Nitroxoline

Nitroxoline is an antibacterial and antifungal drug that belongs to the quinoline class. It is widely used for the treatment and prevention of urinary tract infections (UTIs) caused by susceptible microorganisms, as well as for the treatment of prostatitis, epididymitis, and infections affecting the kidneys and bladder. Nitroxoline is effective against a wide range of Gram-positive and Gram-negative bacteria, as well as some types of fungi, including Candida.

The mechanism of action of nitroxoline is the inhibition of DNA synthesis in microbial cells, which leads to their death. The drug disrupts the processes of biosynthesis in the cells of microorganisms at several levels, so it remains effective against a wide range of pathogens.

Nitroxoline is usually prescribed as oral tablets. The recommended dosage and duration of treatment may vary depending on the severity and type of infection, as well as the patient's age and condition. It is well tolerated by most patients, but like any medical drug, it can cause side effects such as gastrointestinal disturbances or allergic reactions.

It is important to consult your doctor before starting nitroxoline, especially if you have a chronic condition or are taking other medications, to avoid interactions and unwanted side effects.

Indications Nitroxoline

1. Cystitis: Inflammation of the bladder caused by infection. Nitroxoline can be used to treat acute and chronic forms of cystitis.
2. Urethritis: Inflammation of the urethra, most often caused by infection. Nitroxoline may be effective in treating urethritis of different nature.
3. Pyelonephritis: Inflammation of the renal calyx-lochanous system, usually caused by bacterial infection. Nitroxoline may be recommended for the treatment of pyelonephritis.
4. Prevention of recurrent urinary tract infections: In some patients with recurrent urinary tract infections, especially recurrent cystitis, nitroxoline may be used to prevent recurrent exacerbations.
5. Treatment of infections caused by microorganisms sensitive to it: Nitroxoline is widely used to treat infections caused by bacteria sensitive to its antibacterial action.

Release form

Nitroxoline tablets: The standard dosage is 50 mg or 100 mg of nitroxoline per tablet. The specific dosage and duration of treatment is determined by the doctor depending on the type and severity of the infection, as well as the individual characteristics of the patient.

Pharmacodynamics

1. Inhibition of DNA synthesis: Nitroxoline is a derivative of 8-hydroxyquinoline, which is able to inhibit DNA synthesis in microorganisms. This leads to impairment of their growth and reproduction.
2. Penetration into the cells of microorganisms: Nitroxoline is able to penetrate into the cells of microorganisms, where it exerts its antimicrobial action, preventing the normal functioning and reproduction of microbes.
3. Activity against bacteria: Nitroxoline is effective against a variety of bacteria, including Gram-positive and Gram-negative bacteria. It can be used in the treatment of urinary tract infections caused by bacterial flora.
4. Activity against fungi and protozoa: In addition, nitroxoline has activity against some fungi and protozoa, making it useful for treating infections caused by these pathogens.

Nitroxoline has activity against a variety of bacteria, including many types of Gram-positive and Gram-negative microorganisms, as well as some fungi and protozoa. Here are some of the bacteria that nitroxoline is active against:

1. Gram-positive bacteria:

   • Staphylococcus spp. (including Staphylococcus aureus)
   • Streptococcus spp.
   • Enterococcus spp.
   • Corynebacterium spp.
   • Listeria spp.

2. Gram-negative bacteria:

   • Escherichia coli
   • Klebsiella spp.
   • Proteus spp.
   • Enterobacter spp.
   • Citrobacter spp.
   • Serratia spp.
   • Salmonella spp.
   • Shigella spp.
   • Haemophilus influenzae
   • Neisseria gonorrhoeae
   • Neisseria meningitidis

3. Other microorganisms:

   • Mycobacterium tuberculosis
   • Trichomonas vaginalis
   • Candida spp.

This is not a complete list of all microorganisms against which nitroxoline is active, and the effectiveness of the drug may vary depending on the region and the resistance of local strains of bacteria.

Nitroxoline is an antibiotic that was originally used to treat urinary tract infections caused by microorganisms such as Escherichia coli. Its mechanism of action involves chelating (binding) Zn2+ and Fe2+ ions from the biofilm matrix, which inhibits bacterial growth and development. Nitroxolin has a broad spectrum of antibacterial activity, including activity against carbapenem-resistant strains, and can be used as a treatment option for uncomplicated urinary tract infections (Fuchs et al., 2022).

In addition, recent studies have shown the potential of nitroxoline as a treatment for cancer. In particular, it was found to induce apoptosis and inhibit prostate tumor growth in vitro and in vivo, acting through activation of AMPK (AMP-activated protein kinase), which leads to inhibition of the mTOR-p70S6K signaling pathway and causes cell cycle arrest (Chang et al., 2015).

Nitroxoline has also shown activity against Pseudomonas aeruginosa biofilms, inhibiting their formation and promoting their breakdown by chelating iron and zinc ions, making it a promising agent for controlling biofilm infections (Sobke et al., 2012).

These studies show that nitroxolin has not only antimicrobial but also potentially antitumor effects, making it an interesting target for further research in various fields of medicine.

Pharmacokinetics

1. Absorption: Nitroxoline is usually well absorbed from the gastrointestinal tract after oral administration. Its absorption occurs in the upper portions of the intestine.
2. Distribution: Nitroxoline is well distributed in body tissues, including kidneys, urinary tract and soft tissues. It can also penetrate the plasma and blood-brain barriers.
3. Metabolism: Nitroxoline undergoes minimal metabolism in the liver. Most of the drug is excreted from the body in unchanged form.
4. Excretion: The main route of excretion of nitroxoline from the body is renal excretion through filtration in the kidneys and active secretion in the proximal and distal tubules. Small amounts of the drug are also excreted through the bile.
5. Half-life: The half-life of nitroxoline is relatively short, lasting approximately 2-4 hours. This means that the drug is usually taken several times a day to maintain a sufficient concentration in the blood to fight the infection.
6. Mechanism of Action: Nitroxoline is an antibacterial drug and acts by inhibiting bacterial DNA synthesis. It is active against a wide range of bacteria, including some species of Gram-positive and Gram-negative bacteria, as well as some fungi and protozoa.

Dosing and administration

General recommendations for the use of nitroxoline for adults and children over 12 years of age:

Adults and children over 12 years of age

• The standard dosage for the treatment of unremitting urinary tract infections is usually 100 mg 4 times daily (every 6 hours).
• Theduration of treatment may vary from 7 to 10 days, depending on your doctor's advice and response to treatment. In some cases, the course of treatment may be extended to 2 to 3 weeks or longer for chronic infections.
• It is important to take nitroxoline regularly and complete the entire course of treatment, even if the symptoms have disappeared earlier, to completely destroy the infection and avoid recurrences.

Children under 12 years of age

• The dosage for children under 12 years of age is usually based on body weight and a lower dosage may be recommended for them. Always consult your pediatrician or specialist for the exact dosage for your child.

Special instructions

• Nitroxolin should be taken with meals or immediately after meals to improve absorption.
• During treatment with nitroxolin, you should drink enough fluids to ensure adequate hydration and to help flush the infection from the urinary tract.
• If you miss a dose, take it as soon as possible, but do not double the next dose if the time for the next dose is near.

Use Nitroxoline during pregnancy

At the moment, there are not enough studies to draw definitive conclusions about the safety of nitroxoline during pregnancy. Therefore, doctors usually try to avoid prescribing this drug to pregnant women, especially in the first trimester, when the baby's organs are forming.

However, if it is necessary to treat an infection, your doctor may decide to prescribe nitroxoline during pregnancy if the benefits of treatment outweigh the potential risks to the baby. If prescribing nitroxoline is necessary, the doctor will monitor its use and assess the possible risks.

Contraindications

1. Hypersensitivity: People with known hypersensitivity to nitroxoline or other quinolones should not use this drug because of the risk of allergic reactions.
2. Severe renal impairment: Use of nitroxoline may be contraindicated in patients with severe renal impairment due to the risk of accumulation of the drug in the body and its toxic effects.
3. Severe hepatic impairment: In patients with severe hepatic impairment, the use of nitroxoline may also be contraindicated due to the risk of toxic effects.
4. Pediatric age: The safety and efficacy of nitroxoline in children have not been established, therefore its use in this age group may be limited.
5. Pregnancy and breastfeeding: The use of nitroxoline during pregnancy and breastfeeding requires caution and may require consultation with a physician.
6. Hypersensitivityto quinolones: People with known hypersensitivity to quinolones, which include nitroxoline, should also avoid its use.
7. Epilepsy: The use of nitroxoline may be contraindicated in patients with epilepsy due to the risk of increased seizure activity.

Side effects Nitroxoline

1. Gastric Disorders: Nitroxolin can sometimes cause dyspeptic disorders such as nausea, vomiting, diarrhea, or abdominal pain.
2. Allergic Reactions: Allergic reactions such as skin rash, pruritus, urticaria or angioedema may occur in some patients.
3. Increased uric acid levels: Nitroxoline may increase the concentration of uric acid in the blood, which may worsen gout symptoms in some people.
4. Increase in bilirubin levels: Some patients may experience a temporary increase in blood bilirubin levels while taking nitroxoline.
5. Dysuria: Some patients may experience difficulty urinating or painful urination while taking nitroxoline.
6. Increase in liver enzymes: Some people may experience a temporary increase in the level of liver enzymes in the blood while taking nitroxoline.
7. Blood changes: Some patients may experience blood changes such as anemia or leukopenia.
8. Other side effects: Headache, dizziness, arthralgia or myalgia may occur.

Overdose

Information on nitroxoline overdose is limited, and there is no definitive data on what doses may be considered dangerous. However, if a suspected overdose occurs, immediate medical attention or consultation with a toxicologist should be sought.

Signs of overdose may include acute abdominal pain, nausea, vomiting, dizziness, fainting, seizures, tachycardia, and other symptoms.

Treatment of overdose includes symptomatic therapy and maintenance of vital functions. It is important to seek medical attention in a timely manner and do not attempt to treat the overdose on your own.

Interactions with other drugs

1. Drugs containing magnesium, aluminum, iron or zinc: Antacids containing magnesium, aluminum, iron or zinc may reduce the absorption of nitroxoline from the gastrointestinal tract. Therefore, it is recommended to take nitroxoline and antacids several hours apart.
2. Drugs that cause an alkaline urine reaction: Drugs that increase the pH of the urine (e.g., some carbonate or bicarbonate preparations) may decrease the effectiveness of nitroxoline.
3. Drugs thatdepress the CNS: Drugs that have central effects (e.g., some barbiturates, benzodiazepines, and narcotics) may increase side effects of nitroxoline, such as dizziness and drowsiness.
4. Drugs that increase hematologic side effects: Nitroxoline may increase hematologic side effects of drugs such as hypoglycemic agents, anticoagulants, and antihypertensives.
5. Drugs metabolized in the liver: Nitroxoline may affect the metabolism of other drugs metabolized in the liver, so it may be necessary to adjust their dosage.

Storage conditions

Nitroxoline should usually be stored at room temperature, which is between 15 and 25 degrees Celsius. The drug should be protected from direct sunlight, humidity and heat sources. It is recommended to store Nitroxoline out of the reach of children to avoid accidental use.

The drug should be stored in the original package or container in which it was provided by the manufacturer. It is important to avoid overfilling the drug or storing it in humid conditions to prevent decomposition or loss of efficacy.