, these results clearly demonstrated that ofloxacin could induce oxidative stress, lipid peroxidation and DNA oxidative damage to chondrocytes. Ofloxacin is a quinolone antimicrobial agent. The mechanism of action of ofloxacin and o

Pharmacodynamics

Ofloxacin is a quinolone/fluoroquinolone antibiotic. Ofloxacin 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. Ofloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria.