For pancreatitis, complex therapy is carried out aimed at restoring normal activity of the pancreas. The patient is prescribed anticholinergics, H2 blockers, antispasmodics, and enzymes. In case of exacerbation of pancreatitis, the use of protease inhibitors is indicated.
These substances slow down the activation of proteolytic enzymes, relieve tissue swelling, reduce the intensity of pain, and prevent the development of a state of shock. One such inhibitor is Gordox. The drug is prescribed to patients who have obstruction of the pancreatic ducts (due to inflammation, trauma or oncology).
If the excretion of pancreatic secretions is impaired, then under the action of cytokinase the inactive enzyme transforms into an active form not in the intestine, but in the pancreas, which provokes autolysis, that is, self-digestion. A protease inhibitor inactivates trypsin and blocks free kinins, that is, prevents the development of a destructive process in the organ.
Use of the drug Gordox
Adults - the initial dose is 500,000 CIU of aprotinin IV slowly (maximum rate 5 ml/min) with the patient lying down. To maintain the achieved level in the blood, administration continues with a long-term drip infusion (200,000 CIED every 4–6 hours). The daily dose is at least 1,000,000 CIED. After improvement of the clinical picture and laboratory parameters, the daily dose can be gradually reduced to 500,000 CIED. For children - the daily dose is 20,000 CIED of aprotinin per 1 kg of body weight per day.
Reviews
Victor: A couple of years ago I was diagnosed with chronic pancreatitis. When the next time of exacerbation comes, only Gordox saves me. Despite the fact that today there are many new alternatives to this drug, I continue to use it because it is more effective than all other analogues.
Lyudmila: When my son had surgery, during rehabilitation he was diagnosed with pancreatitis. Having turned to a doctor for help, he prescribed us intravenous injections of Gordox, which we had to carry out in a hospital setting. The device turned out to be not cheap and we regularly went for procedures. Before use, carefully read the instructions for use and learned that the drug can cause allergic reactions and the development of anaphylaxis. But fortunately, we managed to avoid all this. After 3 injections, his health improved, and no side effects were identified.
Stepan: During an exacerbation, they give me Gordox and in three days I become human again.
Gordox is effective and, according to patients, already on the 2nd day after the start of treatment, the condition improves significantly, the pain syndrome is less pronounced. Since anaphylactic shock may occur during therapy, the drug is prescribed to patients in a hospital setting.
Special instructions for the drug Gordox
The active substance has a protein nature and a polypeptide structure, therefore it can act as an antigen. In order to establish hypersensitivity, before administering the initial dose, it is necessary to administer 1 ml of a test dose from a 10,000-fold dilution intravenously. If an allergic reaction to the test dose occurs, the use of the drug is contraindicated. If hypersensitivity reactions occur during administration of the drug, the infusion must be stopped immediately. In the second and third trimester of pregnancy, the drug can be prescribed only after a thorough assessment of the benefit/risk ratio.
Additional Information
It is allowed to prescribe Gordox to pregnant women in the second trimester. In this case, constant medical monitoring of the health of the mother and child should be carried out. There is no clinical data that would confirm that the drug does not penetrate into mother's milk and does not affect the immature organism, therefore it is not recommended to take a protease inhibitor during lactation.
In case of an overdose of Gordox, the patient may develop an allergic reaction, even anaphylactic shock is possible. If there are signs of intolerance to the drug, then Gordox is discontinued and symptomatic therapy for pancreatitis is carried out.
The drug interacts with some medications, so the drug should be used under the supervision of a doctor
Aprotinit added to heparinized blood leads to an increase in the clotting period. The simultaneous use of Gordox with Reomacrodex enhances the therapeutic effect of both drugs (sensitizing effect).
The active component of the solution suppresses the effect of urokinase, alteplase, streptokinase. It is also a weak inhibitor of serum cholinesterase, therefore, with the simultaneous use of the drug, muscle relaxation increases, and the development of apnea is likely.
Gordox is available in pharmacies with a doctor's prescription. It should be stored at 15–30 ⁰С. Shelf life: 5 years. Before starting a therapeutic course, it is necessary to check whether there is an individual sensitivity to the components of Gordox, so a skin test is performed.
If the patient has had allergic reactions, then before therapy with aprotinin it is necessary to take histamine receptor blockers and corticosteroids. If DIC syndrome and hyperfibrinolysis manifest themselves, then taking Gordox is permissible only when all signs of DIC syndrome have been eliminated and there is a preventive effect of heparin.
Gordox should be taken with caution if muscle relaxants were taken 2-3 days before aprotinin therapy. With a repeated course of treatment with Gordox, the risk of developing severe allergies and anaphylactic shock increases, so people with a predisposition to allergies need to carefully monitor their health and determine the balance of risk and benefit.
Alcohol is used as an excipient in Gordox, so the daily dose should not exceed 90 mg/kg
If the ampoule contains a dose greater than that prescribed by the doctor, then the remainder must be disposed of, since the solution cannot be stored.
Medicines that, like Gordox, contain aprotinin:
- Aprotinin;
- Aprotex;
- Aerus;
- Ingitril;
- Troxolan.
Side effects
As a rule, when using Gordox, patients do not experience any side effects. In rare cases, dyspeptic and allergic effects may occur. in blood pressure occur .
Allergic manifestations are rare during the first administration of the drug; the frequency of their development increases (by approximately 5%) with repeated administration of the drug. The likelihood of severe allergic or anaphylactic manifestations increases if Gordox treatment was carried out twice or more within 6 months.
Introduction
Chronic pancreatitis (CP) is an inflammatory, continuously persistent disease of the pancreas (PG), often associated with pain, which is characterized by the development of irreversible morphological changes in the parenchyma and ductal system of the pancreas and the progressive destruction of organ tissue, leading to disruption of exocrine and endocrine functions [1 , 2].
Several risk factors have been established and/or suspected, but in a small proportion of patients the disease is idiopathic. Clinically, the early phase of the disease is characterized by pain or recurrent exacerbations of pancreatitis and the development of complications, while in the later stages of the disease, symptoms are caused by the appearance of exocrine and/or endocrine insufficiency. Chronic pancreatitis in the late stages is considered a risk factor for the development of pancreatic cancer [3–5], and therefore treatment of CP with conservative, surgical, endoscopic methods, or a combination thereof, can be considered as a putative measure for the prevention of carcinogenesis in the pancreas.
Despite numerous attempts, an ideal system for the etiological classification of CP has not yet been created. An emphasis on the etiology of CP is necessary because it provides an attempt at etiotropic treatment (for example, obstructive pancreatitis) or a more accentuated pathogenetic one when the first option is impossible (for example, treatment with steroids for autoimmune pancreatitis). One of the latest options for systematizing the many etiological factors of CP is the M-ANNHEIM classification of CP risk factors (Multiple, Alcohol, Nicotine, Nutrition, Heredity, Efferent pancreatic duct factors, Immunological factors, Miscellaneous and Metabolic factors) [6].
Alcohol abuse. Alcohol is responsible for 60–70% of cases of CP in the Western world. The dose of daily alcohol consumption at which the risk of developing CP increases has not been established, but according to some estimates, it may be 60–80 ml/day (pure ethanol). Gender, genetic and other factors may play a major role, and as a result, the term “alcoholic pancreatitis” does not necessarily imply chronic alcoholism or the consequences of alcohol abuse. Smoking increases the risk of development and progression of CP [2].
Smoking. The odds ratio for developing CP for smokers compared with non-smokers ranges from 7.8–17.3; The risk increases with the number of cigarettes smoked and the length of smoking. Thus, smoking should be considered an independent risk factor for the development of CP [7, 8].
Nutritional factors. The relationship between protein-energy malnutrition, hypertriglyceridemia, other hyperlipidemias and CP is ambiguous [2].
Hereditary factors. Inherited factors are believed to play a role in hereditary pancreatitis, familial pancreatitis, idiopathic pancreatitis with early and late manifestations, and tropical pancreatitis. Mutations in the coding part of the cationic trypsinogen gene lead to the development of hereditary pancreatitis [9]. In affected individuals, symptoms usually begin before the age of 20 years, and the risk of developing pancreatic adenocarcinoma is markedly increased. Mutations in the coding portion of the cystic fibrosis transmembrane conductance regulatory (CFTR) [10] and trypsin inhibitor (PSTI or SPINK1) [11] gene have been identified in patients with idiopathic CP.
Factors affecting the outflow of pancreatic secretions. Conditions associated with the development of obstructive CP are trauma, the presence of stones, false cysts and tumors. It is not precisely established whether CP occurs against the background of a split pancreas (pancreas divisum) and dysfunction of the sphincter of Oddi [2].
Immunological factors. Autoimmune pancreatitis (AIP) can occur alone or in combination with Sjögren's syndrome, inflammatory bowel disease, and many other autoimmune disorders. Clinically relevant serum findings for the diagnosis of AIP include hypergammaglobulinemia, elevated levels of immunoglobulin G (IgG), especially IgG4, and the presence of certain autoantibodies (antinuclear antibodies, anti-lactoferrin antibodies, anti-carbonic anhydrase type II antibodies, and anti-smooth muscle antibodies) [12]. It is extremely important to identify the etiological form of AIP in patients, since this form of the disease can be treated with corticosteroids.
Other and rare metabolic factors. Chronic renal failure [13] and hyperparathyroidism [14] are established causes of CP, while the exact role of drugs and toxic substances remains completely unproven [2].
Thus, a detailed history is of paramount importance, since its analysis can identify the etiological factor. Particular attention should be paid to occupation, potential exposure to toxic substances, diet, alcohol consumption and smoking. It is appropriate to use validated measures to detect alcohol abuse. Kidney disease and hyperparathyroidism should be considered in the differential diagnosis, and a history of autoimmune disease may indicate the presence of AIP. A thorough family history should be collected, and if a hereditary disease is suspected, genetic counseling is required.
During pregnancy and lactation
Gordox can be used to treat expectant mothers only after the first trimester of pregnancy. However, even in later stages of pregnancy, the drug is used exclusively as prescribed by a doctor and if there are clear indications for its use. At the same time, constant medical supervision is important when treating with this drug.
clinical data on the safety of using the drug during breastfeeding .
pharmachologic effect
The product has an antiprotease and antifibrinolytic effect on the body. Due to the influence of the active substance aprotinin , the activity of a number of proteolytic enzymes is suppressed. Aprotinin is a kallikrein . Under its influence, inflammatory cytokines are released, and the substance also helps maintain glycoprotein homeostasis.
When using aprotinin in surgical practice using AIK, a decrease in inflammatory processes is observed, which, in turn, helps reduce blood loss and also reduces the need for blood transfusion.
Interaction
When aprotinin is added to heparinized blood, an increase in the clotting period of whole blood is observed.
If Gordox is used simultaneously with Reomacrodex , then an increased sensitizing effect is noted.
Aprotinin inhibits the effects of urokinase , streptokinase , alteplase .
Aprotinin is a weak inhibitor of serum pseudocholinesterase. of suxamethonium chloride may slow down , muscle relaxation also increases, and apnea .
Pharmacokinetics and pharmacodynamics
After the drug is administered to the patient intravenously, aprotinin is actively distributed in the intercellular space, as a result of which its concentration in the blood decreases very quickly. The terminal half-life is 5 to 10 hours.
On average, 80% of aprotinin binds to plasma proteins. The drug, which is in free form, determines about 20% of antifibrinolytic activity.
The total clearance is about 40 ml per minute.
The accumulation of aprotinin is mainly observed in the kidneys; less of the substance accumulates in cartilage tissue. A very low concentration of the active substance is observed in the human brain; aprotinin almost does not penetrate into the cerebrospinal fluid. A small amount of the active substance Gordox penetrates the placental barrier.
The active substance is metabolized by lysosomal enzymes in the kidneys; within 48 hours, from 25 to 40% of aprotinin in the urine remains in the form of inactive metabolites.
Diagnostics
It is a very difficult matter, but when stones are visible in the projection of the pancreas during an X-ray of the abdominal cavity, this is considered sufficient to make a diagnosis. But ultrasound is not used to detect chronic pancreatitis because it is not informative; the gland is not visible at all.
CT helps to make a diagnosis and monitor changes in the pancreas, but MRI is much worse in quality.
Endosonography is the same sensitivity as CT - a combination of endoscopy and ultrasound, plus you can immediately take a puncture from the gland. If the instrumental examination is uncertain, functional tests can be performed that indirectly assess the working capabilities of the organ in the later stages, when secretory insufficiency has flourished, but their information content leaves much to be desired.
