CIPRONAT 500 MG TABLETS

Indications

• Urinary tract infections
• Respiratory tract infections
• Skin infections
• Gastrointestinal infections
• Bone and joint infections
• Intra-abdominal infections

Dosage

Adults: Refer to the BNF for specific dosing guidelines, as doses may vary based on the type

Mechanism of action

Ciprofloxacin acts on bacterial topoisomerase II (DNA gyrase) and topoisomerase IV. By targeting the alpha subunits of DNA gyrase, it prevents the supercoiling of bacterial DNA, thereby inhibiting DNA replication. This mechanism leads to the death of susceptible organisms, although the precise pathway of how this occurs has not been fully elucidated. Ciprofloxacin demonstrates bactericidal activity during both the logarithmic and stationary phases of bacterial growth, particularly against Escherichia coli and Pseudomonas aeruginosa.

Pharmacodynamics

Ciprofloxacin is known for its high affinity for bacterial DNA gyrase, binding with 100 times the affinity of mammalian DNA gyrase. This selectivity allows it to effectively inhibit bacterial growth without significantly affecting human cells. There is no cross-resistance between fluoroquinolones and other classes of antibiotics, making ciprofloxacin a valuable option when other antibiotics fail. Research is ongoing into its potential applications against diseases such as malaria, cancers, and AIDS.

Pharmacokinetics

Ciprofloxacin is well-absorbed following oral administration, with peak plasma concentrations occurring within 1-2 hours. It has a bioavailability of approximately 70-80%. The drug is widely distributed throughout the body, including into tissues and fluids. Ciprofloxacin is primarily eliminated via renal excretion, with about 40-50% of the drug being excreted unchanged in urine. Its half-life ranges from 3 to 5 hours in healthy adults, which may be prolonged in individuals with renal impairment.

Contra-indications

• Hypersensitivity to ciprofloxacin or any of its components
• History of tendon disorders related to fluoroquinolone use
• Concurrent use of tizanidine

Adverse effects

• Nausea
• Diarrhea
• Dizziness
• Headache
• Tendon rupture or tendinopathy
• Photosensitivity reactions
• QT interval prolongation
• CNS effects including seizures

Interactions

• Antacids containing magnesium or aluminum may reduce absorption
• Iron and zinc supplements may decrease ciprofloxacin bioavailability
• Warfarin may have increased anticoagulant effect when used with ciprofloxacin
• Concurrent use with drugs that prolong the QT interval may increase risk of arrhythmias

Precautions

• Use with caution in patients with renal impairment
• Monitor blood glucose levels in diabetic patients as ciprofloxacin may cause hypoglycemia
• Caution in patients with a history of myasthenia gravis due to potential exacerbation
• Hydration is recommended to prevent crystalluria

Pregnancy

Ciprofloxacin is not recommended during pregnancy due to potential risk of arthropathy in the developing fetus.

Breast-feeding

Ciprofloxacin 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

• Oral tablets
• Oral suspension
• Intravenous infusion

Mechanism of action

Ciprofloxacin acts on bacterial topoisomerase II (DNA gyrase) and topoisomerase IV. Ciprofloxacin's targeting of the alpha subunits of DNA gyrase prevents it from supercoiling the bacterial DNA which prevents DNA replication. The mechanism by which ciprofloxacin's inhibition of DNA gyrase or topoisomerase IV results in death in susceptible organisms has not been fully determined. Unlike beta-lactam anti-infectives, which are most active against susceptible bacteria when they are in the logarithmic phase of growth, studies using Escherichia coli and Pseudomonas aeruginosa indicate that ciprofloxacin can be bactericidal during both logarithmic and stationary phases of growth; this effect does not appear to occur with gram-positive bacteria (e.g., Staphylococcus aureus). In vitro studies indicate that ciprofloxacin concentrations that approximate the minimum inhibitory concentration (MIC) of the drug induce filamentation in susceptible organisms; high concentrations of the drug result in enlarged or elongated cells that may not be extensively filamented. Although the bactericidal effect of some fluoroquinolones (e.g., norfloxacin) evidently requires competent RNA and protein synthesis in the bacterial cell, and concurrent use of anti-infectives that affect protein synthesis (e.g., chloramphenicol, tetracyclines) or RNA synthesis (e.g., rifampin) inhibit the in vitro bactericidal activity of these drugs, the bactericidal effect of ciprofloxacin is only partially reduced in the presence of these anti-infectives. This suggests that ciprofloxacin has an additional mechanism of action that is independent of RNA and protein synthesis. Ciprofloxacin usually is bactericidal in action. Like other fluoroquinolone anti-infectives, ciprofloxacin inhibits DNA synthesis in susceptible organisms via inhibition of the enzymatic activities of 2 members of the DNA topoisomerase class of enzymes, DNA gyrase and topoisomerase IV. DNA gyrase and topoisomerase IV have distinct essential roles in bacterial DNA replication. DNA gyrase, a type II DNA topoisomerase, was the first identified quinolone target; DNA gyrase is a tetramer composed of 2 GyrA and 2 GyrB subunits. DNA gyrase introduces negative superhelical twists in DNA, an activity important for initiation of DNA replication. DNA gyrase also facilitates DNA replication by removing positive super helical twists. Topoisomerase IV, another type II DNA topoisomerase, is composed of 2 ParC and 2 ParE subunits. DNA gyrase and topoisomerase IV are structurally related; ParC is homologous to GyrA and ParE is homologous to GyrB. Topoisomerase IV acts at the terminal states of DNA replication by allowing for separation of interlinked daughter chromosomes so that segregation into daughter cells can occur. Fluoroquinolones inhibit these topoisomerase enzymes by stabilizing either the DNA-DNA gyrase complex or the DNA-topoismerase IV complex; these stabilized complexes block movement of the DNA replication fork and thereby inhibit DNA replication resulting in cell death. ... Ciprofloxacin is cytotoxic to a variety of cultured mammalian cell lines at concn that deplete cells of mtDNA. The IC50 values for ciprofloxacin varied from 40-80 ug/ml depending on the cell line tested. Cytotoxicity required continuous exposure of cells to drug for 2-4 days, which corresponded to approx three or four cell doublings. Shorter times of drug exposure did not cause significant cytotoxicity. In addition, cells became drug resistant when they were grown under conditions that bypassed the need for mitochondrial respiration. Resistance was not due to a decr in cellular drug accumulation, ... /indicating/ that ciprofloxacin cytotoxicity is caused by the loss of mtDNA encoded functions. Analysis of mtDNA from ciprofloxacin treated cells revealed the presence of site specific, double stranded DNA breaks. ... Exonuclease protection studies indicated that the 5'-, but not the 3', ends of the drug induced DNA breaks were tightly assoc

Pharmacodynamics

Ciprofloxacin is a second generation fluoroquinolone that is active against many Gram negative and Gram positive bacteria. It produces its action through inhibition of bacterial DNA gyrase and topoisomerase IV. Ciprofloxacin binds to bacterial DNA gyrase with 100 times the affinity of mammalian DNA gyrase. There is no cross resistance between fluoroquinolones and other classes of antibiotics, so it may be of clinical value when other antibiotics are no longer effective. Ciprofloxain and its derivatives are also being investigated for its action against malaria, cancers, and AIDS.