Effective drugs for pancreatitis: treatment regimens

One of the components of complex treatment of inflammation of the pancreas is drug therapy, and timely use of effective drugs for pancreatitis plays a key role in stopping the pathological process and maintaining the functions of the entire gastroentero-pancreatic endocrine system.

Since acute and chronic pancreatitis have some etiological and morphological differences, and their clinical manifestations can change depending on the degree of impairment of the secretory functions of the gland, there are certain problems with the choice of the correct treatment tactics and the use of pharmacological agents.

Treatment of pancreatitis with medications

It should be borne in mind that acute pancreatitis is an urgent condition, and its treatment is carried out only in a clinical hospital, where patients, in most cases, are urgently hospitalized by an ambulance team. In severe cases, which occur in 20-25% of patients, a condition close to abdominal pain shock may be observed, and with a sharp loss of fluid due to vomiting - and hypovolemia.

Therefore, medications for acute pancreatitis should first of all relieve acute pain accompanied by nausea, vomiting, increased heart rate and a drop in blood pressure, and also restore the water-electrolyte balance in the body. Pain is relieved by parenteral administration of analgesics (Novocaine with glucose, Analgin, Ketanov) or antispasmodics: No-shpa, Papaverine hydrochloride, Platyphylline hydroartate, Metacin or Ganglefen hydrochloride.

At the same time, fluid is restored and hemodynamics are stabilized: a drip is repeatedly administered for pancreatitis - with saline, glucose and other components that support the work of various systems and organs. Systemic inflammatory response syndrome, sepsis and multiple organ failure develop in patients with severe acute pancreatitis due to the fact that activated pancreatic enzymes digest the membranes of its own cells.

Therefore, intensive care measures are combined with the prevention of infection of the affected tissues of the pancreas or the fight against an existing bacterial infection, and antibiotics are used in gastroenterology to solve this problem (most often, these are Amoxiclav or third-generation cephalosporins). For the specifics of their use in pediatric gastroenterology, see - Acute pancreatitis in children

Another task is to suppress the secretory functions of the gland, not only to limit its load as much as possible, but also to stop the irreversible destruction of cells leading to pancreatic necrosis. For this purpose, there are drugs that inhibit the synthesis of pancreatic enzymes. Their main names are:

• Aprotinin (synonyms: Contrycal, Gordox, Trascolan);
• Octreotide (Octride, Octretex, Sandostatin, Seraxtal).

As a rule, they are used only for acute pancreatitis in adults. More about them below.

Medicines for chronic pancreatitis

The most important point that the treatment regimen for pancreatitis with drugs includes is to slow down the functional activity of the pancreas, that is, to reduce the production of its enzymes. It is generally recognized that the parenchyma cells of the gland are damaged by the proteases it synthesizes, and the damage is initiated in the acinar cells after premature intracellular activation of digestive enzymes.

In the chronic form of the disease, Pirenzepine (Gastrozepin) or Prifinia bromide (Riabal) can be used to reduce the production of proteolytic enzymes. These drugs are also prescribed for exacerbation of pancreatitis: if the patient is hospitalized, Pirenzepine is used parenterally.

A deficiency of digestive pancreatic enzymes is associated with chronic inflammation and damage to the secretory cells of the pancreas. To cover it, gastroenterologists prescribe enzyme preparations containing proteases (breaking down proteins), amylase (for hydrolyzing complex carbohydrates) and lipase (so that the body can absorb fats). These include Pancreatin, which has many trade names: Pancitrate, Pangrol, Pancreazim, Penzital, Mikrazim, Creon, Mezim, Gastenorm forte, Vestal, Ermital, etc. In addition to pancreatitis, indications for the use of enzymes include problems with the digestive system of various etiologies, dyspepsia, flatulence, cystic fibrosis, and nutritional errors.

In order to suppress the production of hydrochloric acid in the stomach, the increased production of which also activates the synthesis of pancreatic juice, drugs from three more pharmacological groups are introduced into the treatment regimen for chronic pancreatitis:

• antisecretory H2-antihistamines: Ranitidine (Ranigast, Aciloc, Zantac, etc.) or Famotidine (Pepcidin, Quamatel, Gastrosidin);
• inhibitors of the hydrogen-potassium ATPase enzyme (proton pump): Omeprazole (Omez, Gastrozol, Promez), Rabeprazole or Lansoprol (Lanzol, Clatinol, etc.);
• antacids with aluminum and magnesium hydroxides - Almagel (Alumag, Gastracid, Maalox), which neutralize acid in the stomach.

The mechanism of action, release form, method of administration and dosage and other pharmacological characteristics of the drugs of these three groups are described in detail in the material - Tablets for stomach ulcers

Read about what medications are needed for pancreatitis in children and the specifics of their use in childhood in the publication - Treatment of chronic pancreatitis

And medications for pancreatitis that inhibit the production of pancreatic enzymes (Aprotinin, Octreotide, Pirenzepine, Prifinium bromide) and replenish their deficiency that occurs subsequently (Pancreatin) are discussed in detail below.

Release form

The anti-enzyme agent Aprotinin is available in the form of an injection solution (in 10 ml ampoules) and powder for its preparation (in vials of various capacities, which come with an isotonic NaCl solution).

The release form of Contrikal is a lyophilisate in ampoules (2 ml) for the preparation of a solution (a solvent is also included). And Gordox and Trascolan are ready-made injection solutions (in ampoules of 10 ml).

The drug Octreotide (Sandostatin) is available as a solution for infusions and subcutaneous injections (in 1 ml ampoules or 5 ml vials); Seraxtal is available in disposable syringes.

Pirenzepine (Gastrozepin) can be available in the form of a solution for parenteral administration (in 2 ml ampoules) or in the form of tablets (25 mg).

Prifinia bromide is a solution for oral administration (50 ml bottles), and Riabal also comes in the form of a syrup (60 ml bottles).

Pancreatin is a tablet, but some of its generics are in capsule or pill form.

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Pharmacodynamics

The proteolytic enzyme inhibitor Aprotinin (and other synonymous drugs) neutralizes their activity, including trypsin and chymotrypsin synthesized by the pancreas, which, in pancreatitis, interact with the extracellular matrix of the gland parenchyma, causing irreversible fibrosis of its structures.

Octreotide is a synthesized analogue of the endogenous peptide hormone somatostatin (produced by the pancreas and hypothalamus), and its pharmacodynamics are based on the function of this hormone - suppression of somatotropic hormone; gastric enzyme gastrin; enterokinase, secretin and cholecystokinin of the small intestine, as well as protease proenzymes of the pancreas (trypsinogen and chymotrypsinogen, kallikreinogen, etc.). This occurs due to the binding of Octreotide to somatostatin receptors (SRIF) of the pancreas, localized in its exocrine part.

The pharmacological action of the anticholinergic drugs Pirenzepine (a benzodiazepine derivative) and Prifinium bromide is a selective effect on acetylcholine receptors, which leads to blocking their excitation and parasympathetic innervation of the glands of the digestive system, which includes the pancreas. As a result, not only the production of pancreatic enzymes is reduced, but also the synthesis of hydrochloric acid, pepsin and chymosin in the stomach.

The result of inflammation of the pancreas is its partial or complete secretory dysfunction, which makes normal digestion of food impossible. It is to ensure digestion that I use such drugs for chronic pancreatitis as Pancreatin, which contains enzymes from the pancreas of pigs and cows (protease, amylase and lipase), replacing the endogenous components of pancreatic juice.

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Pharmacokinetics

The polypeptide substance aprotinin (the active component of Aprotinin, Contrycal and Gordox) after entering the systemic bloodstream reaches the tissues and remains in their extracellular matrix, mostly in the gastrointestinal tract and liver. It is completely eliminated from the blood plasma on average five hours after administration. Biotransformation of part of the drug occurs in the liver, but its main place of metabolism is the kidneys, from where it is excreted with urine in about 48 hours.

Pharmacokinetics Octreotide is characterized by rapid absorption with the maximum plasma level reached half an hour after subcutaneous administration of the drug, and the binding of octreotide acetate to blood proteins reaches 65%. Just as quickly - within 1.5 hours - half of the administered dose is excreted from the body. Two-thirds of the drug is eliminated by the intestine (with feces), the rest in its original form is excreted in the urine.

Absorption of Pirenzepine does not exceed 50%, and the highest level of the active substance in the blood plasma is observed after 120 minutes. Metabolism occurs with the help of liver enzymes, half of the drug is not subject to breakdown; metabolites are excreted through the kidneys and intestines.

Pancreatin enzymes are released at the beginning of the small intestine, ensuring the digestive process and the breakdown of proteins, carbohydrates and fats consumed with food. The enzymes begin to act approximately half an hour after taking the drug.

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Dosing and administration

Aprotinin is administered intravenously; the dose is calculated individually. Most often, an IV drip for acute pancreatitis is administered at a dosage of 300,000–500,000 IU/day with a gradual reduction over 10–15 days. The maximum daily dose for children is 14,000 IU per kilogram of body weight.

The method of administration of Octreotide is also parenteral, but it is administered subcutaneously: 0.1-0.25 mg three times a day.

Pirenzepine in solution is used by injection, in tablets - taken orally half an hour before meals: adults - 50 mg (two tablets) twice a day; children over six years old - one tablet three times a day.

The daily dose of Prifinium bromide solution is determined by body weight: 1 mg per kilogram; the resulting amount is divided into three doses over 24 hours.

During an exacerbation of pancreatitis (after consultation with a gastroenterologist), these medications can be taken in increased dosages.

And the dosage of Pancreatin taken orally during meals is calculated by the attending physician based on the level of pancreatic enzyme deficiency in a particular patient. For adults, the daily dose can range from 50,000 to 150,000 U (for lipase). The maximum permissible dose (if the pancreas does not produce enzymes at all) is 400,000 U/day.

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Use pancreatitis meds during pregnancy

According to the instructions for the specified drugs, use during pregnancy

Aprotinin is prohibited in the first and third trimesters, and during the second trimester it is allowed only in case of a threat to the patient's life.

Octreotide is contraindicated during pregnancy and lactation.

The use of Pirenzepine and Prifinium bromide is prohibited during the first three months of pregnancy; after that, it is allowed if the results of their use outweigh the possible negative consequences for the development of the fetus.

For more details see – Pancreatin during pregnancy

Contraindications

The medications under consideration for pancreatitis have the following contraindications for use:

Aprotinin - blood clotting disorder, breastfeeding period.

Octreotide - patients under 18 years of age.

Pirenzepine and Prifinium bromide - high intraocular pressure and history of glaucoma, prostate enlargement of any etiology, cholecystitis and/or cholelithiasis, kidney stones, acute dysuria, decreased intestinal peristalsis and inflammation of the colon.

Pancreatin – acute pancreatitis, exacerbation of chronic pancreatitis, early childhood.

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Side effects pancreatitis meds

The use of Aprotinin may cause nausea and vomiting, the appearance of a blood clot at the injection site; vascular hypotension and heart rate disturbances; muscle pain; allergy with inflammation of the conjunctiva, nasal mucosa and bronchial spasm; impaired consciousness (up to the appearance of hallucinations and psychosis).

The main side effects of Octreotide are headache and dizziness; deterioration of liver function and increased bilirubin levels in the blood; hyper- or hypoglycemia; decreased thyroid-stimulating hormones; allergic reactions. With prolonged use of Octreotide, there is a risk of developing gallstone disease.

Possible side effects of treatment with Pirenzepine or Prifinium bromide include: urticaria, dry mucous membranes of the oropharynx, nausea, deterioration of bowel function, arterial hypertension, increased intraocular pressure, dilated pupils and decreased vision.

Since Pancreatin is taken for a long time in case of chronic dysfunction of the pancreas, allergies and problems with the gastrointestinal tract may occur. In addition, side effects of enzyme preparations may manifest themselves as an increase in the content of uric acid in the urine (hyperuricosuria) and in the blood (hyperuricemia).

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Overdose

If the dose of Pirenzepine is exceeded, dizziness, increased heart rate, decreased blood pressure and general weakness occur. It is necessary to wash out the stomach and take a laxative. A significant overdose can cause a serious psychotic disorder and respiratory depression. In such cases, artificial ventilation of the lungs may be required.

Pancreatin overdose produces more pronounced side effects, especially concerning bowel function and retention of uric acid salts in the kidneys and blood plasma.

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Interactions with other drugs

According to the official instructions, the protease inhibitor Aprotinin is characterized by almost complete incompatibility with any other medications.

Pirenzepine and Prifinium bromide potentiate the action of opioid analgesics, m-anticholinergics, neuroleptics, and drugs for the treatment of Parkinson's disease (in particular, dopamine agonists and anticholinergics).

It is necessary to take into account interactions with other Pancreatin preparations, which: reduces iron absorption; inactivates many antacids; reduces the therapeutic effect of acetylsalicylic acid and enhances the effect of m-anticholinergics.

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What medications should not be taken for pancreatitis?

The following medications are contraindicated for chronic pancreatitis:

• alcohol tinctures;
• systemic antibiotics of the penicillin, tetracycline, and fluoroquinolone groups;
• sulfonamides (sulfadimezine, sulfazoline, etc.);
• diuretics (loop, thiazide and saluretics);
• Warfarin and other indirect anticoagulants;
• drugs containing trans-retinoic acid;
• valproic acid based products;
• glucocorticosteroids;
• adrenocorticotropic hormones
• any hormonal agents with estrogens;
• atypical neuroleptic drugs.

In addition, it should be borne in mind that in case of acute pancreatitis and exacerbation of chronic pancreatitis, one should not take drugs that replace pancreatic enzymes, that is, Pancreatin (and any of its synonyms).