Effective medications for pancreatitis: treatment regimens

One of the components of the complex treatment of inflammation of the pancreas is drug therapy, and timely effective medications for pancreatitis play a key role in stopping the pathological process and preserving the functions of the entire gastro-entero-pancreatic endocrine system.

Because acute and chronic pancreatitis have some etiological and morphological differences, and their clinical manifestations may vary depending on the degree of impairment of the secretory functions of the gland, there are certain problems with choosing the right therapeutic tactics and applying pharmacological agents.

Treatment of pancreatitis with medications

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

Therefore, drugs for acute pancreatitis, in the first place, should relieve acute pain, accompanied by nausea, vomiting, increased heart rate and blood pressure drop, and restore the water-electrolyte balance in the body. Pain is stopped by the parenteral administration of analgesics (Novocaine with glucose, Analgin, Ketanov) or antispasmodic drugs: No-shpi, Papaverina hydrochloride, Platifillin hydroartyrate, Metacin or Ganglefen hydrochloride.

At the same time, fluid recovery and hemodynamic stabilization are carried out: a dropper is often put on pancreatitis with saline, glucose and other components that support the work of various systems and organs. Syndrome of systemic inflammatory response, sepsis and multiple organ failure develop in severe acute pancreatitis in patients because activated pancreatic enzymes digest the membranes of its own cells.

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

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

• Aprotinin (synonyms - Contrikal, Gordoks, Traskolan);
• Octreotide (Octridium, Octretex, Sandostatin, Seraclast).

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

Medications for chronic pancreatitis

The most important item, which includes the scheme of treatment of pancreatitis with drugs, is to inhibit the functional activity of the pancreas, that is, to lower the production of its enzymes. It is generally recognized that the cells of the parenchyma of the gland are damaged by the proteases it synthesizes, and damage is initiated in acinar cells after premature intracellular activation of digestive enzymes.

In the chronic form of the disease, Pirenzepine (Gastrotsepin) or Prifinium bromide (Riabal) can be used to reduce the production of proteolytic enzymes. Also, these medications are prescribed for exacerbation of pancreatitis: if the patient is hospitalized - Pyrenzepine is used parenterally.

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

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

• antisecretory H2-antihistamines: Ranitidine (Ranigast, Acyloc, Zantac, etc.) or Famotidine (Pepsidine, Kwamatel, Gastrosidine);
• inhibitors of the enzyme hydrogen-potassium ATPase (proton pump): Omepraspal (Omez, Gastrozol, Primez), Rabeprazole or Lansoprol (Lanzol, Clatinol, etc.);
• antatsidy with hydroxides of aluminum and magnesium - Almagel (Alumag, Gastracid, Maaloks), neutralizing acid in the stomach.

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

About what medicines are needed for pancreatitis in children, and about the features of their use in childhood read in the publication -  Treatment of chronic pancreatitis

And the drugs for pancreatitis, which inhibit the production of pancreatic enzymes (aprotinin, Octreotide, Pirenzepine, Prinfonia bromide) and the deficiencies that fill them later (Pancreatin), are discussed in detail below.

Release form

Anti-enzyme agent Aprotinin is available in the form of a solution for injection (in ampoules of 10 ml) and powder for its preparation (in bottles of different capacity, to which an isotonic NaCl solution is applied).

Form of release Kontrikala - lyophilizate in ampoules (2 ml each) for solution preparation (solvent is also attached). A Gordoks and Traskolan - ready injection solutions (in ampoules of 10 ml).

The drug Octreotide (Sandostatin) has the form of a solution for infusions and subcutaneous injections (in ampoules of 1 ml or bottles of 5 ml); Seraclast - in disposable syringes.

Pirenzepine (Gastrotsepin) can be both in the form of a solution for parenteral administration (in ampoules of 2 ml), and in the form of tablets (25 mg each).

Prinfonia bromide - solution for oral administration (bottles of 50 ml), and Riabal also has the form of a syrup (60 ml bottles).

Pancreatin is a pill, but some of its generics are in the form of capsules or dragees.

[1], [2], [3], [4], [5], [6], [7]

Pharmacodynamics

Proteolitic enzyme inhibitor Aprotinin (and other drugs-synonyms) neutralizes their activity, including those synthesized by the pancreas of trypsin and chymotrypsin, which in pancreatitis interact with the extracellular matrix of the parenchyma of the gland, 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 is based on the function of this hormone - the inhibition of growth hormone; gastric enzyme gastrin; enterokinase, secretin and cholecystokinin of the small intestine, as well as protease proenzymes of the pancreas (trypsino- and chymotrypsinogens, kallikreinogen, etc.). This is due to the binding of Octreotide to the somatostatin receptors (SRIF) of the pancreas, localized in its exocrine part.

The pharmacological action of cholinolytics preparations of pyrenzepine (a benzodiazepine derivative) and Prinfonia bromide is a selective effect on the acetylcholine receptors, which leads to blocking their excitation and parasympathetic innervation of the glands of the digestive system, including 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 it impossible for normal digestion of food. It is to ensure digestion I use such drugs for chronic pancreatitis, like Pancreatin, containing pig pancreatic enzymes and cows (protease, amylase and lipase) that replace the endogenous components of pancreatic juice.

[8], [9], [10], [11], [12],

Pharmacokinetics

The polypeptide substance aprotinin (the active component of Aprotinin, Contrikal and Gordoks) after reaching the systemic circulation reaches the tissues and remains in their extracellular matrix, most of all in the digestive tract and liver. From plasma of blood it is completely deduced or removed on the average in five hours after introduction. Biotransformation of a part of the drug takes place in the liver, but the place of its main metabolism is the kidney, from which it is excreted in urine in about 48 hours.

The pharmacokinetics of Octreotide is characterized by rapid absorption with reaching the maximum plasma level in half an hour after the administration of the drug under the skin, 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 Pyrenzepine does not exceed 50%, and the highest level of active substance in blood plasma is observed after 120 minutes. Metabolism occurs with the help of liver enzymes, half of the drug does not decompose; metabolites are excreted through the kidneys and intestines.

Pancreatin enzymes are released at the beginning of the small intestine, providing the digestive process and the cleavage of proteins, carbohydrates and fats consumed with food. Enzymes begin to act about half an hour after taking the drug.

[13], [14], [15]

Dosing and administration

Aprotinin is administered intravenously; the dose is calculated individually. Most often, a dropper with pancreatitis in acute form is given in a dosage of 300,000-500,000 units / day. With a gradual decrease within 10-15 days. The maximum daily dose for children is 14,000 units per kilogram of body weight.

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

Pyrenzepine in solution is injected, in tablets - taken inside half an hour before meals: adults - 50 mg (two tablets) twice a day; children older than six years - one tablet three times a day.

Daily dose of the solution Prinfiya bromide is determined by the weight of the body: for each kilogram - 1 mg; the received amount is divided into three doses within 24 hours.

These medications with exacerbation of pancreatitis (after consulting a gastroenterologist) can be taken in a higher dosage.

A dosage of pancreatin taken orally during a meal is calculated by the attending physician in terms of the level of pancreatic enzyme deficiency in a particular patient. For adults, the daily dose can fluctuate in the range of 50000-150000 units (lipase). The maximum permissible dose (if the pancreas does not produce enzymes at all) is 400,000 units / day.

[26], [27], [28]

Use of the drugs in pancreatitis during pregnancy

According to the instructions to these drugs, use during pregnancy

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

Octreotide is contraindicated in pregnancy and during lactation.

Use of Pirenzepine and Prinfium bromide is prohibited in the first three months of pregnancy; further allowed if the results of their application outweigh the possible negative consequences for the development of the fetus.

For more details see -  Pancreatin in Pregnancy

Contraindications

Considered drugs in pancreatitis have the following contraindications for use:

Aprotinin - a violation of blood clotting, the period of breastfeeding.

Octreotide - the age of patients under 18 years of age.

Pirenzepine and Prifinia bromide - high intraocular pressure and glaucoma in the anamnesis, an increase in the prostate of any etiology, cholecystitis and / or cholelithiasis, kidney stones, dysuria in acute form, decreased intestinal peristalsis and inflammation of the large intestine.

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

[16], [17], [18], [19], [20], [21], [22]

Side effects of the drugs in pancreatitis

The use of aprotinin can cause nausea and vomiting, the appearance of a thrombus at the injection site; vascular hypotension and heart rate disorders; muscle pain; allergy with inflammation of the conjunctiva, nasal mucosa and bronchospasm; disorders of consciousness (before the appearance of hallucinations and psychosis).

The main side effects of Octreotide are expressed by headache and dizziness; deterioration of the liver and an increase in the level of bilirubin in the blood; hyper- or hypoglycemia; reduction of thyroid hormones; allergic reactions. With prolonged use of Octreotide, there is a threat of developing cholelithiasis.

Possible side effects of treatment with pirenzepine or Prinfium bromide include: urticaria, dryness of the mucous membranes of the oropharynx, nausea, worsening of the bowel, arterial hypertension, increased intraocular pressure, dilated pupils, and decreased vision.

Since Pancreatin is taken for a long time in chronic pancreatic dysfunction, allergy and gastrointestinal problems may occur. In addition, the side effects of enzyme preparations can be manifested by an increase in uric acid in the urine (hyperuricosuria) and in the blood (hyperuricemia).

[23], [24], [25]

Overdose

When the dose of Pyrenzepine exceeds the level of dizziness, rapidity of the pulse, a drop in blood pressure and general weakness. It is necessary to wash the stomach and take a laxative. A significant overdose can cause severe psychotic disorder and respiratory depression. In such cases, artificial ventilation may be required.

Pancreatin in overdose gives more pronounced side effects, especially concerning the work of the intestine and the retention of uric acid salts in the kidneys and blood plasma.

[29], [30], [31], [32], [33], [34]

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 Prifinia bromide potentiate the effects of opioid analgesics, m-holinoblokatorov, neuroleptics, as well as drugs for the treatment of Parkinson's disease (in particular, dopamine agonists and anticholinergics).

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

[35], [36], [37], [38], [39],

What medications are not available for pancreatitis?

Among the medicinal contraindications for the chronic form of pancreatitis are such drugs:

• tincture of alcohol;
• systemic antibiotics of the penicillin group, tetracycline, fluoroquinolones;
• sulfonamides (sulfadimezin, sulfazoline, etc.);
• diuretic drugs (loop, thiazide and saluretic);
• Warfarin and other indirect anticoagulants;
• preparations containing transretinic acid;
• agents based on valproic acid;
• glucocorticosteroids;
• adrenocorticotropic hormones
• any hormonal agents with estrogens;
• atypical antipsychotics.

In addition, it should be borne in mind that with acute pancreatitis and exacerbation of chronic, you can not take funds that replace the enzymes of the pancreas, that is, Pancreatin (and any of its synonyms).