Pimidel - description of the drug, instructions for use, reviews

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Manufacturers: Krka (Slovenia)

Active ingredients

• Pipemidic acid

Disease class

• Cystitis
• Urethritis and urethral syndrome
• Urinary tract infection without established localization
• Inflammatory disease of the prostate, unspecified

Clinical and pharmacological group

• Not indicated. See instructions

Pharmacological action

• Antibacterial
• Bactericidal

Pharmacological group

• Quinolones/fluoroquinolones

Pharmacological properties of the drug Pimidel

Pipemidic acid is a synthetic urinary antiseptic that has a bactericidal effect. Acts on most gram-negative bacteria, such as E. coli, Klebsiella, Proteus , as well as some strains of Pseudomonas aeruginosa and some gram-positive microorganisms. Pipemidic acid is well absorbed from the gastrointestinal tract, bioavailability is 93%. Maximum plasma concentrations are achieved 1–2 hours after oral administration. 58–88% is excreted by the kidneys. The concentrations achieved in the urine are significantly higher than the minimum concentration that inhibits individual microorganisms that cause infectious diseases of the urinary tract. The half-life is 2.15–4.6 hours.

Side effects of the drug Pimidel

The most common side effects are gastrointestinal disorders (epigastric pain, heartburn, nausea, vomiting, flatulence, diarrhea, constipation), which are usually mild. Mild allergic reactions such as rash, angioedema, and eosinophilia are rarely observed. There have been reports of isolated cases of thrombocytopenia, erythematous and bullous changes on the skin and anaphylactic reactions. Central nervous system disorders (dizziness, imbalance) may occur in elderly patients.

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Special instructions for the use of the drug Pimidel

Patients should avoid exposure to sunlight while being treated with Pimidel. Pipemidic acid can be prescribed to patients with renal failure, but if the creatinine clearance is ≤0.16 ml/s (10 ml/min), the concentration of the active substance in the urine is insufficient for effective treatment. There is no need to reduce the dose for patients with mild or moderate renal impairment. However, it is necessary to reduce the dose in case of severe renal impairment (creatinine clearance ≤30 ml/min). In patients with porphyria, pipemidic acid may cause relapse. Treatment with Pimidel may change the intestinal flora, resulting in an increase in the number of Clostridium difficile and, accordingly, pseudomembranous colitis may develop. During treatment with Pimidel, it is recommended to consume a sufficient amount of fluid to maintain adequate diuresis. Pimidel should be taken after meals. Pimidel is contraindicated during pregnancy and breastfeeding. Impact on the ability to drive vehicles and use technical devices. Due to possible dizziness and loss of balance, caution should be exercised when driving or using technical devices.

Tactics for using uroseptics in general practice

To this day, uroseptics remain the main means of pathogenetic therapy for urinary tract infections. The most important way to increase the effectiveness of treatment is not only the creation and implementation of new uroantiseptics, but also improving the tactics of using existing agents. Drugs that are classified as uroseptics are summarized in Table. 1.

Table 1. Pharmacological drugs related to uroseptics

The problem of optimal choice of uroseptic in the treatment of a particular patient dictates the need to answer many questions. First of all, it is necessary to find out the localization of the urinary tract infection, determine the type of pathogen and its sensitivity to the selected uroseptic, the severity of the inflammatory process, and the functional state of the kidneys. In addition, it is necessary to have a clear understanding of the pharmacokinetics and pharmacodynamics of the drug.

Only after answering these questions does the choice of drug become truly optimal.

Speaking about the localization of infection, we must not forget that even the same patient may have different microflora in the kidney parenchyma and in the urinary tract.

As a rule, in the early stages of the disease, a monoinfection is detected; with a longer course of the process, in the case of inadequate antibacterial therapy, microbial associations appear, including up to two or three types of pathogens, often both gram-negative and gram-positive.

The most common pathogens are Escherichia coli and enterococci (i.e., obligate intestinal flora), as well as the hemolytic variant of Escherichia coli, Proteus, Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella. Moreover, associations of various types of pathogens with pyelonephritis occur in 20-45.5% of cases. In approximately 15% of cases of chronic pyelonephritis, it is not possible to identify the pathogen in the usual way, either in urine cultures or in cultures of renal tissue. Pathogens that have transformed into forms lacking cell walls (L-forms) and mycoplasmas require complex diagnostic media and techniques for their detection.

Identification of the pathogen allows you to select the most effective uroseptic. Currently, there are clear recommendations on the choice of uroseptic depending on the pathogen, and there is a lot of information on this issue in the literature. In situations where urine culture and flora sensitivity results cannot be expected, standardized antibacterial regimens may be used. For example, it is possible to use gentamicin, if necessary in combination with cephalosporins, or a combination of carbenicillin (pyopene) with nalidixic acid, colymycin with nalidixic acid.

Currently, in severe forms of urological infection - pyelonephritis, urosepsis, in case of resistance to other classes of antimicrobial substances, in the presence of multiresistant strains of bacteria - it is recommended to use fluoroquinolone antibiotics.

If it is necessary to carry out therapy with uroseptics for a long time, with changing drugs every 7-10 days, it is advisable to consistently use drugs that act on the bacterial wall and on the metabolism of the bacterial cell. Sequential use of penicillin and erythromycin, cephalosporins and chloramphenicol, cephalosporins and nitrofurans is recommended to prevent the survival of protoplast and L-form bacteria.

All of the listed groups of uroseptics penetrate well into the tissues of the genitourinary system and urine, where concentrations sufficient to obtain a therapeutic effect are created. At the same time, checking the excretory function of the kidneys is mandatory in each case. With pronounced sclerotic changes and damage to the glomerular apparatus of the kidneys, the success of treatment decreases, and when glomerular filtration decreases to 30 ml/min, there is no point in carrying out antibacterial therapy, since it is impossible to obtain a therapeutic therapeutic concentration of drugs in the renal parenchyma. In addition, the risk of developing toxic effects increases sharply. A decrease in the functional capacity of the kidneys forces us to pay special attention to the nephrotoxicity of the drugs used.

Fluoroquinolones, oxacillin, methicillin, carbenicillin from the penicillin group, macrolides, cephalosporins, and chloramphenicol have virtually no nephrotoxic effects.

Ampicillin, lincomycin, nitrofurans, nalidixic acid, and some long-acting sulfonamides have slight nephrotoxicity. In the presence of renal failure, tetracyclines become nephrotoxic. Aminoglycosides (gentamicin, streptomycin, torbamycin, kanamycin) are always highly nephrotoxic.

The nephrotoxic effects of the drugs are enhanced by severe dehydration and while taking diuretics.

One of the most important criteria for choosing a drug is urine pH. Aminoglycosides and macrolides exhibit maximum effectiveness in an alkaline environment at pH = 7.5–9.0; as urine pH decreases, their activity decreases. The effectiveness of cephalosporins, fluoroquinolones, glycoproteins, tetracyclines, and chloramphenicol does not depend on urine pH. In an acidic environment at pH ≤ 5.5, penicillins, derivatives of naphthyridine, nitrofuran, quinolone, 8-hydroxyquinolone, and metepamine are most effective. All these drugs significantly reduce their activity as the environment becomes alkalized.

In order to increase the alkalinity of urine, it is possible to prescribe a dairy-vegetable diet and sodium bicarbonate. To reduce the pH of urine (acidify it), increase the consumption of bread and flour products, meat and eggs. Ammonium chloride, ascorbic acid, methionine, hippuric acid (which is found, for example, in cranberry juice) are prescribed. Any substance that reduces urine pH below 5.5 inhibits the development of bacteria in the urine.

In the presence of microbial associations, it is possible to use a combination of two uroseptics.

Fluoroquinolones have good compatibility with most antimicrobial drugs and the absence of adverse reactions during combined antibacterial therapy.

β-lactams (penicillins, cephalosporins), aminoglycosides and polypeptides have a synergistic effect and can be combined in severe forms of infection. Moreover, all of the listed groups of antibiotics exhibit antagonism when interacting with tetracyclines, macrolides, and lincomycin.

Levomycetin, tetracyclines and macrolides show indifference when prescribed together. Nitrofurantoin weakens the effect of nalidixic acid. It is considered inappropriate to prescribe the following combinations: furagin with chloramphenicol, furagin with sulfonamides, chloramphenicol with sulfonamides, methenamine with sulfonamides.

Both the choice of drug combination and the required duration of course therapy and the route of drug administration depend on the location of the infection, the severity of the process, and the pathogen.

Doses of drugs for course therapy are given in table. 2. When carrying out treatment, it should be remembered that resistance of microorganisms develops to some drugs. This should be especially taken into account if intermittent therapy is necessary. Preference should be given to drugs to which resistance develops relatively slowly: these are fluoroquinolones, ampicillin, chloramphenicol, depot sulfonamides. Resistance to furagin develops especially slowly, so this drug is the most important when carrying out long-term intermittent treatment.

Resistance of microorganisms to nalidixic acid, oxolinic acid, tetracyclines, streptomycin, and cephalosporins develops quite quickly and often.

Given the above, you should always find out which drugs were used in previous therapy and evaluate the degree of their effectiveness.

It is also necessary to clarify the side effects that occurred during previous therapy and take into account the possibility of their occurrence during the treatment.

All of the above indicates that even with a mass of recommendatory literature with a large number of different treatment regimens, the approach to the treatment of urinary tract infections cannot be mechanical and requires an individual choice of treatment tactics for each specific patient.

Literature

1. Padeiskaya E. N. The importance of fluoroquinolones in the treatment of urinary tract infections // Breast Cancer. No. 10. P. 477-478.
2. Bertrand G., Katzung. Basic and clinical pharmacology. T. 2.
3. Barkhanova A. G., Zakharova G. Yu. Use of antibacterial drugs in chronic pyelonephritis. Tutorial. Moscow, 1977. P. 23.
4. Nephrology in 2 vols. edited by I. E. Tareeva.

Questions that a general practitioner should answer when choosing a uroseptic

• At what pH of the environment is the uroseptic effect optimally realized?
• What is the possibility of the combined use of uroseptics, their interactions, synergism or antagonism of action?
• What is the required duration of course therapy to obtain the best effect?
• How quickly does drug resistance develop?
• What is the most appropriate route of administration of the drug?
• What is the optimal dose needed to treat a particular patient?
• What is the nephrotoxicity of uroseptic?
• What are the possible side effects?