What should a doctor do if his patient is allergic to antibiotics? Until recently, this question perplexed almost every therapist. Since the 60s of the last century, the answer to it has been found: quinolones. IN modern medicine drugs based on their derivatives - fluoroquinolones - are used. How they work and how they differ from antibiotics will be discussed in the article below.
This is a group of medications with a pronounced antimicrobial effect. Medicines in this category are used as antibiotics with a wide range of applications. However, these substances are not antibiotics in the full sense of the word. They have no natural analogue and differ from them in their structure.
A special feature of fluoroquinolones is the presence of a fluorine atom in the structure. This is where the name of the group came from. Second distinctive feature in the structures is the presence of a piperazine ring.
Fluoroquinolones are called second generation quinolones. Compared to their predecessors, fluoroquinolones have a high degree of activity.
Fluoroquinolones are classified by generation:
According to the list of fluoroquinolone drugs by generation, this substance belongs to the 4th generation. Release form: tablets and solution. Main substance: gatifloxacin. Indications for use: acute forms of otitis and sinusitis, gonorrhea, pneumonia, infections of joints, skin and bones, bronchitis, cystic fibrosis.
Contraindications: minor children, pregnancy, allergy to the drug.
Side effects: fever, sweating, tachycardia, gastrointestinal disorders, arrhythmia, hematuria, visual impairment.
Analogues: Gatispan, Tekvin, Tabris, Zarquin, Gatimak, Gatigem, Zikvin.
A pharmacological drug with this name is not officially registered. Gemifloxacin is the name of the active substance in many medicines. Indications for use: infectious diseases, exacerbation chronic bronchitis, sinusitis in the acute stage.
Contraindications: increased sensitivity to the substance, pregnancy and breastfeeding, increased QT interval on the electrocardiogram, age under 18 years.
Side effects: allergic reactions, disorder of the central nervous system(dizziness, tremors of the limbs, fear), changes in the functioning of the senses, renal failure.
Medicine containing gemifloxacin: tablets Faktiv.
This active substance It is produced as part of drugs under different trade names. Indications for use: pneumonia (including atypical), gonorrhea, exacerbation of bronchitis, cervicitis and urethritis.
Contraindications: epilepsy, conditions predisposing to impairment heart rate, pregnancy and lactation, allergies, age less than 18 years.
Side effects: allergies, dizziness, states of panic and fear, disturbances in the functioning of the organs of vision, hearing and taste, vomiting, loss of appetite, constipation.
Medicine containing grepafloxacin: Raksar.
An antibacterial drug from the fluoroquinolone group, belonging to the 3rd generation. Active ingredient: levofloxacin. Release form: tablets, eye drops, injection solution.
Indications for use: tablets are used to treat infectious diseases of the upper and lower respiratory tract, prostatitis, skin infections and urinary tract, bacteremia. Eye drops used to treat eye infections. The solution is used to treat infections of the upper and lower respiratory tract and ENT organs.
Contraindications: pregnancy and lactation, renal failure, age under 18 years, epilepsy.
Side effects: diarrhea, increased activity of liver enzymes, nausea.
Analogues:
A Russian drug based on the active substance is lomefloxacin. Release form: tablets. Indications: osteomyelitis, infections of the gastrointestinal tract, respiratory system, skin, urinary and biliary tract, as well as gonorrhea and chlamydia.
Contraindications: age under 18 years, pregnancy and lactation, allergy to the drug.
Side effects: cough, bronchospasm, gastrointestinal disorders, vasculitis, back and joint pain, disorders in the central nervous system, cardiovascular and genitourinary systems, allergic reactions.
Analogues: Abactal, Quintor, Pefloxacin, Maxaquin, Lofox, Lomacin, Xenaquin, Lomflox.
Active ingredient: moxifloxacin. Release form: tablets. Indications for use: urogenital infections, infections of the upper or lower respiratory tract, skin infections. In combination it is used to treat tuberculosis.
Contraindications: tendency to seizures, liver failure, allergies, pseudomembranous colitis, age under 18 years, pregnancy.
Side effects: anemia, gastrointestinal disorders, hyperglycemia, tachycardia, shortness of breath, hallucinations, convulsions.
Analogues: Avelox, Moxy Fluorine 400, Tevalox, Plevilox, Moximac, Moxin and Vigamox.
The active substance - nalidixic acid - is included in many drugs. Indications for use: cystitis, pyelitis, pyelonephritis, cholecystitis, inflammation of the middle ear.
Contraindications: depression of the respiratory center, impaired liver function, first trimester of pregnancy, age up to 2 years.
Side effects: vomiting, nausea, diarrhea, allergic reactions.
Nevigramon, Cystidix, Nilidixan, Nogram, Urodixin, Vintomilon, Negram. Release is carried out in tablets or capsules.
Release form: ophthalmic and ear drops, pills. Active substance: norfloxacin. Indications: used for infections of bacterial origin of the urinary tract, reproductive system, gastrointestinal tract, gonorrhea and “travelers' diarrhea”.
Contraindications: age under 18 years, pregnancy and lactation, intolerance to components.
Side effects: nausea, abdominal pain, diarrhea, vomiting, urethral bleeding, dizziness, headaches, tachycardia, tremor, arthralgia.
Analogues: Nolicin, Norilet, Normax, Sophasin, Chibroxin, Norbactin, Yutibid, Norfatsin, Noroxin, Renor.
Acid is included in the preparations antimicrobial action. Active substance: oxolinic acid. Indications for the use of fluoroquinolone: prostatitis, pyelonephritis, pyelitis, prevention of infection during instrumental studies(eg catheterization).
Contraindications: pregnancy, lactation, renal or liver failure, epilepsy, allergies, age under 2 years, old age.
Side effects: gastrointestinal disorders, allergic reactions, general weakness, dizziness, blurred vision, photosensitivity.
Preparations containing acid: Dioxacin and Gramurin (available in tablets).
One of the respiratory drugs is fluoroquinolones. Release form: ointment, tablets, solutions for infusion (drops). Active substance: ofloxacin. Indications for use: diseases of the ENT organs, urinary tract and kidney infections, pneumonia, chlamydia, prostatitis, gonorrhea, conjunctivitis, blepharitis and others.
Contraindications: pregnancy, lactation, age under 18 years, epilepsy, allergies.
Side effects: nausea, vomiting, flatulence, loss of appetite, diarrhea.
Analogues:
Domestic antimicrobial medicine. Active ingredient: pefloxacin. Release form: solution, tablets. Indications: typhoid fever, sepsis, prostatitis, gonorrhea, cholecystitis, eye infections, middle ear lesions, infectious lesions of the pharynx and larynx.
Contraindications: hemolytic anemia, epilepsy, pregnancy and breast-feeding, allergies, age under 18 years.
Side effects: headaches, fatigue, diarrhea, flatulence, dysuria, edema (allergic, including Quincke's edema), tachycardia and others.
Analogues: Leflocin, Perti, Pelox-400, Unikpef, Pefloxabol.
Release form: capsules, tablets, vaginal suppositories, suspension (for children). Active substance: pipemidic acid. Indications for use: urinary tract infections (diseases in acute or chronic form).
Contraindications: pregnancy, kidney failure.
Side effects: allergic skin reactions, nausea, photosensitivity, abdominal pain.
Analogues: Balurol, Naril, Pipefort, Pimidel, Pipem, Palin.
Active ingredient: Sparfloxacin is a poorly soluble substance of the fluoroquinolone group, which has an antibacterial effect. Release form: tablets. Indications: prostatitis, genital diseases, ENT infections, infections abdominal cavity, sepsis, skin infections, leprosy, gonorrhea.
Contraindications: epilepsy, tendency to change heart rhythm, pregnancy and lactation, renal failure, age under 18 years, allergies.
Side effects: headaches, tremors, convulsions, fear, shortness of breath, vomiting, fever, hyperglycemia, hot flashes, hepatitis and others.
Active substance: ciprofloxacin. Release form: drops (for eyes and ears), tablets. Indications for use: blepharitis, keratitis, barley, infections in the eye foreign bodies, conjunctivitis, otitis - for drops. Tablets are prescribed for diseases of the otolaryngological organs and respiratory tract infections, prostatitis, pyelonephritis, cystitis, peritonitis, sepsis.
Contraindications: viral keratitis, allergy. Eye drops should not be used by children under one year of age. For tablets: pregnancy and lactation, renal failure, epilepsy, age under 18 years.
Side effects: itching, slight burning, lacrimation, decreased vision or hearing, the appearance of white spots in patients with ulcerative eye lesions, allergic reactions. For tablets – gastrointestinal disorders, allergic reactions, dysfunction of the central nervous system.
Analogues: Tsifran, Tsipromed, Siflox, Floximed, Cipro, Tsiprinol, Microflox, Recipro, Tseprova, Quintor.
Fluoroquinolone group drugs are used in cases where conventional antibiotics will not cope:
Fluoroquinolones are widely used in gynecology, urology (for example, for prostatitis), ophthalmology, otolaryngology and other areas of medicine.
During clinical trials It was found that fluoroquinolones, unlike conventional antibiotics, do not weaken harmful bacteria and they kill them. This occurs by penetration of the active substance into the structure of the harmful microorganism and stopping the process of cell reproduction.
Fluoroquinolones penetrate the body faster. For several hours, the substances enter all tissues or fluids. After going through all the systems human body, drugs leave him through the urinary tract.
When taking drugs from this group, it is important to understand that they often cause side effects if taken incorrectly than antibiotics.
The frequency, dose and duration of the course are determined by the doctor. You should strictly follow his recommendations and maintain equal intervals between doses. If a dose is missed, take a single dose as quickly as possible. But you shouldn't do this when approaching next appointment. Doubling the dose is strictly prohibited. The tablets are taken with a sufficient amount of water.
It is worth adjusting the course of taking fluoroquinolones if other drugs are prescribed in combination. It's better to do this in case additional medications interact negatively with fluoroquinolones.
Medicines from the fluoroquinolone class are generally safe, but they have their own contraindications:
Negative effects occur less frequently than with antibiotics, but if taken incorrectly, they appear much more often:
Drugs of the quinolone group first began to be used in clinical practice in the early 60s. The mechanism of action is fundamentally different from other AMPs, due to which they are active against resistant (including multiresistant) strains of microorganisms. The class of quinols includes two main groups of drugs that have fundamental differences in pharmacokinetics, activity, structure, and breadth of indications for use: fluoroquinolones and non-fluorinated quinolones. At the core classification of fluoroquinolones It is time to introduce new drugs with improved antimicrobial properties into practice. The working classification of quinolones (proposed by R. Quintiliani in 1999) divides them into 4 generations:
I generation of fluoroquinolones:
- pipemidic (pipemidic) acid;
- oxolinic acid;
- nalidixic acid.
II generation of fluoroquinolones:
- ciprofloxacin;
- pefloxacin;
- ofloxacin;
- norfloxacin;
- lomefloxacin.
III generation of fluoroquinolones:
- sparfloxacin;
- levofloxacin.
IV generation of fluoroquinolones (respiratory):
- moxifloxacin.
These drugs have been registered in Russia. In other countries, other drugs of the quinolone class are used, mainly fluoroquinolones.
Gram-negative flora is predominantly affected by first generation quinolones, which do not create high concentrations in tissues and blood.
They have been approved for clinical use since the beginning of the 80s of the last century (II generation), are characterized by a wide range of antimicrobial activity (including staphylococci), have high bactericidal activity and good pharmacokinetics, due to which they are used in the treatment of infections various localizations. Fluoroquinolones, which were first used in the mid-90s (III and IV generations), have higher activity against gram-positive bacteria (primarily pneumococci), anaerobes (IV generation), intracellular pathogens, and also have even higher pharmacokinetics . Since a number of drugs are lek. forms for intravenous and oral administration are characterized by high bioavailability; stepwise therapy can be carried out, which will be clinically effective, but at the same time much cheaper than parenteral therapy.
Fluoroquinolones have high bactericidal activity, so for a number of drugs (norfloxacin, lomefloxacin, ofloxacin, ciprofloxacin) it became possible to develop dosage forms for topical use in the form of otic and eye drops.
Quinolones are bactericidal. The drugs inhibit two enzymes of the microbial cell that are important for life: topoisomerase IV and DNA gyrase. Under the influence of quinolones, DNA synthesis is disrupted.
Rice.
Activity spectrum
Basically, the effect of non-fluorinated quinolones extends to gram-negative microorganisms from the Enterobacteriaceae family (Salmonella spp., Shigella spp., Klebsiella spp., Proteus spp., Enterobacter spp., E.coli), to Neisseria spp. and Haemophillus spp. The clinical significance of pipemidic acid and oxolinic acid is not meaningful, even though their activity is directed against S. aureus and some strains of P. aeruginosa.
Fluoroquinolones have a more expanded spectrum of activity. Their activity extends to a number of gram-positive aerobic bacteria (Staphylococcus spp.), most strains of gram-negative bacteria, including E. coli and enterotoxigenic strains), Listeria spp., Brucella spp., Legionella spp., Pseudomonas spp., Pasteurella spp., Neisseria spp. ., Haemophilus spp., Vibrio spp., M.morganii, Citrobacter spp., Providencia spp., Serratia spp., Proteus spp., Klebsiella spp., Enterobacter spp., Salmonella spp., Shigella spp.
Also, fluoroquinolones (as a rule) are active against bacteria resistant to first generation quinolones. The high activity of fluoroquinolones of the III and, especially, IV generation is aimed at pneumococci (more active compared to drugs of the II generation), intracellular pathogens (Mycoplasma spp., M.tuberculosis, Chlamydia spp.), anaerobic bacteria (moxifloxacin), fast-growing atypical mycobacteria ( M.avium, etc.). At the same time, the effect on gram-negative bacteria is not weakened. These drugs have an important property: activity against a number of bacteria that exhibit resistance to second generation fluoroquinolones. This high activity against the causative agents of bacterial infections NDP and VDP has led to the name of such fluoroquinolones “respiratory”.
Fluoroquinolones in varying degrees show sensitivity to enterococci, U.urealyticum, H.pylori, Campylobacter spp., Corynebacterium spp.
Pharmacokinetics
All quinolones have good absorption in the gastrointestinal tract. When eating, absorption slows down, but the bioavailability of quinolones does not change significantly. Maximum blood concentrations are achieved on average 1-3 hours after oral administration. The drugs have the ability to penetrate the placenta and breast milk. Excretion occurs primarily through the kidneys, with high concentrations observed in urine. Partial excretion is carried out with bile.
First generation quinolones lack the ability to create therapeutic concentrations in the blood, tissues and organs. Oxolinic and nalidixic acids are intensively biotransformed and are predominantly excreted in the form of inactive and active metabolites. Metabolism of pipemidic acid is carried out in a small dose, the output is unchanged. Nalidixic acid has a half-life of 1 to 2.5 hours; pipemidic acid – from 3 to 4 hours; oxolinic acid - from 6 to 7 hours. After 3-4 hours (on average), maximum concentrations are created in the urine.
The elimination of quinolones is significantly slowed down in case of impaired renal function.
Fluoroquinolones, compared to non-fluorinated quinolones, are distinguished by a larger volume of distribution, the ability to create high concentrations in tissues and organs, and the ability to penetrate into cells. The exception is norfloxacin (the highest levels are observed in the prostate, bladder and intestines). Moxifloxacin, sparfloxacin, lomefloxacin, levofloxacin, ofloxacin are characterized by the highest tissue concentrations. Pefloxacin, levofloxacin, ofloxacin, and ciprofloxacin achieve therapeutic concentrations when passing through the BBB.
The physicochemical properties of the drug affect the degree of metabolism: biotransformation is most actively expressed in pefloxacin, with the least activity in levofloxacin, ofloxacin, and lomefloxacin. From 3-4 to 15-28% of the dose taken is excreted in feces.
Various fluoroquinolones have specific half-lives - from 3-4 hours (norfloxacin) to 12-14 hours (moxifloxacin, pefloxacin) and up to 18-20 hours (as with sparfloxacin).
Impaired renal function has the greatest effect on prolonging the half-life of lomefloxacin, levofloxacin and ofloxacin. In case of severe renal failure, the dosage regimen of all fluoroquinolones should be adjusted. In case of severe liver dysfunction, it may be necessary to adjust the dosage of pefloxacin.
During hemodialysis, fluoroquinols are removed in small quantities - ofloxacin is removed by 10-30%, other drugs - less than 10%.
Adverse reactions
For all quinolones general adverse reactions.
Allergic reactions: photosensitivity (most typical for sparfloxacin and lomefloxacin); angioedema, itching, rashes.
CNS: convulsions, tremor, paresthesia, blurred vision, dizziness, headache, insomnia, drowsiness, ototoxicity.
Gastrointestinal tract: diarrhea, vomiting, nausea, lack of appetite, pain in the epigastric region, heartburn.
for quinolones of the first generation
Liver: hepatitis, cholestatic jaundice.
Hematological reactions: hemolytic anemia (in case of glucose-6-phosphate dehydrogenase deficiency); leukopenia, thrombocytopenia.
Typical adverse reactions for fluoroquinolones (in rare and very rare cases)
Heart: prolongation of the QT interval on the electrocardiogram.
Kidneys: transient nephritis, crystalluria.
Musculoskeletal system: tendon rupture, tendovaginitis, tendinitis, myalgia, arthralgia, arthropathy.
Other: The most common are pseudomembranous colitis, vaginal candidiasis and/or candidiasis of the oral mucosa.
Indications
First generation quinolones
are used when:
- intestinal infections (shigellosis, bacterial enterocolitis (nalidixic acid));
- UTI infections ( acute cystitis, anti-relapse therapy for chronic forms of infections). In case acute pyelonephritis should not be used.
Used for:
- sepsis;
- gonorrhea;
- eye infections;
- infections of joints, bones, soft tissues and skin;
- prostatitis;
- UTI infections (pyelonephritis, cystitis);
- infections of the pelvic organs;
- intra-abdominal infections;
- anthrax;
- intestinal infections (cholera, yersiniosis, generalized salmonellosis, typhoid fever, shigellosis);
- NPD infections: legionellosis, nosocomial and community-acquired pneumonia, exacerbation of chronic bronchitis;
- infections of the upper respiratory tract: malignant otitis externa, sinusitis (especially provoked by multidrug-resistant strains);
- neutropenic fever;
- meningitis caused by gram-negative microflora (ciprofloxacin);
- bacterial infections in patients with cystic fibrosis;
- tuberculosis (lomefloxacin, ofloxacin, ciprofloxacin in combination therapy for drug-resistant tuberculosis).
The use of norfloxacin, taking into account the pharmacokinetics, is limited to treatment intestinal infections, prostatitis and UTI infections.
Contraindications
For all quinolones
- pregnancy period;
- deficiency of glucose-6-phosphate dehydrogenase;
- allergic manifestations after taking quinolone drugs.
Additional contraindications for quinolones of the first generation
:
- severe cerebral atherosclerosis;
- severe dysfunction of the kidneys and liver.
Additional contraindications for all drugs - fluoroquinolones:
- lactation period;
- childhood age.
Warnings
Allergy. Cross-allergic reactions to all quinolones occur.
Pregnancy. There is no reliable clinical data on the toxic effects of quinolones on the fetus. In isolated cases, hydrocephalus and increased intracranial pressure, bulging fontanel in newborns whose mothers were prescribed nalidixic acid during pregnancy. An experiment was conducted, as a result of which arthropathy developed in immature animals when using all quinolones - therefore, taking all quinolones during pregnancy is not recommended.
Lactation period. Quinolones are able to pass into breast milk in small quantities. There is evidence that hemolytic anemia was discovered in newborns whose mothers used nalidixic acid during lactation. The result of the experiment showed that quinolones cause arthropathy in immature animals - therefore, during the period when quinolones are prescribed to nursing mothers, the child should be transferred to artificial feeding.
Pediatrics. Experimental data have shown that it is not recommended to take quinolones during the formation of the osteoarticular system. Nalidixic acid should not be prescribed to children under 3 months, pipemidic acid – up to 1 year, and oxolinic acid – up to 2 years.
It is not recommended to prescribe fluoroquinolones to children and adolescents. The exception is the use of life-saving important indications– infections with neutropenia; severe infectious diseases of various localizations against the background of multidrug-resistant strains of bacteria; exacerbation of infection in cystic fibrosis (clinical experience, as well as special studies on the use of fluoroquinolones showed that the risks of damage to the osteoarticular system in children and adolescents are not justified).
Geriatrics. After taking fluoroquinolones, especially together with glucocorticoids, older people are at risk of tendon rupture.
Acute porphyria. Quinolones are not recommended for patients with acute porphyria, since animal experiments have shown that they are capable of creating a porphyrinogenic effect.
Central nervous system diseases. Patients with convulsive syndromes patients with a history of quinolones should not be prescribed, since they have a stimulating effect on the central nervous system. Patients with disorders cerebral circulation, parkinsonism and epilepsy are different increased risk development of seizures. Using nalidixic acid may cause increased pressure inside the skull.
Impaired liver and kidney function. In case of liver and kidney failure, the use of first generation quinolones is prohibited - as a result of the accumulation of drugs and their metabolites, the risk of toxic effects increases. In severe renal failure, fluoroquinolone doses should be adjusted.
Drug interactions fluoroquinolones
When taken together with antacids and other drugs that contain bismuth, iron, zinc, and magnesium ions, a decrease in the bioavailability of quinolones may be observed as a result of the formation of chelate complexes without the ability to be absorbed.
When taken with pipemidic acid, ciprofloxacin, norfloxacin and pefloxacin, the elimination of methylxanthines (caffeine, theophylline) may slow down and the risk of their toxic manifestations may increase.
Quinolones are antagonists of nitrofuran derivatives; a combination of these drugs is not recommended.
In the case of co-administration with NSAIDs, methylxanthine and nitroimidazole derivatives, the risk of developing the neurotoxic effects of quinolones increases.
The metabolism of indirect anticoagulants in the liver can be impaired by the effects of first generation quinolones, norfloxacin and ciprofloxacin, resulting in an increase in prothrombin time and the risk of bleeding. If simultaneous use is still necessary, the doses of anticoagulants should be adjusted (if necessary).
Concomitant use with glucocorticoids increases the risk of tendon rupture (especially in elderly patients).
Combined use with cimetidine and azlocillin leads to a decrease in tubular secretion, and, consequently, to a slowdown in the elimination of fluoroquinolones and an increase in their concentration in the blood.
The use of pofloxacin, norfloxacin and ciprofloxacin simultaneously with drugs that alkalinize the urine (sodium bicarbonate, citrates, carbonic anhydrase inhibitors) causes an increased risk of non-fluorotoxic effects and crystalluria.
Patient Information
Take quinolones orally with plenty of water at least 2 hours before or 6 hours after taking bismuth, zinc, iron and antacids.
It is prohibited to use expired medications.
Throughout the entire course of therapy, strictly adhere to the treatment regimen and regimen, take doses at regular intervals, and do not miss the next dose. If a dose was missed, then take it as soon as possible; if it is time to take the next dose soon, then do not take the missed dose. Do not double the dosage. Maintain the duration of treatment.
During therapy, drink a sufficient amount of fluid (1.2-1.5 liters per day).
While using the medications and for at least 3 days after the end of therapy, do not expose to direct sunlight or ultraviolet rays.
If there is no improvement within several days or new symptoms appear, consult your doctor. If pain occurs in the tendons, it is necessary to rest the affected joint and consult a doctor.
Drugs of the quinolone class, used in clinical practice since the early 60s, have a mechanism of action that is fundamentally different from other AMPs, which ensures their activity against resistant, including multiresistant, strains of microorganisms. The class of quinolones includes two main groups of drugs that differ fundamentally in structure, activity, pharmacokinetics and breadth of indications for use: non-fluorinated quinolones and fluoroquinolones. Quinolones are classified according to the time when new drugs with improved antimicrobial properties were introduced into practice. According to the working classification proposed by R. Quintiliani (1999), quinolones are divided into four generations:
Classification of quinolones
I generation:
Nalidixic acid
Oxolinic acid
Pipemidic (pipemidic) acid
II generation:
Lomefloxacin
Norfloxacin
Ofloxacin
Pefloxacin
Ciprofloxacin
III generation:
Levofloxacin
Sparfloxacin
IV generation:
Moxifloxacin
The listed drugs are registered in Russia. Some other drugs of the quinolone class are also used abroad, mainly fluoroquinolones.
First generation quinolones are predominantly active against gram-negative flora and do not create high concentrations in the blood and tissues.
Fluoroquinolones, approved for clinical use since the early 80s (II generation), are distinguished by a wide spectrum of antimicrobial action, including staphylococci, high bactericidal activity and good pharmacokinetics, which allows their use for the treatment of infections of various localizations. Fluoroquinolones, introduced into practice since the mid-90s (III-IV generation), are characterized by higher activity against gram-positive bacteria (primarily pneumococci), intracellular pathogens, anaerobes (IV generation), as well as even more optimized pharmacokinetics. The presence of dosage forms for intravenous administration and oral administration in a number of drugs, combined with high bioavailability, allows for stepwise therapy, which, with comparable clinical effectiveness, is significantly cheaper than parenteral therapy.
The high bactericidal activity of fluoroquinolones made it possible to develop them for a number of drugs (ciprofloxacin, ofloxacin, lomefloxacin, norfloxacin) dosage forms for topical use in the form of eye and ear drops.
Mechanism of action
Quinolones have bactericidal effect. By inhibiting two vital enzymes of the microbial cell - DNA gyrase and topoisomerase IV, they disrupt DNA synthesis.
Activity spectrum
Non-fluorinated quinolones act predominantly on gram-negative bacteria of the Enterobacteriaceae family (E. coli, Enterobacter spp., Proteus spp., Klebsiella spp., Shigella spp., Salmonella spp.), as well as Haemophillus spp. and Neisseria spp. Oxolinic and pipemidic acids are also active against S. aureus and some strains of P. aeruginosa, but this has no clinical significance.
Fluoroquinolones have a much wider spectrum. They are active against a number of gram-positive aerobic bacteria (Staphylococcus spp.), most gram-negative strains, including E. coli (including enterotoxigenic strains), Shigella spp., Salmonella spp., Enterobacter spp., Klebsiella spp., Proteus spp., Serratia spp., Providencia spp., Citrobacter spp., M.morganii, Vibrio spp., Haemophilus spp., Neisseria spp., Pasteurella spp., Pseudomonas spp., Legionella spp., Brucella spp., Listeria spp.
In addition, fluoroquinolones are usually active against bacteria resistant to first generation quinolones. Fluoroquinolones of the III and, especially, IV generation are highly active against pneumococci, more active than drugs of the II generation against intracellular pathogens (Chlamydia spp., Mycoplasma spp., M.tuberculosis, fast-growing atypical mycobacteria (M.avium, etc.), anaerobic bacteria (moxifloxacin). At the same time, the activity against gram-negative bacteria is not reduced. An important property of these drugs is their activity against a number of bacteria that are resistant to second-generation fluoroquinolones. Due to their high activity against the causative agents of bacterial infections, UDP and NDP, they are sometimes called “. respiratory fluoroquinolones.
Enterococci, Corynebacterium spp., Campylobacter spp., H.pylori, U.urealyticum are sensitive to fluoroquinolones to varying degrees.
Pharmacokinetics
All quinolones are well absorbed from the gastrointestinal tract. Food may slow the absorption of quinolones but does not significantly affect bioavailability. Maximum concentrations in the blood are achieved on average 1-3 hours after oral administration. The drugs cross the placental barrier and pass into breast milk in small quantities. They are excreted primarily by the kidneys and create high concentrations in the urine. Partially excreted in bile.
First generation quinolones do not create therapeutic concentrations in the blood, organs and tissues. Nalidixic and oxolinic acids undergo intensive biotransformation and are excreted mainly in the form of active and inactive metabolites. Pipemidic acid is little metabolized and is excreted unchanged. The half-life of nalidixic acid is 1-2.5 hours, pipemidic acid - 3-4 hours, oxolinic acid - 6-7 hours. Maximum concentrations in urine are created on average after 3-4 hours.
If renal function is impaired, the elimination of quinolones is significantly slowed down.
Fluoroquinolones, unlike non-fluorinated quinolones, have a large volume of distribution, create high concentrations in organs and tissues, and penetrate into cells. The exception is norfloxacin, the highest levels of which are observed in the intestines, urinary tract and prostate gland. The highest tissue concentrations are achieved by ofloxacin, levofloxacin, lomefloxacin, sparfloxacin, moxifloxacin. Ciprofloxacin, ofloxacin, levofloxacin and pefloxacin cross the BBB, reaching therapeutic concentrations.
The degree of metabolism depends on the physicochemical properties of the drug: pefloxacin is biotransformed most actively, lomefloxacin, ofloxacin, levofloxacin are least actively biotransformed. From 3-4% to 15-28% of the dose taken is excreted in feces.
The half-life of various fluoroquinolones ranges from 3-4 hours (norfloxacin) to 12-14 hours (pefloxacin, moxifloxacin) and even up to 18-20 hours (sparfloxacin).
In cases of renal dysfunction, the half-life of ofloxacin, levofloxacin and lomefloxacin is most significantly prolonged. In case of severe renal failure, dose adjustment of all fluoroquinolones is necessary. In case of severe liver dysfunction, a dose adjustment of pefloxacin may be required.
During hemodialysis, fluoroquinolones are removed in small quantities (ofloxacin - 10-30%, other drugs - less than 10%).
Adverse reactions
Common to all quinolones
Gastrointestinal tract: heartburn, epigastric pain, loss of appetite, nausea, vomiting, diarrhea.
CNS: ototoxicity, drowsiness, insomnia, headache, dizziness, visual disturbances, paresthesia, tremor, convulsions.
Allergic reactions: rash, itching, angioedema; photosensitivity (most typical for lomefloxacin and sparfloxacin).
Characteristic of 1st generation quinolones
Hematological reactions: thrombocytopenia, leukopenia; with deficiency of glucose-6-phosphate dehydrogenase - hemolytic anemia.
Liver: cholestatic jaundice, hepatitis.
Characteristic for fluoroquinolones (rare and very rare)
Musculoskeletal system: arthropathy, arthralgia, myalgia, tendonitis, tendovaginitis, tendon rupture.
Kidneys: crystalluria, transient nephritis.
Heart: prolongation of the QT interval on the electrocardiogram.
Others: most often - candidiasis of the oral mucosa and/or vaginal candidiasis, pseudomembranous colitis.
Indications
First generation quinolones
UTI infections: acute cystitis, anti-relapse therapy for chronic forms of infections. Should not be used for acute pyelonephritis.
Intestinal infections: shigellosis, bacterial enterocolitis (nalidixic acid).
Fluoroquinolones
URT infections: sinusitis, especially caused by multidrug-resistant strains, malignant otitis externa.
NPD infections: exacerbation of chronic bronchitis, community-acquired and nosocomial pneumonia, legionellosis.
Intestinal infections: shigellosis, typhoid fever, generalized salmonellosis, yersiniosis, cholera.
Anthrax.
Intra-abdominal infections.
Infections of the pelvic organs.
UTI infections (cystitis, pyelonephritis).
Prostatitis.
Gonorrhea.
Infections of the skin, soft tissues, bones and joints.
Eye infections.
Meningitis caused by gram-negative microflora (ciprofloxacin).
Bacterial infections in patients with cystic fibrosis.
Neutropenic fever.
Tuberculosis (ciprofloxacin, ofloxacin and lomefloxacin in combination therapy for drug-resistant tuberculosis).
Norfloxacin, taking into account the pharmacokinetics, is used only for intestinal infections, urinary tract infections and prostatitis.
Contraindications
For all quinolones
Allergic reaction to drugs of the quinolone group.
Glucose-6-phosphate dehydrogenase deficiency.
Pregnancy.
Additionally for 1st generation quinolones
Severe dysfunction of the liver and kidneys.
Severe cerebral atherosclerosis.
Additionally for all fluoroquinolones
Childhood.
Breastfeeding.
Warnings
Allergy. Cross to all drugs of the quinolone group.
Pregnancy. There are no reliable clinical data on the toxic effects of quinolones on the fetus. There are isolated reports of hydrocephalus, increased intracranial pressure and bulging fontanel in newborns whose mothers took nalidixic acid during pregnancy. Due to the experimental development of arthropathy in immature animals, the use of all quinolones during pregnancy is not recommended.
Breastfeeding. Quinolones pass into breast milk in small quantities. There are reports of hemolytic anemia in newborns whose mothers took nalidixic acid during breastfeeding. In experiments, quinolones caused arthropathy in immature animals, therefore, when prescribing them to nursing mothers, it is recommended to transfer the child to artificial feeding.
Pediatrics. Based on experimental data, the use of quinolones is not recommended during the formation of the osteoarticular system. Oxolinic acid is contraindicated in children under 2 years of age, pipemidic acid - up to 1 year, nalidixic acid - up to 3 months.
Fluoroquinolones are not recommended for use in children and adolescents. However, existing clinical experience and special studies of the use of fluoroquinolones in pediatrics have not confirmed the risk of damage to the osteoarticular system, and therefore it is permissible to prescribe fluoroquinolones to children for health reasons (exacerbation of infection in cystic fibrosis; severe infections of various localizations caused by multidrug-resistant strains of bacteria; infections in neutropenia ).
Geriatrics. In older people, the risk of tendon rupture increases when using fluoroquinolones, especially in combination with glucocorticoids.
Diseases of the central nervous system. Quinolones have a stimulating effect on the central nervous system, so they are not recommended for use in patients with a history of seizures. The risk of developing seizures increases in patients with cerebrovascular accidents, epilepsy and parkinsonism. When using nalidixic acid, intracranial pressure may increase.
Impaired kidney and liver function. First generation quinolones should not be used in cases of renal and liver failure, since the risk of toxic effects increases due to the accumulation of drugs and their metabolites. Doses of fluoroquinolones in severe renal failure are subject to adjustment.
Acute porphyria. Quinolones should not be used in patients with acute porphyria, since in animal experiments they have a porphyrinogenic effect.
Drug interactions
When used simultaneously with antacids and other drugs containing magnesium, zinc, iron, and bismuth ions, the bioavailability of quinolones may decrease due to the formation of non-absorbable chelate complexes.
Pipemidic acid, ciprofloxacin, norfloxacin and pefloxacin may slow down the elimination of methylxanthines (theophylline, caffeine) and increase the risk of their toxic effects.
The risk of neurotoxic effects of quinolones increases when combined with NSAIDs, nitroimidazole derivatives and methylxanthines.
Quinolones exhibit antagonism with nitrofuran derivatives, so combinations of these drugs should be avoided.
First generation quinolones, ciprofloxacin and norfloxacin can interfere with the metabolism of indirect anticoagulants in the liver, which leads to an increase in prothrombin time and the risk of bleeding. If used concomitantly, dose adjustment of the anticoagulant may be necessary.
Fluoroquinolones should be prescribed with caution concomitantly with drugs that prolong the QT interval, as the risk of developing cardiac arrhythmias increases.
When used simultaneously with glucocorticoids, the risk of tendon rupture increases, especially in the elderly.
When using ciprofloxacin, norfloxacin and pefloxacin together with drugs that alkalinize the urine (carbonic anhydrase inhibitors, citrates, sodium bicarbonate), the risk of crystalluria and nephrotoxic effects increases.
When used simultaneously with azlocillin and cimetidine, due to a decrease in tubular secretion, the elimination of fluoroquinolones slows down and their concentrations in the blood increase.
Patient Information
When taken orally, quinolone medications should be taken with a full glass of water. Take at least 2 hours before or 6 hours after taking antacids and preparations of iron, zinc, bismuth.
Strictly follow the regimen and treatment regimens throughout the course of therapy, do not miss a dose and take it at regular intervals. If you miss a dose, take it as soon as possible; do not take if it is almost time for the next dose; do not double the dose. Maintain the duration of therapy.
Do not use drugs that have expired.
During the treatment period, maintain sufficient water regime (1.2-1.5 l/day).
Avoid direct exposure to sunlight and ultraviolet rays while using the drugs and for at least 3 days after the end of treatment.
Consult your doctor if improvement does not occur within a few days or if new symptoms appear. If pain occurs in the tendons, you should rest the affected joint and consult a doctor.
Table. Drugs of the quinolone/fluoroquinolone group. Main characteristics and application features
