Recommendations for prescribing enzyme preparations for syndromes of impaired digestion and absorption

When does the body need help?

Digestion is a complex and long process that involves all organs of the gastrointestinal tract. The leading role in this process is played by enzymes - substances with the help of which food is broken down and absorbed, saturating the body with useful substances. Digestion occurs in several stages, and at each of them, food and drinks encounter enzymes:

1. Once in the mouth - with salivary enzymes.

2. In the stomach - with gastric enzymes.

3. In the small intestine - with pancreatic enzymes.

4. Enzymes from intestinal juice complete the digestion process.

Sometimes at one of the stages a failure occurs due to a lack of enzymes. This is where enzyme preparations come to the rescue. If the digestion process fails, a person may be bothered by:

• heaviness and pain in the abdomen;
• flatulence;
• nausea, heartburn, belching;
• diarrhea, remains of undigested food in the stool.

Such symptoms can accompany many diseases of the gastrointestinal tract, so to clarify the diagnosis and prescribe treatment, you must consult a doctor.

The activity of enzyme preparations
largely depends on factors such as intraduodenal pH and small intestinal motility, which ensure optimal duration of contact of enzymes with food chyme. When the pH in the duodenum decreases to less than 4, lipase is irreversibly inactivated, and trypsin is less than 3.5. At pH less than 5, precipitation of bile salts is observed, which is accompanied by impaired emulsification of fats, a decrease in the number of micelles of bile and fatty acids and a decrease in their absorption.

The main causes of duodenal acidification are increased secretion of hydrochloric acid and decreased secretion of bicarbonates. In these cases, together with enzyme preparations, H2-histamine receptor blockers (ranitidine, famotidine) or proton pump inhibitors (omeprazole, lansoprazole, pantoprazole, rabeprazole) are used to increase intraduodenal pH. Doses of drugs and duration of treatment are determined individually depending on the leading mechanism of this disorder. Motility disorders of the small intestine are also accompanied by impaired mixing of enzyme preparations with food chyme, which reduces their effectiveness. The use of microtablets and microspherical drugs (pancitrate, Creon, lycrease), as well as additional prescription of drugs that normalize intestinal motility (antispasmodics, prokinetics), can significantly improve treatment results.

In case of dysbiosis of the small intestine, the effectiveness of enzyme therapy can be increased by prescribing eubiotics to decontaminate the small intestine.

The choice of combined enzyme preparations is important when diseases of the biliary system and liver are combined with digestive disorders. However, it must be remembered that the use of drugs with bile acids can increase intoxication in severe chronic hepatitis and cirrhosis. In case of chronic diarrhea syndrome, in conditions of secondary malabsorption of bile acids in the intestine, their additional administration can increase diarrhea. In patients with duodenogastric reflux, the use of enzyme preparations containing bile acids (festal, digestal, panzistal, etc.) is inappropriate, since under these conditions bile acids increase the damaging effect of reflux on the gastric mucosa. It has now been established that during exacerbation of chronic pancreatitis, enzyme replacement therapy promotes reverse inhibition of gland secretion, reducing hypertension in the ducts, resulting in an analgesic effect.

It is important to consider that in case of chronic pancreatitis, enzyme preparations should not reduce the pH of the stomach, stimulate pancreatic secretion and increase diarrhea. The drugs of choice in such cases are those that do not contain bile and extracts of the gastric mucosa (pancreatin, somilase, solizym, trienzyme, creon, pancitrate, etc.). In hyperacid conditions, the inclusion in complex therapy of dosage forms containing components of gastric juice (panzinorm) is pathogenetically unjustified. The use of panzinorm for hyperacid gastritis and peptic ulcers increases the activity of proteolytic enzymes and increases the acidity of the stomach, which can clinically manifest itself as a debilitating symptom such as heartburn.

To correct creatorrhea, smaller doses of drugs are required, since the secretion of pancreatic proteases remains preserved for a long time even with pronounced structural changes in the pancreas. In addition, in enzyme preparations taken orally, the activity of lipase and then proteases decreases first. Enzyme preparations for CP with exocrine insufficiency are prescribed for a very long time, often for life. Their doses can be reduced when following a strict diet with limited fat and protein and should be increased when the diet is expanded.

The effectiveness of treatment with enzyme preparations

assessed clinically and by laboratory diagnostic methods.
In this case, the most informative are scatological examination of feces and tests based on determining the excretion of fat in feces. Research is carried out using the Van de Kamer method (quantitative determination of fats in feces), infrared spectrophotometry, radioisotope and other methods. Currently, the elastase test is widely used to assess exocrine pancreatic insufficiency. Unlike existing non-invasive tests, the elastase test can detect endocrine pancreatic insufficiency already in the early stages of the disease. Elastase in feces most reliably reflects exocrine pancreatic insufficiency, because unlike other enzymes, it is not inactivated during transit through the intestines. The standard elastase coprology test contains monoclonal antibodies to human pancratic elastase. Tolerability and side effects
Side effects when using enzyme preparations are extremely rare (less than 1%) and are most often dose-dependent. Increased levels of uric acid may be observed in the urine of patients using high doses of pancreatic enzymes. Hyperuricosuria promotes the precipitation of uric acid in the tubular apparatus of the kidney, creating conditions for the development of urolithiasis. Patients with cystic fibrosis who use high doses of pancreatic enzymes for a long time may develop interstitial fibrosis. With celiac disease, against the background of atrophy of the mucous membrane of the small intestine, the exchange of purine bases in the blood of patients changes sharply with the accumulation of high concentrations of uric acid and an increase in its excretion. Enzyme preparations are used with caution in patients with gout. In some cases, patients taking enzymes may experience diarrhea, constipation, discomfort in the stomach, nausea, and irritation of the perianal area. The main contraindications for prescribing enzyme preparations containing bile components are acute and chronic pancreatitis, acute and severe chronic liver diseases, diarrhea, inflammatory bowel diseases, a history of allergic reactions to pork or beef.

Thus, therapy with enzyme preparations should be carried out differentiatedly, taking into account the mechanism of development of the disease underlying the digestive disorder. The availability of highly active microtablets and microgranular preparations at the doctor’s disposal can significantly increase the effectiveness of enzyme treatment.

Literature:

1. Grebenev A.L., Myagkova L.P. Intestinal diseases. M., 1994.- 397 p. 2. Grigoriev P.Ya., Yakovenko A.V. Reference Guide to Gastroenterology. M., 1997.- 476 p. 3. Zlatkina A.R., Belousova E.A., Nikitina N.Yu., Sileverstova T.R. Modern enzyme therapy of chronic pancreatitis. Ross. journal of gastroenterol., hepatol., coloproctol., 1997.- No. 7 (5).- P. 109-111. 4. Ivashkin V.T., Minasyan G.A. Treatment of chronic pancreatitis. Ross. journal of gastroenterol., hepatol., coloproctol., 1996.- No. 5 (4) - pp. 10-17. 5. Kokueva O.V. Treatment of chronic pancreatitis. - Krasnodar, 2000. - 48 p. 6. Yakovenko E.P. Enzyme preparations in clinical practice // Klin. Pharmacol.1998, V.7 No. 1.- P.1-5.

Enzyme preparations that improve digestion: what are they?

All enzyme preparations described in the article are needed for only one thing: replacement therapy. Replacement therapy is an attempt, using artificially introduced compounds into the body, to supplement the lack of physiological function, a kind of “prosthesis” of the digestive system. Enzymes are highly active and can improve not only intestinal but also gastric digestion.

Enzymes for improving digestion began to appear en masse in clinical practice and in pharmacies back in the 1970s. They are produced in the form of tablet preparations, all are well stored, and can be used both individually and in complex therapy for diseases of the pancreas, mild and severe diseases of the intestines, biliary tract, stomach and liver.

Modern enzyme preparations can be used in newborns, children, and adults. But still, the most common consumers of enzymes will be the elderly and the elderly, since for known reasons of general weakening of vital functions, both the digestive function of the stomach and the enzyme-secreting function of the pancreas are weakened. Their intestinal motility also suffers. What is included in modern enzyme preparations?

Chronic pancreatitis and other conditions

Chronic pancreatitis and other conditions
Pancreatic enzyme medications are among the most commonly used medications. This is due to two factors: the high prevalence of indigestion and their negative impact on the quality of life and the safety of these drugs (close to physiological).

The most important and most motivated indication for prescribing pancreatin drugs is the absence of exocrine (digestive) pancreatic enzymes, when replacement therapy with these enzymes is required.

Complete (true) pancreatin deficiency most often occurs in patients with chronic pancreatitis. It is worth remembering that overdiagnosis of chronic pancreatitis is a common occurrence in clinical practice.

It has been found that the exocrine reserve of the pancreas is very high, so pancreatin (digestive enzyme) deficiency becomes clinical (symptomatic) only when the pancreatic tissue is severely damaged.

Special studies show that symptoms of exocrine pancreatic insufficiency occur in about 90% of patients. The parenchyma of the pancreas, and its remaining functionally active tissue, is not able to satisfy the need for enzymes necessary for digestion.

Chronic pancreatitis is not a common disease. Most often (up to 75-80% of cases), it occurs in people with chronic alcoholism. Research shows that signs of chronic pancreatitis (including enzyme deficiency) occur within an average of 10 years of continuous alcohol consumption. What in everyday life (sometimes in everyday clinical practice is called “chronic pancreatitis”) often turns out to be a digestive disorder of another etiology, including psychogenic, functional.

The use of digestive enzymes in gastroenterological practice

P

Digestive enzymes are widely used for various gastroenterological pathologies.
Enzymes are actively used for various diseases of the stomach, small and large intestines, biliary tract and pancreas. Indications for the appointment of enzyme therapy
are disorders of the secretion of endogenous enzymes, disorders of absorption of nutrients and disorders of motility of the gastrointestinal tract. Currently, the global pharmaceutical industry produces a large number of enzyme preparations (Digestal, Creon, Mezim-Forte, etc.), which differ from each other both in the dose of digestive enzymes they contain and in various additives (see table). Digestive enzymes are available in various forms: tablets, powder or capsules containing enteric-coated microgranules. All enzyme preparations differ in their composition: containing pancreatin (pancreatic extract, usually of pork origin) or digestive enzymes, plant origin, extract of the gastric mucosa. The composition of the drug, in addition to enzymes, may include components of bile, gastric mucosa or adsorbents (simethicone or dimethicone).

Choice of drug

for the treatment of a patient with gastroenterological pathology should be based on the following indicators:

• absolute and relative content of enzymes in the drug (a high content of proteases is indicated for patients with decreased gastric secretion and a painful form of chronic pancreatitis; an increase in lipase activity is necessary for replacement therapy for pancreatic insufficiency);

• the presence of a shell that protects enzymes from digestion by gastric juice;

• the size of the tablet or granules filling the capsules (evacuation of the drug from the stomach simultaneously with food occurs if the size of its particles does not exceed 2 mm);

• the presence of bile acids in the composition of the drug (bile acids improve the digestion of lipids, increase the absorption of fatty acids and cholesterol, and cause increased pancreatic secretion). However, high levels of bile acids in the intestine during intensive enzyme therapy can cause hologenic diarrhea.

Digestive enzymes are indicated for patients with gastric secretion disorders

(hypo- and anacid chronic gastritis, conditions after gastrectomy). After surgical intervention on the stomach, malabsorption syndrome may develop, which is associated with a large number of different factors: a decrease in the production of hydrochloric acid and pepsin; violation of chyme mixing and mechanical processing; disruption of the fractional flow of chyme into the small intestine; acceleration of passage through the small intestine; decreased endogenous stimulation of pancreatic secretion; asynchronous flow of pancreatic juice, bile and chyme into the small intestine [17]. Treatment of post-gastroresection disorders requires complex therapy using antacids, agents that affect gastrointestinal motility, and digestive enzymes.

In hypoacid conditions accompanied by a decrease in the availability of nutrients, preparations containing bile are indicated. These drugs help increase the production of bile and pancreatic juice; they should be taken 1-3 tablets during or immediately after meals (without chewing) 3-4 times a day in courses of up to 2 months.

Preparations containing bile should be used with caution in patients with chronic hepatitis or cirrhosis of the liver, since bile acids enter the liver via the enterohepatic route, where they are metabolized, as well as in cholestatic diseases, peptic ulcers, Crohn's disease and ulcerative colitis.

Hypoacid gastritis is an indication for the prescription of drugs containing components of the gastric mucosa: pepsin and hydrochloric acid. These components provide mechanical and chemical processing of food, primarily proteins. Proteolysis occurs to the level of polypeptides, which are then broken down by pancreatic proteases and partially to amino acids. Pepsin stimulates pancreatic secretion and is therefore contraindicated in patients with chronic pancreatitis, especially in the presence of intraductal hypertension. Preparations containing pepsin are taken at the rate of 0.2–0.5 g of pepsin per meal, 2–3 times a day before or during meals. Recently, for the treatment of patients with a decrease in the acid-forming function of the stomach, drugs containing pure pancreatin, 1 t (4 times a day at the beginning of meals), have been successfully used.

For the treatment of hypomotor dyskinesia (hypokinesia) of the biliary tract

and disorders of fat solubilization, enzyme preparations containing bile acids are successfully used. Bile acids and salts increase the contractile function of the gallbladder and normalize the biochemical properties of bile.

Treatment of pancreatitis with severe pain

requires strict restriction of diet, prescription of antisecretory agents, antispasmodics and pure pancreatin preparations in high doses.
These remedies are the most universal for normalizing digestion in the gastrointestinal tract and can be used as part of complex therapy for all types of disorders. Enzyme products containing pure pancreatin contain proteases, amylase, and lipase. The drug Digestal
contains hemocellulase, which ensures the breakdown of cellulose. Modern research shows that digestive pancreatic enzymes in the traditional non-enteric form provide pain relief during exacerbation [20]. The entry of pancreatic enzymes (primarily trypsin) into the duodenum destroys the releasing peptides of secretin and cholecystokinin and causes a decrease in pancreatic secretion, ensuring functional rest of the organ (Fig. 1).

Rice. 1. Regulation of pancreatic secretion using releasing peptides (according to Li Y., Owyang C., 1996)

Much hope has been associated with digestive enzymes of plant and fungal origin, primarily due to the high acid resistance of plant and fungal lipases. However, under experimental conditions, bacterial lipase turned out to be 75 times less active than pork lipase, and therefore these drugs have not yet found use in clinical practice. Pancreatin does not affect gastrointestinal motility, bile secretion, or bile duct function.

Replacement therapy for exocrine pancreatic insufficiency

necessary for various diseases when atrophy of more than 90% of the organ parenchyma occurs [19] (Fig. 2), occurring most often in the late stage of chronic pancreatitis. Indications include steatorrhea (fat loss in feces more than 15 g/day, with a normal rate of up to 7 g/day), progressive weight loss, diarrhea, and dyspeptic symptoms. Treatment of exocrine pancreatic insufficiency still remains a challenge. Currently, therapy in several areas can be considered the most established: avoiding alcohol consumption, following a diet with frequent small amounts of food, enzyme replacement therapy, combating vitamin deficiency, analgesics (paracetamol, tramadol), psychotropic drugs.

Rice. 2. Etiology of exocrine pancreatic insufficiency

Enzyme therapy for the development of exocrine pancreatic insufficiency requires the use of capsules containing microgranules (microtablets) of pancreatin. In case of disturbances in the hydrolysis of nutrients, capsules are significantly more effective than regular-sized pancreatin tablets. The peculiarity of these drugs is that the enzymes they contain are released only in the alkaline environment of the small intestine and thus avoid destruction by gastric juice (Fig. 3), which significantly increases the effectiveness of replacement therapy for pancreatic steatorrhea. The stability of the drug in an acidic environment is a very important property of the drugs (the main components of enzyme preparations - lipase and trypsin quickly lose activity in an acidic environment: lipase at pH = 4, trypsin at pH = 3; before the drug enters the duodenum, up to 92% of the lipase can be destroyed ). This property significantly increases the effectiveness of replacement therapy and reduces or eliminates the need to prescribe drugs that block gastric secretion. Thus, when using a drug that has an enteric coating, fat absorption is on average 20% higher than when using a conventional drug in the same dose. However, in patients with chronic pancreatitis, the production of bicarbonates is significantly reduced, which leads to impaired alkalization in the duodenum and impaired activation of accepted enzymes. In this case, the effectiveness of the encapsulated enzymes may be significantly reduced.

Rice. 3. Effect of a microtablet drug with an enteric coating

The downside of enteric-coated drugs is that the enzymes do not have time to activate in the duodenum, the main site of production of pancreatic regulatory peptides. The low activity of proteases in the duodenum does not allow interrupting the stimulation of pancreatic secretion through a negative feedback mechanism and does not reduce the pressure in the ducts and parenchyma of the pancreas. High intrapancreatic pressure is considered the main mechanism for the development of intense pain in chronic pancreatitis, and therefore encapsulated enzymes are recommended only as replacement therapy, and for pain relief (especially with intraductal hypertension) - traditional pancreatin tablets or powder.

However, according to our own data, treatment of chronic pancreatitis using encapsulated pancreatin

led to a significant decrease in the intensity of abdominal pain in the examined patients (p=0.0063; Fig. 4). Moreover, the degree of pain reduction significantly depended on the degree of decrease in fecal elastase activity compared to the initial level (p = 0.0219). Thus, the analgesic effect of the therapy directly depended on the degree of suppression of the exocrine function of the pancreas in the patient. The exocrine function of the pancreas according to the elastase test (determination of fecal elastase using an immunoreactive method) significantly decreased compared to the background: 279.46±27.41 μg/g and 254.87±26.74 μg/g (n=52, p= 0.0152).

Rice.
4. Intensity of pain before treatment and while taking KPMES. The particle size of microgranulated preparations should not exceed 2 mm
, which ensures simultaneous evacuation of food and enzymes from the stomach. Further reduction in granule size does not lead to an increase in the efficiency of food digestion [13]. The administration of pancreatin capsules in a dose of 16–18 thousand units per meal to patients with chronic pancreatitis after surgical interventions on the pancreas (pancreaticoduodenectomy and drainage of the Wirsung's duct) for 2.5 years made it possible to reduce the loss of fat in feces from 33.6 g/day to 15.3 g/day [7]. There was a statistically significant increase in the body weight of patients and biochemical indicators of trophological status (serum iron, total iron-binding capacity of blood serum, total number of lymphocytes).

According to information obtained by Farkas G., Takacs T. et al. (1999), prescribing microgranulated pancreatin to patients after surgery on the pancreas at a dose of 25 thousand units. 3 times a day for 10 days did not lead to changes in pancreatic function compared to placebo [12]. Nevertheless, the therapy made it possible to effectively eliminate the symptoms of maldigestion, stabilize body weight (in the comparison group - weight loss of 3.5 kg over the same time) and increase the breakdown of carbohydrates by 35%.

Adequate therapy of exocrine pancreatic insufficiency syndrome requires the use of high doses of enzyme preparations. It is usually necessary to use enzymes in encapsulated form. The drug dosage regimen is as follows: 1–4 capsules of the enzyme preparation with main meals (at the beginning of a meal) and 1 capsule (tablet) with a small amount of food. The patient should avoid eating foods rich in fiber, as they reduce enzyme activity as in vitro

, and
in vivo
. The main component of the enzyme preparation, which determines the effectiveness of the treatment of digestive disorders, is lipase. At the same time, proteases and, above all, trypsin are the main inhibitors of lipase. Therefore, to relieve steatorrhea, one should not strive to significantly increase the proteolytic activity of chyme. Often, a high dose of enzymes entering the stomach does not provide the desired result: the main components of enzyme preparations, lipase and trypsin, quickly lose activity in an acidic environment. Therefore, the effectiveness of enzyme therapy can be increased by the simultaneous administration of antacid or antisecretory drugs, but it must be remembered that antacids containing calcium or magnesium weaken the effect of enzyme drugs.

Many open questions remain in assessing the effectiveness of enzyme replacement therapy, in particular, replacement therapy, and determining optimal doses. Thus, there are two groups of patients: patients in whom pancreatic secretion exceeds 10%, but nevertheless have steatorrhea; and those in which lipase secretion is practically absent, but normal digestion and absorption of fat is maintained. This may be due, respectively, to the different reserve secretory capacity of the pancreas and to the action of non-pancreatic lipases (produced by the mucous membrane of the tongue and stomach, mainly the upper part of the greater curvature). Researchers estimate that patients with exocrine pancreatic insufficiency may absorb more than 50% of dietary fat in the absence of detectable pancreatic lipase activity. It has been shown that in patients with severe pancreatitis with steatorrhea, when taking 100 g of fat with food, 20–50 g of fat can be absorbed without enzyme replacement therapy. According to Abrams CK, Hamosh M. et al. (1987) [5], in patients with pancreatic exocrine insufficiency, non-pancreatic lipases provide more than 90% of the total lipolytic activity at the level of the duodenojejunal junction, whereas in healthy people - 7%. This observation may, at least in part, explain why some patients do not require enzyme replacement therapy after total pancreatectomy.

However, in a double-blind crossover study, Neoptolemos JP, Ghaneh P. et al. (1999) in 37 patients with CP with exocrine insufficiency after extensive resection of the pancreas, there were no significant differences in stool frequency, fecal volume and daily loss of fat in feces while taking a standard or high dose of pancreatin. In this regard, the authors conclude that the main advantage of modern drugs with a high content of pancreatin in one capsule is convenience for the patient, which ensures more accurate adherence to the treatment regimen. In another study, when prescribing a capsulated drug to patients with chronic pancreatitis, no dependence of fecal fat content on the dose of the drug was found [15], which suggests the presence of a certain threshold of enzyme efficiency, upon reaching which a further increase in dose does not lead to a decrease in steatorrhea.

Treatment of patients with disorders of motor function and colon tone

, for example, with irritable bowel syndrome, in addition to antispasmodics, enveloping, psychotropic drugs, sometimes requires the use of digestive enzymes. The use of enzymes, which contain bile components, causes increased intestinal motility and helps resolve constipation in patients. Enzyme preparations that contain hemicellulase (Digestal) improve the digestion of plant foods and reduce bloating, which gives a good symptomatic effect.

Healthy individuals can take digestive enzymes to relieve dyspeptic symptoms after overeating

. Occasional intake of small doses of digestive enzymes (1-2 tablets) does not affect pancreatic function and is considered safe. In this situation, drugs with bile components have proven themselves to be the best.

The reasons for the ineffectiveness of replacement therapy may be associated with both inaccurate diagnosis of the disease and inadequate therapy. Sometimes a lower dose of the drug is prescribed to reduce the cost of treatment. Patients may incorrectly follow the prescribed treatment regimen: reduce the frequency of doses or take the enzyme at the wrong time (before or after meals). Enzyme preparations are ineffective for steatorrhea of ​​extrapancreatic origin (celiac disease, giardiasis, etc.). The action of enzymes is impaired in intestinal motility disorders. Incorrect treatment regimen: prescription of enzymes that do not have an acid-protective shell without inhibitors of gastric secretion; the use of drugs that, due to the large size of the granules, do not enter the duodenum simultaneously with food.

Side effects of enzyme therapy are usually not severe. The most dangerous of them, the development of fibrosing colopathy, occurs in children with cystic fibrosis with long-term intake of very high doses of encapsulated enzymes - more than 50 thousand units of lipolytic activity per 1 kg of body weight per day. In addition, patients may experience pain in the oral cavity (usually when taking enzymes in powder form), skin irritation in the perianal area, and a feeling of discomfort in the abdomen. Long-term enzyme therapy in high doses can cause hyperuricemia, in some cases allergic reactions to pork protein occur (including in relatives of patients with exocrine pancreatic insufficiency and medical personnel). The formation of complexes with enzymes sometimes leads to impaired absorption of folic acid.

The list of references can be found on the website https://www.rmj.ru

Enzyme preparation –

Digestal (trade name)

(ICN Pharmaceuticals)
Literature:
1. Geller L. I., Pashko M. M., Obukhova G. G. Exocrine and endocrine pancreatic disorders in chronic pancreatitis. // Sov. Honey. – 1989. – No. 8. – pp. 4–7.

2. Yakovenko E.P. Enzyme preparations in clinical practice // Klin. pharm. and ter., 1998, No. 1, p. 17–20.

3. A primer of pancreatitis PGLankisch, M.Buchler, J.Mossner, S.Muller–Lissner // Springer, 1997.

4. Abrams CK, Hamosh M., Lee TC, Ansher AF, Collen MJ, Lewis JH, Benjamin SB, Hamosh P. Gastric lipase: localization in the human stomach. // Gastroenterol. – 1988. – Vol. 95. – P. 1460–1464.

5. Abrams CK, Hamosh M, Dutta SK, Hubbard VS, Hamosh P. Role of nonpancreatic lipolytic activity in exocrine pancreatic insufficiency. // Gastroenterol. – 1987. –Vol. 92. – P. 125–129.

6. Banks PA Acute and chronic pancreatitis. In: Sleisenger and Fordtran's gastrointestinal and liver disease: pathophysiology/diagnosis/management / Mark Feldman, Bruce F. Scharschmidt, Marvin H. Sleisenger–6th ed. WBSaunders company, 1998.

7. Braga M., Cristallo M., De Franchis R., Mangiagalli A., Agape D., Primignani M., Di Carlo V. Correction of malnutrition and maldigestion with enzyme supplementation in patients with surgical suppression of exocrine pancreatic function. // Surg. Gynecol. Obstet. – 1988. – Vol. 167, Dec. – No. 6. – P. 485–492.

8. Creutzfeldt W., Kern E., Kummerle F., Schumacher J. Die radikale Entfernung der Bauch–speicheldruse beim Menschen – Indikationen, Ergebnisse, Folgeerscheinungen. // In: Heilmeyer L, Schoen R, de Rudder B (eds) Ergebnisse der Inneren Medizin. – Springer, Berlin-Gottin-gen-Heidelberg. – 1961. – Vol. 16. – P. 79–124.

9. DiMagno EP Future aspects of enzyme replacement therapy. In Lankisch (Ed.) Pancreatic enzymes in health and disease, pp. 209–214, Springer–Verlag, Berlin, Heidelberg, 1991.

10. DiMagno EP Patterns of human exocrine pancreatic secretion and fate of human pancreatic enzymes during aboral transit. In Lankisch (Ed.) Pacreatic enzymes in health and disease, pp. 1–10, Springer–Verlag, Berlin, Heidelberg, 1991.

11. Diseases of the gut and pancreas. JJMisiewicz, REPounder, CWVenables eds., Blackwell scientific publication, 1994, vol. 1.

12. Farkas G., Takacs T., Baradnay G., Szasz Z. Effect of pancreatin replacement on pancreatic function in the postoperative period after pancreatic surgery. // Orv. Hetil. – 1999. – Dec 5. – vol. 140. – No. 49. – P. 2751–2754.

13. Halm U., Loser C., Lohr M., Katschinski M., Mossner J. A double-blind, randomized, multicentre, crossover study to prove equivalence of pancreatin minimicrospheres versus microspheres in exocrine pancreatic insufficiency. // Aliment. Pharmacol. Ther. – 1999 – Vol. 13. – No. 7. – P. 951–957.

14. Lankisch PG, Banks PA Pancreatitis. Springer-Verlag: Berlin, Heidelberg. – 1998. – P. 377.

15. Opekun AR Jr, Sutton FM Jr, Graham DY Lack of dose–response with Pancrease MT for the treatment of exocrine pancreatic insufficiency in adults. // Aliment. Pharmacol. Ther. – 1997, Oct. – Vol. 11. – No. 5. – P. 981–986.

16. Paris JC A Multicentre Double–Blind Placebo–Controlled Study of the Effect of a Pancreatic Enzyme Formulation (Panzytrat(r) 25,000) on Impaired Lipid In Adults with Chronic Pancreatitis //Drug Invest. 5(4):229–237, 1993.

17. Riley SA, Marsh MN Maldigestion and malabsorption. In: Sleisenger and Fordtran's gastrointestinal and liver disease: pathophysiology/diagnosis/management / Mark Feldman, Bruce F. Scharschmidt, Marvin H. Sleisenger–6th ed. WBSaunders company, 1998.

18. Roberts IM Enzyme therapy for malabsorption in exocrine pancreatic insufficiency. Pancreas 1989, #4, 496–503.

19. Sarles H., Pastor J., Pauli AM, Barthelemy M. Determination of pancreatic function. A statistical analysis conducted in normal subjects and in patients with proven chronic pancreatitis (duodenal intubation, glucose tolerance test, determination of fat content in the stools, sweat test). //.Gastroenterol. – 1963. – Vol. 99. – P. 279–300.

20. Stead RJ, Skypala I., Hodson ME Treatment of steatorrhoea in cystic fibrosis: a comparison of enteric–coated microspheres of pancreatin versus non–enteric–coated pancreatin and adjuvant cimetidine. // Aliment. Pharmacol. Ther. – 1988, Dec. – Vol. 2. – No. 6. – P. 471–482.

The best enzymes for digestion

How does pancreatic insufficiency manifest?

People with pancreatic enzyme deficiency develop digestive insufficiency. They cannot digest proteins, fats and carbohydrates fully. As a result, for example, the phenomenon of creatorrhoea and steatorrhea occurs. In the first case, undigested muscle fibers can be found in the feces after eating meat, and in the second, neutral, undigested fat exists in the feces due to a lack of pancreatic lipase.

As a result, complaints arise about instability of digestion, bloating, intolerance to certain types of food, alternating constipation and diarrhea. This leads to chronic damage to the intestines - secondary dysbiosis and vitamin deficiency develop (after all, many vitamins are produced by microbes living inside us), and immunity decreases. It is for the correction of these disorders that enzymatic preparations are intended.

Principles of treatment

Depending on the cause and course of exocrine pancreatic insufficiency (absolute, long-term or relatively short-term), treatment can be episodic or long-term.

In case of irreversible pancreatic insufficiency, enzyme preparations must be used for a long time, even throughout life, but their dose varies depending on the amount and nature of food eaten, the functional state of the digestive organs, and concomitant diseases.

Treatment consists of two stages: diet and pancreatin replacement therapy.

Recommendations for prescribing enzyme preparations for syndromes of impaired digestion and absorption

Digestion is a process that ensures the replenishment of the body’s energy and plastic resources through the processing of various food substrates entering the digestive tract. First of all, the digestive glands take part in its implementation, the secretion of which contains enzymes (Table 1).

Disorders of the digestive processes (maldigestion) and absorption (malabsorption) are the most common syndromes in the practice of a general practitioner and gastroenterologist. Their development may be due to insufficient production of digestive enzymes or a decrease in their activity. The mechanisms of disturbances in the processes of digestion and absorption are diverse and are determined primarily by the diseases underlying them (Table 2).

Clinical manifestations of maldigestion and malabsorption syndromes also depend on the mechanisms of their development (Table 3).

With maldigestion and malabsorption syndromes, specific syndromes often develop due to a deficiency of certain vitamins and microelements in the body. For example, deficiency of retinol (vitamin A) is accompanied by the development of hemeralopia (night blindness), xerophthalmia, keratomalacia, hyperkeratosis; deficiency of nicotinamide (vitamin PP) - dermatitis, diarrhea, dementia and weight loss; deficiency of cyanocobalamin (vitamin B12) - painful neuropathy, ataxia, parasthesia, impaired temperature sensitivity, macrocytic anemia; deficiency of ascorbic acid (vitamin C) - hemorrhages under the periosteum and at the base of the hair follicles; iron deficiency - muscle weakness, glossitis, colonychia, microcytic anemia, etc. The main direction in the treatment of patients with syndromes of impaired digestion and absorption, especially when it is impossible to eliminate the causes of their development, is enzyme replacement therapy, sometimes vitamins and microelements.

Currently, the doctor has a large number of enzyme preparations at his disposal, differing in the number of incoming components, the degree of enzyme activity, production methods and release forms. All enzymes can be divided into two groups: pancreatin in its pure form and pancreatin + bile components + hemicellulase. Pancreatin contains three enzymes: lipase, protease and amylase. The drug is considered effective if 1 g of pancreatin contains about 40,000 units of lipase (International Pharmaceutical Federation unit). Lipase is involved in the hydrolysis of neutral fat emulsified by bile, mainly in the duodenum, since when lipase enters the jejunum, its activity decreases sharply. Proteases in pancreatin mainly consist of trypsin, under its influence proteins, mainly of animal origin, are broken down into amino acids; in addition, trypsin is involved in the regulation of pancreatic secretion via a feedback principle. Amylase breaks down extracellular polysaccharides (starch, glycogen) and practically does not participate in the hydrolysis of plant fiber. Pancreatin preparations do not affect the function of the stomach, liver, motility of the biliary system and intestines, but reduce the secretion of pancreatic juice.

A number of modern enzyme preparations, along with pancreatin, include bile acids (bile) and hemicellulase. Preparations containing bile acids increase pancreatic secretion and choleresis, stimulate intestinal and gallbladder motility. Bile acids increase the osmotic pressure of intestinal contents, and under conditions of microbial contamination of the intestine, their deconjugation occurs with the subsequent development of osmotic and secretory diarrhea. Bile acids enter the enterohepatic circulation and are metabolized in the liver, which increases its functional load. Deconjugated bile acids damage the gastrointestinal mucosa.

Enzyme preparations containing bile acids should not be prescribed for acute and chronic pancreatitis, hepatitis and cirrhosis of the liver, diarrhea, peptic ulcers and inflammatory bowel diseases.

The presence of hemicellulase in the enzyme preparation ensures the breakdown of polysaccharides of plant origin.

When prescribing a particular enzyme preparation, it is necessary first of all to take into account its composition.

The second factor determining the activity of treatment is the form of release of the drug. Most enzyme preparations are available in the form of dragees or tablets with a diameter of 5 (or more) mm in enteric coatings, which protects enzymes from release in the stomach and destruction by hydrochloric acid of gastric juice. Solid particles with a diameter of no more than 2 mm can be evacuated from the stomach along with food into the duodenum. Larger particles, in particular enzyme preparations in tablets or dragees, are evacuated during the interdigestive period, when food chyme has already left the duodenum. As a result, the drugs do not mix with food and do not participate in digestion. To ensure quick and “homogeneous” mixing with food chyme, highly active multienzyme preparations were created in the form of microtablets (pancintrat) and microspheres (Creon), the diameter of which does not exceed 2 mm. The drugs are enclosed in a gelatin capsule, which is destroyed in the stomach; the contents (microtablets and microspheres) are mixed with food chyme and, along with it, gradually enter the duodenum. When the pH of the duodenal contents is above 5.5, the shells of microspheres and microtablets dissolve and enzymes begin to act on a large surface, similar to the physiological processes of digestion.

The third factor determining the activity of enzyme preparations is the intraduodenal pH level and effective duodenal motility, which ensures long-term contact of enzymes with food chyme. If the pH of the duodenal contents decreases to 3.5 and below, then irreversible inactivation of lipase and trypsin and precipitation of bile acids occur, leading to impaired emulsification and absorption of fats. The main reasons for a drop in pH in the duodenum are bacterial overgrowth in the intestine, hyperacidosis, and decreased bicarbonate secretion. To increase the pH in the duodenum, histamine H2 receptor blockers (ranitidine, famotidine), sometimes proton pump blockers (omeprazole, etc.), antacid drugs (Maalox, Gastal, etc.) are used, and the duodenum is necessarily decontaminated with antibacterial drugs (Biseptol, etc. .), and sometimes antiparasitic (metronidazole, etc.) agents.

Doses of drugs and duration of treatment are determined individually, depending on the leading mechanism of this disorder. The effectiveness of enzyme preparations can sometimes depend on motor disorders of the upper digestive tract. To eliminate these disorders, prokinetics such as Motilium are most often used (10 mg 15 minutes before meals three to four times a day).

The most important factor determining the success of therapy is the correct choice of enzyme preparation, its dose and duration of treatment. When choosing a drug, the nature of the disease and the mechanisms underlying digestive disorders are taken into account (Table 5).

The main disadvantage of enzyme therapy is that its activity sometimes depends on other pathogenetic mechanisms. The effect of therapy with enzyme preparations can be increased by eliminating the syndrome of excessive microbial contamination of the duodenum and other parts of the small intestine by conducting courses of antimicrobial therapy, and in case of acidification of the duodenum - by restoring the desired pH using histamine H2 receptor blockers and antacids (Maalox, etc.) .

Magazine for pharmacy business professionals

The summer picnic season is accompanied by an increase in demand for drugs that improve digestion. Let's remember the features of the products that support the pancreas in difficult times.

Potential consumers of enzymatic drugs are plagued by doubts about the capabilities of their digestive system. He heard about the existence of drugs that can increase the “safety margin” of the pancreas, and asks the chief captain to recommend such a remedy. And at this stage tricky questions may arise.

What active ingredients are included in modern enzymes?

Today two groups of enzyme preparations are produced: pancreatin

in pure form and in combination with
bile components
and
hemicellulase
. Pancreatin is obtained from the pancreas of pigs and cattle. It contains three enzymes: lipase, protease and amylase, which break down fats, proteins and extracellular carbohydrates (starch).

Pancreatin is considered a classic enzyme preparation, corresponding in composition to an extract of pancreatic juice.1

What is the difference between pancreatin preparations and combined enzymes?

Pancreatin compensates for enzyme deficiency of the pancreas without affecting the function of the stomach, liver, biliary system and intestines. But it reduces the secretion of pancreatic juice, providing the organ with a “rest period” and reducing pain.

Combination drugs work a little differently. The pancreatin they contain covers enzyme deficiency, bile acids stimulate the pancreas, intestinal and gallbladder motility, and hemicellulase breaks down polysaccharides of plant origin.

A lipid-rich dinner or lunch can be “seasoned” with 20–75 thousand units of lipase, and 5–25 thousand units are enough to successfully digest a light snack1.

Does the release form affect the effectiveness of enzyme preparations and if so, how?

The release form is a factor that largely determines the result of enzyme treatment. For a drug to work effectively, it must travel from the stomach to the intestines along with the bolus of food. But only solid particles with a diameter of less than 2 mm, the so-called microspheres or microtablets with pancreatin, are capable of such a feat. They are enclosed in a gelatin capsule, which is destroyed in the stomach to release the active substance. The “miniature” diameter of the particles allows them to mix with the food bolus, successfully penetrate the intestines and develop their full healing power.

What dose of enzymes should be recommended before a festive feast?

For a healthy person, the dose of enzyme preparations is selected based on the fat content of food. In addition, it is important to remind the buyer of the rule for taking such drugs: they should be taken immediately before or during meals.

When are enzyme preparations contraindicated?

All enzymes are prohibited in case of acute or exacerbation of chronic inflammation of the pancreas. Preparations containing bile components are also contraindicated for diseases of the liver and biliary tract.

DO YOU KNOW THAT…

• Enzyme preparations not only perform a replacement function, compensating for the deficiency of their own enzymes, but also suppress the production of pancreatic juice. As a result, the pressure in the pancreatic ducts decreases, and the pain syndrome that occurs against the background of inflammatory processes in the pancreas decreases or completely stops. As a rule, for analgesic purposes, enzymes are prescribed in high doses before meals for several weeks2.
• For outstanding discoveries in the field of biochemistry, which paved the way for the creation of enzyme preparations, American scientists James Sumner, John Northrop and Wendell Stanley received the Nobel Prize in 1946.
• To digest 500 g of high-calorie food, the body requires at least 30–35 thousand units of lipase.3

_______________________________________________________________________________________________________________________________________________________________________

1. Shulpekova Yu.O., Ivashkin V.T. Correction of digestive disorders with pancreatic enzyme preparations // Russian Medical Journal. Diseases of the digestive system. – 2005. – T. 7. – No. 1. – pp. 13-17.

2. Silivonchik N.N., Kalashnikov N.A. Scientific achievements - in the practice of a gastroenterologist // Health of Ukraine. – 2007. – 9. – P. – 2007. – P. 58-59. 3. Shukanov K. On the effectiveness and characteristics of enzyme preparations in the treatment of diseases of the gastrointestinal tract // Khabarshysy. – P.152.

Marina Pozdeeva

Magazine "Russian Pharmacies" No. 9-10, 2016

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