Therapy for despair during Covid. Doctors' mistakes can cost lives

In addition to the fact that the incidence of coronavirus is growing, doctors - as well as places in hospitals - are becoming less and less, test results are waiting for a long time, those doctors who remain in service make a number of mistakes when prescribing a treatment regimen.

An infectious disease doctor and researcher at PSPbSMU named after A.V. helped to understand the situation Academician I.P. Pavlova Oksana Stanevich together with the “Not in vain” foundation.

We will talk about what mistakes doctors make, what examinations, in addition to the COVID-19 test, show the presence of coronavirus, why you should not immediately take antibiotics, and what medications you should have at home.

Playing blind

Most outpatient doctors immediately prescribe medications without properly examining the patient. The worst thing is that the doctor, in the absence of information, cannot adequately formulate his own indications for hospitalization.

“It often happens that people come to the hospital, literally breaking all the laws, doing tests on their own in a commercial laboratory, deceiving their doctor, deceiving the laboratory, saying that he is not sick with Covid, and self-propelled - on foot, in personal transport, in a taxi - arrives to the hospital in serious or moderate condition.”

What additional examination is needed?

When infected with coronavirus, it is necessary to constantly monitor saturation indicators, which are measured with a pulse oximeter. This device looks like a clothespin that is attached to your finger. It shows how saturated the blood is with oxygen, i.e. saturation. It is measured as a percentage, and the norm for a healthy person without diseases of the lungs and cardiovascular system is 98−99%.

During coronavirus infection, saturation should be measured at least 4 times a day and for at least 30 seconds.

Photo: Vladimir Gerdo/TASS

Additional examination, which should be prescribed by the attending physician, may include a chest examination on a computed tomography (CT) scanner, a complete blood count, a blood test for c-reactive protein* and d-dimer*.

Based on these indicators, it is possible to timely determine the criteria for hospitalization, even if saturation indicators do not deviate greatly from the norm.

Example: a 49-year-old woman had a temperature above 38.5 for five days, a terrible cough, and shortness of breath. At the same time, saturation did not fall below 95%. She took tests, and the value for c-reactive protein was 126. The norm for this indicator is up to 5. Such a pronounced increase can be considered the start of a cytokine storm*, which is considered a complication of coronavirus infection. The woman called an ambulance, the doctor listened to her and did not hear anything in the lungs, which happens very often with covid pneumonia. The doctor told her that the blood tests meant nothing at all and left. She, breaking quarantine, came to the hospital through an acquaintance, where she underwent a CT scan, which showed that 65% of her lungs were affected. This corresponds to the third degree of lung damage out of four.

*Cytokine storm is an excessive immune response of the body to an infection that affects organs without the participation of a pathogen.

*C-reactive protein (CRP) is a highly sensitive indicator of inflammation and infection and responds to significant tissue damage.

*D-dimer - intensity and nature of thrombus formation processes.

A significant increase in c-reactive protein begins with a reading above 50.

In the photo: a patient undergoing examination on a computed tomography machine (Photo: Sergey Savostyanov/TASS)

In the Russian Federation, the prevalence of cardiovascular diseases (CVD) has reached epidemic proportions. Patients with cardiac disorders predominate in appointments not only with general practitioners, but also with doctors of other specialties. Which patients from this group does the gastroenterologist think about? Of course, we are talking about those of them who take antiplatelet drugs and nonsteroidal anti-inflammatory drugs. According to modern recommendations, in order to prevent cardiovascular complications, patients with coronary heart disease (CHD) are advised to use antiplatelet drugs (aspirin, clopidogrel, ticlopidine) [1]. Meanwhile, to relieve pain caused by concomitant diseases (arthritis, musculoskeletal pathology, etc.), patients often uncontrollably take a wide variety of nonsteroidal anti-inflammatory drugs (NSAIDs).

Given the widespread prescription of antiplatelet drugs for long-term use, questions of the safety of this therapy become very relevant. The use of antiplatelet drugs and NSAIDs is associated with damage to the upper gastrointestinal (GI) mucosa, including erosive and ulcerative lesions, gastrointestinal bleeding and perforation [2, 3].

In people who regularly take NSAIDs, ulcerative lesions of the gastrointestinal tract occur in 25% of cases, and the incidence of bleeding and perforation is 2-4% [4, 5].

The incidence of major gastrointestinal bleeding with aspirin is 1.8 to 3.7%, and with dual antiplatelet therapy (aspirin and clopidogrel) from 3.0 to 4.9%, depending on the dose of aspirin (75-325 mg ) [6]. The development of upper gastrointestinal bleeding with low-dose aspirin is 0.5% per year (relative risk (RR) compared with placebo is 2.07; 95% CI 2.61-2.66) [7]. The risk of developing gastrointestinal bleeding increases sevenfold with the combination of clopidogrel and aspirin (odds ratio (OR): 7.4; 95% CI 3.5-15) compared with aspirin monotherapy [8].

Assessing the risk of adverse gastrointestinal effects of NSAIDs and antiplatelet drugs

Risk factors for the negative effects of antiplatelet agents and NSAIDs on the gastrointestinal tract are formulated in the recommendations given in the American College of Gastroenterology for the prevention of complications of gastropathy induced by NSAIDs. Gradations have been identified according to the degree of risk of negative effects of NSAIDs on the gastrointestinal tract: high, moderate and low risk [9]. In addition, the presence of Helicobacter pyloric infection is an independent and additional risk factor that must be considered separately (see table).

Based on these recommendations, many cardiac patients, even without a history of ulcers, are at high risk for developing gastrointestinal complications when taking NSAIDs and antiplatelet drugs.

NSAIDs and aspirin are most often taken by patients over 60 years of age, who, due to their age, immediately find themselves in a high-risk group. The increased incidence of gastrointestinal bleeding and perforation in old age compared to younger individuals is explained by an age-related decrease in endogenous prostaglandin synthesis. In addition, it has been proven that in old age the protective mechanisms of the gastroduodenal mucosa are directly affected: blood flow, mucin synthesis and bicarbonate secretion decrease. Older age negatively affects the course of peptic ulcer disease [10].

Moreover, most elderly patients are forced to take aspirin, clopidogrel, double and sometimes triple antiplatelet therapy (aspirin, clopidogrel, warfarin) for a long time. Concurrent use of NSAIDs is not uncommon.

Proton pump inhibitors: feasibility of prophylactic use

Clinicians must evaluate the risk/benefit ratio and balance between the beneficial effects of antiplatelet therapy in preventing cardiovascular events and adherence to the ancient medical principle of “do no harm.”

It is obvious that it is necessary to prevent NSAID gastropathy and gastrointestinal bleeding during antiplatelet therapy. An effective way to reduce the high risk of gastrointestinal complications caused by antiplatelet drugs may be the additional prescription of proton pump inhibitors (PPIs). According to international recommendations, PPIs are the drugs of choice for the treatment and prevention of NSAID-induced gastropathy and gastrointestinal lesions during antiplatelet therapy.

The effectiveness of this approach has been demonstrated in the treatment of NSAIDs, with aspirin monotherapy and with dual antiplatelet therapy with aspirin and clopidogrel.

Thus, the risk of gastric and duodenal ulcers induced by NSAIDs is reduced with the use of PPIs (OR 0.37; 95% CI 0.27-0.51) [11].

In a study by A. Lanas et al. [12] in 2777 patients with upper GI bleeding and 5532 controls, PPI use was associated with a reduced risk of bleeding for both low-dose aspirin users (OR 0.32; 95% CI 0.22–0.51) and and for those taking clopidogrel (OR 0.19; 95% CI 0.07-0.49).

In patients with coronary artery disease receiving dual antiplatelet therapy with aspirin and clopidogrel, prophylactic PPI administration reduces the incidence of upper gastrointestinal bleeding. These results were obtained in a large placebo-controlled randomized trial, COGENT, involving 3761 patients requiring long-term dual antiplatelet therapy (who had undergone acute coronary syndrome or coronary stenting) [13].

The addition of omeprazole at a dose of 20 mg per day to the combination of aspirin and clopidogrel was accompanied by a significant reduction in the risk of gastrointestinal bleeding by 45%. In the group of patients receiving PPIs, both any gastrointestinal disorders (RR=0.34; 95% CI 0.18-0.63; p<0.001) and overt bleeding from the upper gastrointestinal tract (RR=0) were less common. .13; 95% CI 0.03-0.56; p=0.001) compared with the placebo group. The COGENT trial demonstrated that the effectiveness of antiplatelet treatment was not reduced by the addition of a PPI. There was no statistically significant increase in the risk of cardiovascular events with the addition of PPIs to antiplatelet therapy. A total of 4.9% of patients in the PPI group and 5.7% of those in the placebo group experienced cardiovascular events (OR=0.99; 95% CI 0.68-1.44; p= 0.96). However, the reported results should be taken critically, since this study was terminated early for financial reasons.

Proton pump inhibitors when taking antiplatelet drugs: to whom and when?

Risk factors and comorbidities should be assessed when selecting patients for adjunctive PPI therapy (see table).

Age, use of warfarin, steroids, NSAIDs, or H. pylori infection increase the risk of gastrointestinal bleeding during antiplatelet therapy.
For clinical use, an algorithm has been developed to reduce the risk of negative effects of antiplatelet drugs on the gastrointestinal tract by using PPIs (see figure)
[14].

Figure 1. Patient selection algorithm for PPI therapy with concomitant antiplatelet treatment [14].

How to avoid drug interactions

Currently, the medical world is actively discussing the interaction and safety of combining clopidogrel with PPIs (especially with omeprazole), since PPIs have the potential to reduce the amount of the active metabolite of clopidogrel and the severity of its antiplatelet effect. Certain genetic polymorphisms and a high probability of drug interactions in the cytochrome P-450 system with the addition of PPIs can lead to changes in the antiplatelet effectiveness of clopidogrel PPIs [15].

Clopidogrel is a prodrug that is transformed into an active metabolite by the cytochrome P-450 system in the liver. The active metabolite of clopidogrel selectively and irreversibly blocks the binding of ADP to platelet receptors of the P2Y12 type, which in turn blocks their activation through the IIb/IIIa complex. Activation of clopidogrel occurs in two stages. Initially, it undergoes oxidative biotransformation in the liver with the participation of the isoenzymes CYP2C19, CYP1A2 and CYP2B6, turning into 2-oxo-clopidogrel. The second stage is the hydrolysis of 2-oxo-clopidogrel into the active metabolite of clopidogrel using isoenzymes CYP3A, CYP2B6, CYP2C9, CYP2C19.

The metabolism of clopidogrel and 2-oxo-clopidogrel is largely dependent on the induction or inhibition of CYP2C19, which is due to the influence of various drugs, as well as individual genetic polymorphisms [16].

The metabolism of PPIs, as well as clopidogrel, occurs in the cytochrome P-450 system, predominantly with the participation of CYP2C19 and to a lesser extent - CYP3A4.

The use of PPIs may inhibit the conversion of clopidogrel to its active metabolite through its effect on CYP2C19, leading to a weakening of its antiplatelet activity. The risk of drug failure increases when drug concentrations are dependent on variable activity of a single metabolic pathway. Such a high pharmacokinetic risk was found with clopidogrel [17].

Another explanation for the effect of PPIs on the activity of clopidogrel may be a change in intragastric pH during PPI administration, which changes the absorption of clopidogrel. PPIs block the proton pump of gastric parietal cells, and restoration of intragastric pH is possible only with the cessation of the long-term therapeutic effect of PPIs, after 12-24 hours.

In addition, pharmacokinetic and antiplatelet testing of the active metabolite of clopidogrel showed that the concentration and antiplatelet effects of the drug differ depending on the genetic polymorphism of the CYP2C19 enzyme. The CYP2C19*1 allele results in fully functioning clopidogrel metabolism. The CYP2C19*2 and *3 alleles do not effectively metabolize clopidogrel. Patients with two reduced activity alleles (homozygotes) exhibit slow metabolization of clopidogrel. Certain genetic polymorphisms can lead to a 50% increase in cardiovascular risk and a threefold increase in the risk of stent thrombosis in patients receiving clopidogrel [18].

Clinical effectiveness of combined use of proton pump inhibitors and clopidogrel

In December 2010, a consensus was published by the American College of Cardiology and the American College of Gastroenterology regarding the combined use of thienopyridines (clopidogrel, prasugrel) and PPIs, which covered in detail the issues of changes in the effectiveness of clopidogrel while taking PPIs [19]. The clinical trial results presented in these guidelines range from a statistically insignificant effect of PPIs on increasing the risk of cardiovascular events to a significant association between PPI use and cardiovascular risk.

In a retrospective cohort study, M. O'Donoghue et al. in 13,608 patients treated with clopidogrel or prasugrel after stenting, there was no effect of PPIs on increasing mortality due to cardiovascular disease, myocardial infarction or stroke (RR for clopidogrel 0.94; 95% CI 0.80-1.11) [20]. No differences were demonstrated between PPI types, including omeprazole (n=1675), lansoprazole (n=441), ezomprazole (n=613) and pantoprazole (n=1844). PPIs did not increase the incidence of cardiovascular events even in patients who were “poor metabolizers” who had reduced function of the CYP2C19 allele. In the CREDO (Clopidogrel for Reduction of Events During Observation) study, PPI use was associated with an increased incidence of cardiovascular events in both patients with and without clopidogrel use [21].

Only one randomized clinical trial, the above-mentioned COGENT trial, examined the relationship between clopidogrel and PPIs. It has been proven that PPIs have no effect on increasing cardiovascular risk with a parallel statistically significant reduction in the risk of gastrointestinal complications.

Possibilities of pantoprazole in the prevention of gastrointestinal complications against the background of antiplatelet drugs

To date, the latest recommendations (ACCF/ACG/AHA 2010 Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines) do not indicate the priority use of a particular PPI during antiplatelet therapy. A retrospective study (W. Ray, 2010) involving 20,596 patients did not show a significant effect of any of the PPIs used (esomeprazole, lansoprazole, omeprazole, rabeprazole, pantoprazole) on an increase in the frequency of cardiovascular episodes [22].

The latest meta-analysis by S. Shukla and S. Guba does not allow us to conclude that PPIs reduce the activity of clopidogrel. But still, simultaneously with clopidogrel, the authors recommend prescribing not omeprazole, but pantoprazole or rabeprazole, since the latter do not affect the cytochrome 2C19 system.

Based on knowledge of the pharmacokinetic properties of PPIs and their effect on the cytochrome P-450 system, we can talk about the advantages of prescribing pantoprazole (Controloc, Nycomed) to patients with cardiovascular pathology receiving antiplatelet drugs.

Pantoprazole has a lower affinity for the hepatic cytochrome P-450 system, does not affect its activity and does not produce clinically significant reactions with many drugs, including antiplatelet agents and NSAIDs. This significantly expands the scope of its application, since pantoprazole is more suitable for use in conjunction with other medications, allowing us to assume with greater confidence that their effect will not change in the direction of strengthening, weakening or perversion. As a result, the effect of other drugs metabolized with the participation of enzyme systems of this cytochrome is not weakened, which is especially important in elderly patients with cardiac problems who are forced to take several drugs at the same time.

Pantoprazole undergoes little first-pass metabolism and has a constant bioavailability after the first dose. Pantoprazole is the only PPI that binds to the proton pump cysteine ​​at position 822. Cysteine ​​822 is thought to provide stability and long-lasting inhibition of the proton pump and acid production. Therefore, pantoprazole is characterized by a longer acid-lowering effect [23].

At a wider pH range, pantoprazole accumulates in parietal cells and interacts with the thiol group of the proton pump. Being a more stable compound, pantoprazole is less likely to react with thiol groups of proteins outside the parietal cell, which allows us to rely on its predicted pharmacokinetic properties [24].

If we talk about drug interactions between antiplatelet drugs and pantoprazole, then the latter has a low ability to enter into this drug-drug interaction. This is due to the lower affinity of pantoprazole compared to other PPIs for the CYP2C19 and CYP3A4 isoenzymes.

Unlike most products formed in phase I biotransformation of other PPIs, the initial metabolite of pantoprazole 4-hydroxypantoprazole, formed by the CYP system, very quickly leaves the cytochrome P-450 system, as a result of which the possibility of competition with various drugs at the level of CYP isoenzymes is eliminated. 4-hydroxypantoprazole is then biotransformed secondarily (phase II) through conjugation with sulfate in the cytosol. This conjugation reaction is often considered to be the reason for pantoprazole's lower ability to engage in drug-drug interactions.

If we talk about pantoprazole drugs, the leading drug is the original pantoprazole - Controloc (Nycomed). The molecule of the original pantoprazole has a unique double shell, which protects the active substance from the aggressive acidic environment of the stomach and allows it to be absorbed in the intestines. Controloc has such properties as irreversible and complete blockade of proton pumps, linear bioavailability (the same for each day of therapy), independence from food intake, and compatibility with other drugs, including antiplatelet drugs. Thus, Controloc (Nycomed) is a priority drug for additional use in cardiac patients with cardiac problems at risk of developing gastrointestinal complications who are forced to take antiplatelet drugs. This is due to minimal drug-drug interactions, the influence of pantoprazole on the cytochrome P-450 system and a long-lasting, sustained acid-lowering effect.

Conclusion

The need for long-term use of antiplatelet drugs is associated with an increased risk of developing gastrointestinal tract damage. Additional prophylactic use of PPIs significantly reduces the risk of gastrointestinal bleeding, but raises conflicting opinions regarding the weakening of antiplatelet effectiveness and the problem of drug interactions. Metabolism of both PPIs and antiplatelet agents by CYP isoenzymes of the hepatic cytochrome P-450 system, as well as individual genetic polymorphism, determine the effectiveness and safety of this combination. Among PPIs, the original drug pantoprazole (Controloc, Nycomed) has the least potential for drug-drug interactions and can serve as the drug of choice when prescribed to cardiac patients with a high risk of developing gastrointestinal complications who are forced to constantly receive antiplatelet therapy.

Useless antibiotics

One of the common mistakes is prescribing antibiotics. But antibiotics have no effect on the coronavirus itself.

Back in the spring, research was carried out “in a hurry” and a regimen was developed - a combination of azithromycin and hydroxychloroquine. In laboratory conditions, hydroxychloroquine showed a positive effect, and the antibiotic azithromycin was used as a “courier” of hydroxychloroquine inside the cell.

In practice, this combination did not work. It did not improve the outcome of the disease, and people died just as often as those who did not receive these drugs. Moreover, this combination does not shorten the length of hospitalization and does not shorten the stay of the virus in the body.

Disservice

Azithromycin itself did not initially work and was simply a conduit for hydroxychloroquine. Even without reference to the coronavirus, Russian people are accustomed to treating any infection with antibiotics. And, what is absurd, outpatient doctors continue to use the azithromycin monotherapy regimen in the treatment of coronavirus infection.

Pneumonia caused by different causes (viruses or bacteria) affects the lung tissue in different ways, and for this reason, treatment tactics will differ.

There are 4 lines of antibacterial drugs on the World Health Organization (WHO) list that should be used in certain situations. The notorious azithromycin is included in the second line and is used for specific indications.

In addition, there is a list of antibiotics that are not recommended for use in certain combinations, because they have very pronounced side effects.

Now the most common combination of coronavirus treatment at the prehospital stage is a combination of azithromycin and levofloxacin. This particular combination is not recommended by WHO. It is prohibited by clinical pharmacologists, including in Russia.

Photo: Anton Vergun/TASS

Hormonal treatment for endometriosis.

Hormones for endometriosis are an almost obligatory part of treatment. This is physiologically justified, because the disease is hormone-dependent. Its main reason is the excessive production of estrogen in a woman’s body.

The doctor prescribes hormonal treatment for endometriosis to solve the following problems:

• normalization of the secretory activity of the ovaries and pituitary gland;
• prevention of further proliferation of endometrioid tissue.

Artificial suppression of menstruation is the essence of hormone therapy. Under the influence of active substances, physiological rejection of the uterine mucosa does not occur. Foci of its growth outside the uterus do not bleed, and the body recovers.

Other treatments include:

• Simulating menopause. The doctor prescribes hormonal drugs that reduce the level of sex hormones to minimum values.
• Suppression of ovulation. For this purpose, medications that contain synthetic androgens (male sex hormones) are used. These substances block the release of a mature egg from the follicle.

Drug treatment of endometriosis includes several groups of hormonal drugs. The doctor selects a treatment regimen individually, taking into account a number of factors:

• individual characteristics of a woman’s body;
• the patient’s desire to have children in the future;
• presence of contraindications.

It is difficult to cure endometriosis without hormones. Alternative treatment can only be considered as an additional treatment. Its effectiveness is difficult to predict. Further development of the disease and relapse cannot be ruled out.

Hormonal oral contraceptives for endometriosis.

Before determining a treatment regimen, the attending physician prescribes tests to determine which hormones are elevated. Each group of drugs for the treatment of a disease has a different pharmacological effect, so self-medication is unacceptable. The decision on conservative treatment or surgery is made only by a qualified specialist.

Advantages and disadvantages of hormonal treatment for endometriosis

The effectiveness of drugs for endometriosis depends on the stage of development of the disease. The highest therapeutic effect is observed at the initial stages of development of the pathological process. Early detection of pathology helps to avoid surgical intervention. The advantages of this treatment are:

• pain relief;
• stopping bleeding;
• restoration of reproductive function.

Along with the therapeutic effect, hormonal pills for endometriosis have a contraceptive effect. They are prescribed to women in the later stages of the disease as preoperative preparation and during the rehabilitation period. After a course of therapy, the woman’s body quickly recovers: the menstrual cycle normalizes and fertility is preserved.

Hormone treatment, like any other, has disadvantages:

• lack of therapeutic effect if the cause of endometriosis is not associated with an increased level of estrogen in the woman’s blood;
• duration of therapy (from 6 to 12 months);
• drug dependence may develop;
• Do not skip taking medications, otherwise breakthrough bleeding will occur;
• after discontinuation of drugs there is a risk of relapse.

With long-term use of hormones, a woman develops adverse reactions. The most common ones include:

• nausea;
• headache;
• violation of metabolic processes;
• depression;
• dysfunction of the circulatory and digestive systems.

Contraindications to hormone treatment

Not all patients are prescribed hormonal therapy. This method of conservative treatment of endometriosis has contraindications:

• endocrine disorders;
• renal and hepatic dysfunction;
• pathologies of the heart, blood vessels, hematopoiesis;
• diabetes;
• stomach ulcer, gastritis;
• tendency to allergies;
• hypersensitivity to individual components of drugs.

It is not advisable for women who are obese or smokers to take hormones. Contraindications include pregnancy, lactation, and the presence of cancer.

Treatment of endometriosis with hormonal drugs is the most effective way. There are various groups of medications that are prescribed to combat the disease. The drug therapy regimen is selected only by the doctor.

Based on materials from https://gormonal.ru

Spectacular side effect

The regimen of hydroxychloroquine and azithromycin that was initially recommended has significant side effects. Hydroxychloroquine damages the heart tissue, which can lead to heart rhythm disturbances, including paroxysmal atrial fibrillation. A rhythm disturbance can cause cardiac arrest or provoke the formation of blood clots.

The fact that hydroxychloroquine not only does not work, but is also harmful, became clear back in the summer. However, outpatient and sometimes inpatient doctors continue to prescribe it.

Moreover, it is included in clinical recommendations and, for example, in St. Petersburg is given free of charge to people who are being treated for Covid at home.

The azithromycin and levofloxacin regimen is also toxic to the heart and also disrupts the heart rhythm.

***

When taking antibiotics as an outpatient, antibiotic-associated diarrhea often occurs. This may hide a more serious complication - pseudomembranous colitis. Simply put, it is an inflammation of the large intestine where plaque-like, membrane-like formations appear on its walls. This manifests itself as an increase in bowel movements up to 5-10 times a day, but can reach up to 20 times.

When bacteria multiply, many toxins are released into the blood, which can lead to fever, intoxication, dehydration and septic condition. In extreme cases of dehydration, the kidneys, heart and brain begin to suffer.

The intestines may not work until intestinal paresis occurs. This condition can only be treated with surgery and is potentially life-threatening.

“We have had several cases where we have proven the occurrence of colitis due to pre-hospital antibiotic use. There is an analysis that allows us to determine that this is pseudomembranous colitis. This is a stool test for toxins A and B. Even if one toxin is detected, it is already colitis.”

Unfortunately, coronavirus infection simply does not have an application point for the use of antibiotics. It is impossible to cure Covid with antibiotics.

“A fatal complication of coronavirus infection—acute respiratory distress syndrome, when suddenly all the lungs shut down, the affected area expands, respiratory failure develops, and the person dies—antibiotics do not help.”

Curantil 25 mg No. 120 tablets

Instructions for medical use of the drug Curantil® N25 Trade name Curantil® N25 International nonproprietary name Dipyridamole Dosage form Film-coated tablets 25 mg Composition One tablet contains the active substance - dipyridamole 25 mg, excipients: core composition: corn starch, lactose monohydrate, sodium starch glycolate (type A), gelatin, colloidal anhydrous silicon dioxide, magnesium stearate; shell composition: hypromellose, talc, macrogol 6000, titanium dioxide (E 171), quinoline yellow (E 104), simethicone emulsion Description Yellow round flat-cylindrical tablets, film-coated, having almost plane-parallel surfaces Pharmacotherapeutic group Anticoagulants. Platelet aggregation inhibitors, excluding heparin. Dipyridamole. ATC code B01AC07 Pharmacological properties Pharmacokinetics After oral administration, dipyridamole is rapidly absorbed in the gastrointestinal tract (mostly in the stomach and partially in the small intestine). After oral administration, the maximum plasma concentration of dipyridamole is achieved after 1 hour. Dipyridamole is almost completely bound to plasma proteins. It accumulates in the heart and red blood cells, and is metabolized in the liver by binding to glucuronic acid. The half-life is 20–30 minutes. Dipyridamole is excreted in bile as a monoglucuronide. Pharmacodynamics Curantil® N 25 has an inhibitory effect on platelet aggregation and improves microcirculation. The drug has a mild vasodilator effect. The mechanism by which dipyridamole exerts its inhibitory effect on platelet aggregation may be due to inhibition of adenosine uptake (which is an inhibitor of platelet reactivity), inhibition of platelet phosphodiesterase, or stimulation of prostacyclin (PGI2) release. Dipyridamole inhibits the uptake of adenosine by endothelial cells, red blood cells and platelets. Thus, after the use of dipyridamole, an increased concentration of adenosine in the blood was observed, and platelet aggregation and thrombus formation provided by it decreased. In addition, the vasodilating effect of adenosine was enhanced. The enzyme phosphodiesterase breaks down the aggregation-inhibiting cyclic adenosine monophosphate (c-AMP) in platelets. Dipyridamole inhibits platelet phosphodiesterase, leading to the accumulation of c-AMP in them. Indications for use - treatment and prevention of ischemic cerebral circulatory disorders - prevention of arterial and venous thrombosis, as well as their complications - prevention of thromboembolism after heart valve replacement surgery. Method of administration and dosage Unless otherwise prescribed, the following dosage instructions apply: To reduce platelet aggregation, it is recommended to take 75–225 mg of dipyridamole/day (3-9 film-coated tablets of Curantyl® N 25), distributed over several doses. In severe cases, the dose may be increased to 600 mg dipyridamole/day. For the treatment and prevention of cerebrovascular accidents, it is recommended to take 3 tablets of Curantyl® N 25 3-6 times a day (225–450 mg dipyridamole). The maximum dose of dipyridamole should not exceed 450 mg/day (corresponds to 18 film-coated tablets of Curantyl® N 25). Therapy should begin with gradually increasing doses, and film-coated tablets should be taken on an empty stomach, without biting or breaking them, and with liquid. The duration of treatment and dose should be determined depending on individual need and tolerability. Curantil® N 25 is suitable for long-term treatment. Side effects Side effects that occur during the use of Curantil® N 25 in therapeutic doses are usually weak and transient. Sometimes - vomiting, diarrhea, nausea - dizziness, headache (including headache of vascular origin) and muscle pain (usually these side effects disappear with longer use of Curantyl® N 25) Rarely - hypersensitivity reactions such as rapidly transient skin rash and urticaria Isolated cases - increased tendency to bleeding during or after surgery - exacerbation of coronary heart disease - angina pectoris - myocardial infarction Frequency unknown - pain in the epigastrium - palpitations, tachycardia, bradycardia, flushing of the face, coronary steal syndrome (when using doses of more than 225 mg/day). - thrombocytopenia, changes in the functional properties of platelets, increased tendency to bleeding - weakness, a feeling of ear congestion, noise in the head, arthritis, rhinitis - as a result of a possible vasodilator effect, Curantil®N 25 in high doses can cause hypotension, a feeling of heat and tachycardia, especially in patients taking other vascular drugs - it has been shown that dipyridamole may be a component of gallstones. Contraindications - recent myocardial infarction - unstable angina - widespread stenosing atherosclerosis of the coronary arteries - subaortic stenosis - decompensated heart failure - arterial hypotension, collapse - severe heart rhythm disturbances - hemorrhagic diathesis - diseases with a tendency to bleeding (peptic ulcer of the stomach and duodenum etc.) - hypersensitivity to any of the components of the drug - childhood and adolescence under 18 years of age - lactation period Drug interactions Xanthine derivatives (found, for example, in coffee and tea) can weaken the vasodilatory effect of Curantil® N 25. It must be taken into account that with the simultaneous use of Curantil® N 25 and anticoagulants or acetylsalicylic acid or clopidogrel, the antithrombotic properties of the latter are enhanced. If Curantil® N 25 is used simultaneously with acetylsalicylic acid or anticoagulants, then it is necessary to take into account information about the risk and incompatibility of these drugs. Dipyridamole may enhance the effect of antihypertensive drugs. Dipyridamole may reduce the cholinergic properties of cholinesterase inhibitors. The use of antacids may reduce the effectiveness of Curantil® N 25. B-lactam antibiotics, tetracycline and chloramphenicol enhance the effect of dipyridamole. Dipyridamole increases the concentration of adenosine in the blood plasma and enhances its vasodilatory effect. If there is an urgent need for combined use with dipyridamole, the dosage of adenosine must be adjusted. Dipyridamole may also inhibit the absorption of fludarabine and reduce its effectiveness. Dipyridamole may cause a slight increase in the absorption of digoxin. Special instructions Pregnancy The safety of using Curantil® N 25 during pregnancy has not been established; therefore, the drug should not be used during pregnancy, especially in the first trimester, unless the expected benefit to the patient is greater than the possible risk to the fetus Curantil® N25 contains lactose, therefore Not recommended for patients with rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome. Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous machinery Even with proper use, Curantil® N 25 can indirectly affect the ability to drive vehicles and operate machines, since a change in reaction may occur as a result of a drop in blood pressure. Overdose Symptoms: general vasodilation, accompanied by hypotension, complaints characteristic of angina pectoris, tachycardia, feeling of heat, redness of the face, weakness and dizziness, anxiety. Treatment: symptomatic therapy for oral intoxication: - removal of the toxin (gastric lavage, inducing vomiting) - measures to reduce absorption. The dilating effect of Curantil® N 25 can be stopped by slow intravenous administration of aminophylline (50-100 mg over 60 seconds). If after this the complaints associated with angina pectoris persist, then sublingual nitroglycerin can be used. Release form and packaging 120 tablets are placed in 30 ml clear glass bottles with polyethylene stoppers. 1 bottle, along with instructions for medical use in the state and Russian languages, is placed in a cardboard pack. Storage conditions Store at a temperature not exceeding 25 °C. Keep out of the reach of children! Shelf life 3 years Do not use after expiration date. Conditions for dispensing from pharmacies By prescription Manufacturer Berlin-Chemie AG (Menarini Group) Glinker Weg 125 D-12489 Berlin, Germany Registration certificate holder Berlin-Chemie AG (Menarini Group), Germany Packaging organization Menarini - Von Heyden GmbH, Germany Address of the organization, receiving on the territory of the Republic of Kazakhstan, claims from consumers regarding the quality of products (products): Representative office of JSC Berlin-Chemie AG in the Republic of Kazakhstan Tel.: +7 727 2446183, 2446184, 2446185 Fax: +7 727 2446180 Email address

The deficit we create ourselves

Since spring, people in panic began to buy everything they thought they needed. At first it was buckwheat and toilet paper, then lemons, garlic and ginger, then medical masks, and gradually the turn came to basic mercury thermometers and medicines.

Those who have encountered coronavirus infection more closely may know about the drug dexamethasone, its analogue is prednisolone. Now it is almost impossible to find dexamethasone in pharmacies. There have been rumors that it can supposedly cure cytokine storm, is effective in preventing coronavirus, or can stop the more complex, fatal course of covid.

In the photo: oxygen concentrator (Photo: Sergey Malgavko/TASS)

“Back in the summer, a study was conducted in the UK, which showed that the administration of dexamethasone actually improved the outcome of the disease and made it possible not to develop more severe respiratory failure. However, there was one “but”, which for some reason is again not taken into account anywhere. The benefit of dexamethasone has been shown only in combination with oxygen support (prescribed when saturation decreases below 95%). In the absence of oxygen support, outcomes did not improve and there was even a trend towards worse outcomes.”

In outpatient treatment, dexamethasone cannot help. And if you decide to buy it “just in case,” then do not forget to buy an oxygen concentrator, the cost of which varies around 60-70 thousand rubles.

Release forms

Pharmaceutical companies involved in the production of the drug "Curantil" produce the drug only in tablet form. The product has an external difference from most drugs. The tablets are small in size and come in a round shape with a yellow color. Sales packaging - a transparent glass bottle or blisters.

The dosage of the drug can be of two types: 25 or 75 mg, the number of tablets per package is 10 pieces (blisters) or 100/120 pieces (bottles).

Each package is accompanied by instructions for use describing general information about the drug. It is recommended that you read the instructions before starting your appointment, even if the specialist has given all the necessary instructions.

Time for antibiotics: when needed

In the early stages - up to the 8th-9th day - there can be no talk of antibiotics at all. During this period, coronavirus pneumonia develops, which cannot be stopped by prescribing antibiotics.

Some may develop secondary bacterial pneumonia. This occurs more often in people with an initially suppressed immune status. For example, with decompensated diabetes mellitus.

“When there is a lot of glucose in the blood, bacterial microflora has a greater chance of superimposing viral pneumonia and stimulating the proliferation of bacteria in the lungs. It has certain laboratory signs. We cannot prescribe antibiotics for diabetes and Covid for prevention. Because it won’t work for prevention, antibiotics don’t prevent secondary bacterial pneumonia, they only treat it.”

To prevent the development of bacterial pneumonia, it is necessary to reduce glucose levels with the help of glucose-lowering drugs or insulin under the supervision of a doctor.

Photo: Vladimir Gerdo/TASS

When is it prescribed?

The prescription drug "Curantil" is prescribed after the diagnosis is determined for preventive and therapeutic purposes. The main effect of dipyridamole determines the indications for use.

Curantil is recommended for high blood pressure to reduce the risk of:

• myocardial infarction (not in acute form);
• thromboembolism;
• myocardial hypertension;
• insufficient blood circulation to the brain.

The drug "Curantil" lowers blood pressure, improves blood flow into small vessels, thins the blood, and reduces the risk of thrombocytopenia

The medicine can be used in combination with other medications, the action of which is aimed at normalizing blood circulation during the period of respiratory or inflammatory processes in the body.

The drug is also recommended during the post-infarction period of rehabilitation and during rehabilitation after installation of heart valves. "Curantil" can be prescribed by a gynecologist if there is a risk of placental insufficiency in women carrying a child.

Signs of secondary bacterial pneumonia

With secondary bacterial pneumonia, a clinical blood test will show an increase in the level of leukocytes, neutrophils, including their immature forms.

The patient may develop purulent sputum, colored - green, rusty, streaked with blood. Sputum may become more abundant.

Another sign of the development of secondary bacterial pneumonia is an increase in body temperature to 38.5 degrees or higher in the later stages - 12-14 days of Covid disease.

After 2 weeks of coronavirus infection in the body and the development of covid pneumonia, changes occur in the lung tissues that are most convenient for the addition of bacteria and the development of bacterial pneumonia.

“Changes in the lungs after covid pneumonia persist for about 8 weeks after recovery. This does not mean that post-Covid pneumonia needs to be treated somehow. Saturation should be restored to your normal by the end of the infection.”

Emergency care for acute pyelonephritis and hematuria

Acute pyelonephritis is a nonspecific infectious inflammation of the pyelocaliceal system and renal parenchyma. ARF is caused by Escherichia coli, Klebsiella, Proteus, Pseudomonas.

Routes of entry of an infectious agent into the kidney:

• ascending - foci of chronic inflammation are located in the female genital organs, lower urinary tract and less commonly in the colon;
• hematogenous - the source is an acute or subacute inflammatory process outside the urinary tract (mastitis, boil or carbuncle, etc.).

Predisposing factors for the development of acute pyelonephritis are hemodynamic or urodynamic disorders in the kidney or upper urinary tract. Acute pyelonephritis is more often observed in women.

The infection, once in the kidney, receives favorable conditions for its development in zones of hypoxia, where the inflammatory process occurs. An infected thrombus or embolus in the terminal vessels of the renal cortex causes an infarction followed by suppuration. The occurrence of multiple small suppurating infarctions in the cortex is classified as apostematous nephritis. The development of an extensive infarction with subsequent suppuration leads to the formation of a renal carbuncle.

With regard to the pathogenesis of the disease, primary and secondary pyelonephritis are distinguished (Fig. 1). Secondary pyelonephritis is based on organic or functional changes in the kidneys and urinary tract.

Depending on the passage of urine through the upper urinary tract, i.e. from the kidney to the pelvis and further along the ureter, acute pyelonephritis is distinguished between non-obstructive (if it is preserved) and obstructive (if it is disturbed).

Manifestations of acute pyelonephritis:

• chills;
• high fever (38–39°C and above);
• pain in the lower back (side);
• often nausea and vomiting;
• general intoxication.

Often acute pyelonephritis is preceded by frequent, painful urination at the end (clinical picture of acute cystitis).

Non-obstructive acute pyelonephritis can begin with dysuria and on the same day or 1-2 days later lead to high body temperature, chills and pain in the affected kidney. Chills may be replaced by heavy sweat with a short-term decrease in body temperature; pain in the lumbar region in some cases appears during urination and precedes chills and fever (vesicoureteral reflux!), and after them does not recur (rupture of the fornix of one or more calyces and resorption of urine - fornical reflux!).

Obstructive acute pyelonephritis (occlusion of the ureter by a stone, products of chronic inflammation of the kidney, external compression - retroperitoneal fibrosis, cancer of the internal genital organs, enlarged lymph nodes, etc.) begins with gradually increasing or acute pain in the lower back on the affected side, followed by chills and increased body temperature.

Complications of obstructive acute pyelonephritis:

• development of a purulent process;
• severe impairment of renal function;
• bacteriotoxic shock;
• urosepsis;
• toxic hepatitis;
• paranephritis;
• pyonephrosis.

Diagnostics

When collecting anamnesis, pay attention to:

• for recent hypothermia;
• chronic pyelonephritis;
• urolithiasis;
• diseases of the female genitalia, prostate gland;
• previous operations on the kidneys and urinary tract, etc.

They check that the pulse rate corresponds to body temperature, detect pain in the hypochondrium during palpation of the abdomen and a positive symptom of tapping on the lower back (Pasternatsky’s symptom) from the affected kidney.

Laboratory diagnostics. In a general urine test, leukocyturia is often noted, which may be absent in obstructive acute pyelonephritis, since urine from the affected kidney does not enter the bladder.

In a general blood test, leukocytosis is noted, often with a shift in the blood count to the left (the number of band neutrophils is 20% or higher).

In a biochemical blood test, an increase in urea and creatinine levels is possible, often in elderly and weakened patients, with chronic renal failure or damage to the only functioning kidney.

When culturing urine (carried out before antibacterial therapy), the causative agent of the disease is isolated and its sensitivity to antibacterial drugs is determined.

To clarify the diagnosis and form of acute pyelonephritis, the following is carried out:

• Ultrasound;
• X-ray examinations;
• computed tomography;
• magnetic resonance imaging.

Acute pyelonephritis is differentiated from the following conditions:

• infectious diseases that occur with fever and chills and are not accompanied by pain localized in the lumbar region;
• surgical pathology of the abdominal organs, in which severe pain is often observed, and a pronounced increase in temperature and dysuric phenomena are rare.

Main directions of therapy

The emergency care algorithm for acute pyelonephritis is presented in Figure 2.

1. Normalization of urine passage from the kidney:
   installation of a ureteral catheter or stent;
2. installation of a catheter in the bladder if vesicoureteral reflux is suspected (lower back pain during urination);
3. nephrostomia.
4. Antibacterial therapy for acute pyelonephritis is in most cases empirical and depends on the severity of the disease:
   mild - oral drugs from the fluoroquinolone group;
5. moderate and severe - parenteral aminoglycosides in combination with or without ampicillin, fluoroquinolones, third and fourth generation cephalosporins in combination with or without aminoglycosides.
6. Surgical treatment after further examination is prescribed:
   if antibacterial therapy is ineffective within 3 days;
7. severe course of the disease;
8. purulent pyelonephritis

Clinical pharmacology of individual drugs

Gentamicin is effective against infections caused by gram-positive and gram-negative microorganisms, bacteria of the intestinal group. The drug is rapidly absorbed when administered intramuscularly, the therapeutic concentration in the blood is reached after 1 hour and persists for 8–12 hours. A single dose is 80–160 mg, a daily dose is 160–320 mg. Side effects: nephro- and ototoxicity. Contraindications for use: decreased kidney function and decreased hearing.

Fluoroquinolones (ciprofloxacin, norfloxacin, ofloxacin) are active against a large number of gram-positive and gram-negative bacteria and are available in forms for oral and parenteral administration. The drugs are well absorbed in the intestine and widely distributed in body fluids and tissues, secreted mainly by the kidneys. The half-life is 3–7 hours. The most widely used drugs for the treatment of acute pyelonephritis are ciprofloxacin (medociprin, siflox, ciprovin) - 500 mg 2 times a day, norfloxacin (nolicin, norbactin) - 400 mg 2 times a day and ofloxacin (zonocin, oflo , ofloxacin) - 200 mg 2 times a day. The use of fluoroquinolones is contraindicated in children under 14 years of age, pregnant women, as well as in case of individual intolerance.

Common therapy errors:

• conservative management of obstructive pyelonephritis;
• continuation of intensive antibacterial therapy without effect for more than 3 days without further examination;
• prescription of antibacterial drugs from the group of semisynthetic penicillins (ampicillin, oxacillin);
• the use of drugs from the group of uroseptics (nitroxoline, palin, negram, etc.).

Indications for hospitalization are most cases of acute pyelonephritis, especially if there is a suspicion of an obstructive nature of the lesion.

Analysis of clinical cases

Patient S., 18 years old. Complaints of pain in the left lumbar region, increased body temperature to 38°C, accompanied by chills, nausea, increased frequency and painful urination. History: 3 days ago there was hypothermia, after which urination became more frequent and painful, the temperature increased and pain appeared. I took nitroxoline without effect. On examination: pain on palpation in the left lateral parts of the abdomen, Pasternatsky’s sign is sharply positive on the left. Diagnosis: acute non-obstructive pyelonephritis on the left. The patient was hospitalized in the urological hospital. Treatment: antibacterial therapy with gentamicin (80 mg 2 times a day IM).

Patient K., 29 years old. Complaints of sharp pain in the right lumbar region, radiating to the perineum, increased body temperature to 39°C with tremendous chills, nausea, and repeated vomiting. Medical history: he has been suffering from urolithiasis for a long time; previously, small stones passed on their own several times. Two days ago, sharp pain appeared in the right lumbar region, she took Baralgin and No-shpa with a temporary effect. A day after the onset of pain, she noted a rise in temperature with chills, nausea and vomiting. On examination: the patient groans in pain. The tongue is dry, heart rate 90 beats/min. The abdomen is soft, sharply painful on palpation in the right lateral regions, Pasternatsky's symptom is sharply positive on the right. Diagnosis: right-sided renal colic. Acute obstructive pyelonephritis on the right. The patient was hospitalized in the urological hospital. Treatment: catheterization of the right ureter; if this is impossible, nephrostomy on the right. Intensive detoxification and antibacterial therapy.

Patient Sh., 67 years old. Complaints of chills, increased body temperature to 39.5°C, lower back pain on the right. History: 3 months ago, a radical cystoprostatectomy was performed for bladder cancer, plastic surgery of the bladder with an intestinal flap according to Studer. Preoperative examination revealed aplasia of the left kidney in the patient. A month after the operation, constant nagging pain appeared in the right lumbar region; he did not consult a doctor. Over the past week, the amount of urine excreted has decreased and swelling of the legs has appeared. Three days ago he noticed an increase in temperature against the background of increased pain in the right lumbar region, the temperature progressively increased, reached 39.5°C and was accompanied by chills, the volume of urine per day did not exceed 200 ml. On examination: the patient is pale, asthenic in build, and there is swelling of the lower extremities. Palpation reveals severe pain in the right lateral parts of the abdomen, Pasternatsky's symptom is sharply positive on the right. Diagnosis: acute obstructive pyelonephritis on the right. Stricture of the right ureteroneocystanastomosis. Oliguria. The patient was hospitalized in the urological hospital. Treatment: emergency nephrostomy on the right.

Hematuria is a pathological symptom characterized by blood in the urine.

The main causes of renal bleeding are presented in Table 1.

Essential hematuria (Table 2) combines a number of conditions in which the etiology and pathogenesis are unknown, and clinical, radiological and morphological studies do not allow us to accurately indicate the cause of bleeding.

Hematuria can be caused by taking non-narcotic analgesics, anticoagulants, cyclophosphamide, oral contraceptives, vincristine.

With kidney tumors, when the tumor grows in the pelvis or calyces, the integrity of the vascular wall is disrupted. If the tumor does not communicate with the pyelocaliceal system, the venous outflow from the area of ​​the kidney with the tumor node is disrupted, the fornical veins dilate and rupture.

With prostate cancer, the tumor grows into the walls of the bladder or prostatic urethra, the veins of the bladder in its cervical section are compressed by the tumor, and venous stasis occurs. Free-floating villous tumors of the bladder, located near its neck, during urination are carried away by the flow of urine into the urethra, clog its lumen and, when pinched, swell, burst and begin to bleed.

With cystitis and prostatitis, the mucous neck of the bladder becomes inflamed, injured and bleeds easily when it comes into contact with other walls at the end of urination.

When renal hemo- and urodynamics are disturbed, the venous plexuses of the fornix, with impaired venous outflow or a significant increase in intrapelvic pressure, become overfilled with blood, the veins encircling the vaults of the calyces in a ring form expand and their integrity is disrupted, which leads to hematuria from the upper urinary tract.

With necrosis of the renal papillae, the blood supply to the papilla, and sometimes to the entire Malpighian pyramid, is disrupted, necrotic tissue is rejected, and bleeding occurs.

With benign prostatic hyperplasia, venous congestion occurs in the pelvic organs, and the integrity of the vessels is disrupted.

There are two types of hematuria:

• microscopic - the presence of red blood cells in the urine (more than three in the field of view) is determined only by microscopic examination of urine sediment;
• macroscopic - blood in the urine is determined visually; if only in the first portion of urine - initial (initial), in the last portion of urine - terminal (final), in all portions of urine - total.

Clinical picture

The appearance of red blood cells in the urine gives it a cloudy appearance and a pink, brown-red or reddish-black color, depending on the degree of hematuria. Hematuria can occur suddenly, be one-time or repeated. Its cessation is deceptive, since the cause of hematuria, as a rule, is not eliminated, and examination in case of repeated bleeding with a great delay often reveals an already advanced tumor.

With a kidney tumor, hematuria may be the first and for a long time the only symptom of the disease. In most cases, it is painless, but with profuse bleeding with the formation of clots in the renal pelvis and their passage through the ureters, dull, less often colicky pain occurs in the lumbar region. With papillary tumors of the bladder, hematuria is usually painless and profuse without the formation of clots. With villous tumors of the bladder located near its neck, the urine stream may be interrupted during urination.

With tuberculous kidney damage, total hematuria is observed in the very early stages of the process, which may be accompanied by persistent pyuria.

With benign prostatic hyperplasia, hematuria occurs for no apparent reason or during catheterization of the bladder due to a violation of the integrity of the loosened mucous membrane of the posterior urethra.

In acute cystitis and prostatitis, terminal hematuria is noted against the background of severe dysuria.

With urolithiasis, hematuria usually develops following an attack of renal colic; the urine stream may suddenly stop during urination.

Possible complications: with massive bleeding with the formation of shapeless clots, acute urinary retention is possible due to tamponade of the bladder with these clots. Rarely, shock may develop due to blood loss and pain.

Diagnostics

During the survey you need to find out:

• conditions for the occurrence of hematuria;
• degree, nature and duration of hematuria: - initial hematuria - a pathological process in the urethra (tumor, inflammation, foreign body, burn, etc.); – terminal hematuria - a pathological process in the neck of the bladder (acute cystitis, prostatitis, stones and bladder tumors); – total hematuria is a pathological process in the kidney, ureter or bladder (tumors, benign prostatic hyperplasia, renal tuberculosis, pyelonephritis, necrosis of the renal papillae, nephroptosis, etc.);
• the presence of blood clots in the urine, their shape: – worm-shaped – bleeding from the upper urinary tract and the formation of clots in the ureter; – shapeless clots – bleeding from the bladder;
• the presence of pain and its connection with changes in the color of urine: – pain in the lumbar region on the affected side – disruption of the passage of urine from the kidney due to blood clots, urolithiasis; – painless hematuria with subsequent development of renal colic (normal-colored urine) – tumor of the kidney or upper urinary tract;
• presence or absence of dysuric phenomena;
• whether there were injuries to the kidneys, bladder, urethra (in case of injury, blood is released from the urethra outside the act of urination).

Visual assessment of urine:

• scarlet blood - bleeding continues;
• brown urine - bleeding has stopped;
• brick shade - intense uraturia.

The color of urine may change when taking medications and foods:

• pink - when taking pyramidon;
• saffron yellow - nitroxoline;
• brown - rhubarb and hay;
• raspberry - purgena;
• red - phenolphthalein and beets;
• red-brown - madder dye.

With the syndrome of prolonged compression and crushing of tissues, myoglobin from the muscles enters the blood and penetrates into the urine, which gives it a red-brown color.

To determine the nature and source of bleeding in a hospital setting, the following is carried out:

• cystoscopy - in all cases of gross hematuria, with the exception of inflammatory diseases (acute urethritis, cystitis, prostatitis);
• digital rectal examination;
• Ultrasound of the bladder kidneys, prostate, transrectal ultrasound;
• excretory urography, retrograde reno- and urethrocystography, computed tomography, osteoscintigraphy according to indications in a hospital setting.

Laboratory diagnostics include:

• clinical analysis of blood, urine;
• blood chemistry;
• microscopic examination of urine sediment;
• urine culture for sterility;
• determination of the level of prostate-specific blood antigen.

With hemoglobinuria, the color of urine does not change even after standing for a long time, and with hematuria, red blood cells settle to the bottom of the vessel and the upper layers of urine become yellowish.

Hematuria in women should be differentiated from bleeding from the genitals. To do this, examine the average portion of urine during spontaneous urination or urine obtained from the bladder by catheterization.

Main directions of therapy

The emergency care algorithm for hematuria is presented in Figure 3.

With the development of hypovolemia and arterial hypotension, restoration of bcc: crystalloid and colloid solutions intravenously.

If acute cystitis is suspected, after collecting urine for culture to ensure sterility, a broad-spectrum antibiotic is prescribed.

Therapy with hemostatic drugs should be carried out in a urological hospital, after diagnosis, under the control of blood clotting.

Clinical pharmacology of individual drugs

Etamsylate (dicinone) activates the formation of thromboplastin, the formation of blood coagulation factor III, and normalizes platelet adhesion. The drug does not affect the thrombotic time, does not have hypercoagulable properties, and does not contribute to the formation of blood clots. Etamsylate is administered in 2–4 ml (0.25–0.5 g) intravenously at once or drip, adding to conventional solutions for infusion.

The hemostatic effect develops:

• for intravenous administration - after 5–15 minutes; maximum effect - after 1–2 hours; the effect lasts 4–6 hours or more;
• when administered intramuscularly, the effect occurs somewhat more slowly;
• When taken orally, the maximum effect occurs after 3 hours.

Etamsylate should not be used for hemorrhages caused by anticoagulants.

Aminocaproic acid inhibits fibrinolysis by blocking plasminogen activators and partially inhibiting the effect of plasmin, and has a specific hemostatic effect in bleeding associated with increased fibrinolysis. To quickly achieve an effect, under the control of a coagulogram, a sterile 5% solution of the drug in saline is administered intravenously, up to 100 ml.

Protamine sulfate has an antihemorrhagic effect in bleeding caused by heparin during its overdose, after operations using extracorporeal circulation and the use of heparin. Apply 1 ml of a 1% solution intravenously in a slow stream over 2 minutes or drip; 1 mg of protamine sulfate neutralizes approximately 85 units of heparin. Contraindicated in hypotension, adrenal insufficiency, thrombocytopenia.

Common treatment errors: prescribing hemostatic drugs before identifying the source of hematuria.

Gross hematuria is an indication for emergency hospitalization in a urological hospital.

Analysis of clinical cases

Patient M., 30 years old. Complaints of cramping pain in the lumbar region on the left, aggravated by movement, after physical activity, blood in the urine, increased body temperature to 38.2°C. The disease began with dysuria in the form of frequent, painful urination, a day later pain appeared in the lumbar region, and blood in the urine. History: 7 years ago, a diagnosis was made of stage I nephroptosis on the left. The disease manifested itself as periodic attacks of pyelonephritis. On examination: the patient is restless. The kidney area is visually unchanged, painless on palpation, the effleurage symptom is weakly positive on the left, there is no pain along the ureters, the bladder is empty by percussion. Diagnosis: acute ascending left-sided pyelonephritis. Nephroptosis on the left. The patient was hospitalized in the urology hospital.

Patient J., 77 years old. Calling an emergency room due to intense blood in the urine and the release of blood clots during urination. History: no urological diseases. On examination: the patient is asthenic, the skin is pale. The kidney area is not visually changed; bimanual palpation of the right kidney reveals a mass formation in the lower segment; the effleurage symptom is negative on both sides. A digital rectal examination reveals that the prostate is enlarged 1.5–2 times, has a tight-elastic consistency, the median groove is smoothed, the rectal mucosa above the gland is mobile, palpation is painless. Diagnosis: tumor of the right kidney. The patient was hospitalized in the urology department.

Patient Ch., 24 years old. Complaints of constant bleeding through the urethra. History: About an hour ago I fell and hit my crotch on a pipe. On examination: bruising in the perineal area, discharge of scarlet unchanged blood from the urethra, outside the act of urination. A digital rectal examination reveals that the prostate gland is of normal size, has a tight-elastic consistency, the median groove is pronounced, the rectal mucosa above the gland is mobile, palpation is painless. Diagnosis: urethral injury. The patient is indicated for hospitalization in a hospital for examination and determination of treatment tactics.

Thus, the success of treatment of patients with pyelonephritis and hematuria is largely determined by the adoption of adequate measures in the provision of emergency medical care.

E. B. Mazo , Doctor of Medical Sciences, Professor, Corresponding Member of the Russian Academy of Medical Sciences, Russian State Medical University, Moscow

Table 1. Causes of renal bleeding

Table 2. Causes of essential renal hematuria

Therapy of despair

The new virus has misled the entire global medical community, researchers and experts. What can we say about the paramedics and doctors who come to our home when called. Patients with Covid are prescribed azithromycin, arbidol, hydroxychloroquine, and other useless, unnecessary or dangerous drugs.

Indeed, it happens that doctors do not know what to prescribe, and they prescribe at least something for the sake of prescribing, to reassure the patient and give him hope that he will recover. Do not forget that they follow the guidelines approved by the Ministry of Health, the schemes of which are used only in Russia.

Photo: Alexander Demyanchuk/TASS

“I started to get the impression that outpatient doctors weren’t just doing this to prescribe. They want to reassure not only the patient, but also to overcome their fear of this infection and their fear of complications that may arise suddenly. It feels like they are trying to use everything, but as a therapy for despair. Thus, they delay the moment of what they believe are complications, and they also gain time for themselves, giving themselves the opportunity to reduce their vigilance towards this patient. So the doctor shifts responsibility to those who created these clinical recommendations.”

There are also those who have not read clinical studies or studied the opinions of the world medical community. Prescriptions by such doctors occur out of ignorance.

Modern anticoagulant therapy for atrial fibrillation

Magazine "Remedium" No. 11–12, 2021

DOI:

10.21518/1561-5936-2020-11-12-28-30

Nadezhda Kalinina,
RM Analytics
Atrial fibrillation (AF) is diagnosed in approximately 2% of people in the general population, and its prevalence is steadily increasing due to the aging population. The most severe complication of AF is stroke, the risk of which can be significantly reduced by taking oral anticoagulants [1].

Modern anticoagulant therapy in atrial fibrillation patients

Nadezhda Kalinina,
“RM Analytics”
The atrial fibrillation (AF) is detected in almost 2% of the general population, and its prevalence is continuously rising as the population is aging. Stroke is the most severe complication of AF and its risk can be significantly reduced by using oral anticoagulants [1].

Until recently, warfarin was practically the only option for long-term anticoagulant therapy in patients with non-valvular AF and venous thromboembolic complications, as well as other diseases that necessitate long-term use of anticoagulants. However, the use of warfarin in clinical practice is complicated by numerous drug and food interactions, as well as the need for constant monitoring of coagulation parameters. The presence of these significant disadvantages in warfarin therapy has prompted the scientific community to create an alternative to warfarin. This is how direct oral anticoagulants (DOACs) were created, which at the moment, according to the 2021 clinical guidelines for AF, are first-line drugs for non-valvular atrial fibrillation [2]. Drugs of this group registered in the Russian Federation are rivaroxaban (Xarelto®), apixaban (Eliquis®) and dabigatran etexilate (Pradaxa®) [2].

According to IQVIA data, based on the results of 9 months. In 2021, the leader in the ATC group B01 “Antithrombotic drugs” in terms of sales volume was the drug Xarelto® (INN rivaroxaban), reaching 12.7 billion rubles, which is equivalent to 3.7 million packages ( Table 1

).

Table 1. Top 5 by sales volume of drugs in the ATC group of the 2nd level B01 “Antithrombotic drugs”, January – September, 2020

Source: IQVIA, all channels (wholesale prices)

Moreover, analysis of the anticoagulant market ( Table 2

) for the first 9 months. 2021 and 2021 showed a significant increase in sales of anticoagulants in the amount of 11.96 billion rubles, with more than 60% of the increase accounting for the preferential segment (+8.13 billion rubles).

Table 2. Analysis of the anticoagulant market, 2019–2020, rub.

* Analysis period: January – September of the corresponding year.

Data source: IQVIA research report

At the same time, Xarelto® not only continues to occupy a leading position in preferential drug provision, but also increased its share in the total volume of anticoagulants for the first 9 months. 2021, reaching a market share of 53% ( Fig. 2

).

Xarelto® is an oral direct factor Xa inhibitor used for the prevention of stroke and systemic embolism in patients with non-valvular AF, for the treatment and prevention of deep vein thrombosis and pulmonary embolism, as well as for other indications [3–5].

Xarelto® is the leader in sales among DOACs and has a wide evidence base in various clinical situations. The favorable efficacy and safety profile of Xarelto® is due to a reduced risk of stroke/systemic embolism and life-threatening bleeding compared with warfarin in patients with non-valvular AF, incl. elderly and senile age, as was demonstrated in the large randomized clinical trial ROCKET AF and studies of real clinical practice [6–7].

Confidence based on RCT data, a wide program of prospective observational studies with high evidentiary value and own experience of using the drug by doctors of various specialties contributed to the fact that Xarelto became the most prescribed DOAC in Russia1 [8].

Additionally, Xarelto is the only DOAC that, when added to acetylsalicylic acid (ASA), has been shown to reduce the risk of major cardiovascular events, cardiovascular death, and all-cause death in patients with stable coronary artery disease or peripheral artery disease compared with ASA monotherapy [9]. In addition, Xarelto® is also the only DOAC registered in the Russian Federation for use after acute coronary syndrome, which occurred with an increase in the level of cardiac-specific biomarkers, with the aim of preventing cardiovascular events and death from them [3, 10].

Traditionally, in the vast majority of cases, patients in need of antithrombotic therapy purchase drugs at their own expense, with the exception of a small category of patients entitled to free drugs under the federal ONLP program or the regional RLO program [11, 12]. In 2021, Xarelto®'s share of subsidized sales was 48%, while the share of other DOACs was significantly smaller (35% for Pradaxa® and 5% for Eliquis®) in the overall anticoagulant market ( Fig. 1

).

Figure 1. Distribution of sales of anticoagulants in the preferential market segment in 2021, % (January – September)

Data source: IQVIA research report

However, in order to reduce cardiovascular mortality and increase average life expectancy, since January 2021, a program (hereinafter referred to as the Program) for the secondary prevention of cardiovascular events among patients who have suffered acute cerebrovascular accident (ACVA: strokes and transient ischemic attacks) has been launched in the Russian Federation ), myocardial infarction, as well as after cardiovascular interventions (coronary artery stenting, coronary artery bypass grafting and catheter ablation) [13]. For a year after the event or surgery, patients receive drug therapy free of charge.

Within the framework of the Program, Xarelto® is the only DOAC with an indication for the prevention of not only stroke among patients with AF, but also cardiovascular events and death from them in patients without AF after ACS, as well as for the prevention of atherothrombotic complications and death in patients with ischemic heart disease. heart disease or peripheral arterial disease [3–5, 14]. Due to the breadth of indications, proven clinical benefits that provide comprehensive protection for patients with high cardiovascular risks, as well as ease of use that promotes high adherence to therapy, Xarelto® has become the leader in terms of purchase volume within the Program and in the drug benefit channel in general ( Fig. 2

).

Figure 2. Distribution of sales of anticoagulants in the preferential segment of the market in 2021, % (January – September)

Data source: IQVIA research report [15]

The development and implementation of such programs is a significant step towards the further development of the cardiovascular risk management system in the country, which is aimed at the efficient use of healthcare resources and reducing cardiovascular mortality in the Russian Federation.

1 For the period of 2021, Xarelto® overall ranks first in the prescriptions of doctors of the following specialties: cardiologists, surgeons, internists/general practitioners - in 21 cities of the Russian Federation among the ATX brands “B01A A Vitamin K Antagonists”, “B01A F Direct Factor Xa Inhibitors " and "B01A E Direct thrombin inhibitors."

List of literature / References

1. Kanorsky S.G. The use of rivaroxaban in real clinical practice: results of a prospective observational study of xanthus in patients with atrial fibrillation. Rational pharmacotherapy in cardiology
   . 2016;12(4):443–449.
2. Rubricator of clinical recommendations of the Ministry of Health of the Russian Federation. Atrial fibrillation and flutter. 2021.
3. Instructions for medical use of the drug Xarelto® 20/15 mg (dated 04/27/2020).
4. Instructions for medical use of the drug Xarelto® 10 mg (dated 07/16/2020).
5. Instructions for medical use of the drug Xarelto® 2.5 mg (dated May 22, 2020).
6. Patel MR, Mahaffey KW, Garg J. et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med
   . 2011;365(10):883–891. doi: 10.1056/NEJMoa1009638.
7. Hanon O., Vidal J., Pisica-Donose G. et al. Bleeding risk with rivaroxaban compared with vitamin K antagonists in patients aged 80 years or older with atrial fibrillation. Heart
   . 2021. doi: 10.1136/heartjnl-2020-317923.
8. Audit data of medical prescriptions RxTest™ database “Market research system “Pharmxplorer”. RxTest™ is an expert-analytical product of sociological research among an audience of doctors from 17 specialties in 21 cities of the Russian Federation.
9. Eikelboom JW, Connolly SJ, Bosch J. et al. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med
   . 2017;377(14):1319–1330. doi: 10.1056/NEJMoa1709118.
10. Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med
    . 2012;366(1):9-19. doi: 10.1056/NEJMoa1112277.
11. Federal Law “On State Social Assistance” dated July 17, 1999 No. 178-FZ.
12. Decree of the Government of the Russian Federation of July 30, 1994 No. 890 “On state support for the development of the medical industry and improving the supply of medicines and medical products to the population and healthcare institutions.”
13. Decree of the Government of the Russian Federation dated November 30, 2019 No. 1569 “On amendments to the state program of the Russian Federation “Healthcare Development. Appendix 11 “Rules for the provision and distribution of subsidies to ensure the prevention of the development of cardiovascular diseases and cardiovascular complications in high-risk patients undergoing dispensary observation, to the budgets of the constituent entities of the Russian Federation for 2021 and for the planning period of 2021 and 2022.”
14. Order of the Ministry of Health of the Russian Federation dated 01/09/2020 No. 1n “On approval of the list of medications, which are provided through subsidies from the federal budget to ensure the prevention of the development of cardiovascular diseases and cardiovascular complications in high-risk patients undergoing dispensary observation.”
15. Analysis of the anticoagulant market. IQVIA
    . 2021.

Coronavirus therapy now [RECOMMENDATIONS] First aid kit for Covid

These recommendations from our expert should only be used after consultation with your doctor.

• If possible, buy a pulse oximeter and monitor your saturation readings.
• Of the medications, first of all, it is necessary to have any antipyretics. The WHO warning that some antipyretics worsen the course of the new coronavirus infection has now been completely debunked. This warning was withdrawn back in March.
• You can also use any usual painkillers (in the absence of individual contraindications).
• For those taking birth control pills or who have a tendency to clot, it is necessary to have anticoagulants. These are drugs that thin the blood and prevent the formation of blood clots.
• When taking anticoagulants and antipyretics, you need to remember to protect the stomach (omeprazole, famotidine, etc.) to avoid gastrointestinal bleeding.
• If you have a new coronavirus infection, you should drink more fluids to prevent dehydration and kidney problems.

Do not forget that the doctor must explain to the patient what he is prescribing and why.

*Based on materials from Oksana Stanevich’s broadcast for the “Not in vain” foundation and personal consultation for the “SP” publication.

Active substance and mechanism of action

The composition of “Curantil” includes a substance – dipyridamole, which affects the condition of blood vessels and blood.

Dipyridamole has a complex effect on the circulatory system:

• stimulates blood circulation throughout the body;
• prevents varicose veins and thrombosis;
• dilates the walls of small vessels;
• improves heart rhythm;
• increases the body's resistance to viruses.

The content of 25 mg of dipyridamole helps “Curantil” reduce blood pressure. Despite the effective effect of the drug on the bloodstream, the active component does not affect the coronary vessels, eliminating the risk of ischemia.

The drug "Curantil" is based on the action of dipyridamole - the main active substance