Drug-induced pancreatitis

In recent decades, due to significant developments in pharmacology and the increasingly widespread use of highly active drugs in clinical practice, reports of their side effects, in particular, of the damaging effect on the pancreas in some cases, have begun to appear more and more frequently. The first reports of this kind began to appear in the 1950s, and then their number increased. In Russian literature, attention to drug-induced pancreatitis was drawn by V. M. Laschevker (1981), who published a large review on the topic.

The first reports of side effects of drugs on the pancreas concerned corticosteroids prescribed for various, rather severe and painful diseases: bronchial asthma, rheumatoid arthritis, pemphigus, thrombocytopenic purpura, aplastic anemia, etc.

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Causes of drug-induced pancreatitis

In patients receiving corticosteroids, "steroid" pancreatitis developed, often severe, occurring as pancreatic necrosis, in some cases ending fatally. A number of the first descriptions of fatal pancreatic necrosis were noted in children treated with corticosteroids, in whom pancreatitis is very rare.

In addition to cases of acute pancreatitis, some patients had disorders of the exocrine and, more often, endocrine functions of the pancreas ("steroid" diabetes mellitus). The pathogenesis of pancreatic damage in these cases is not clear enough and, apparently, has a different basis in different patients. Some patients have a peculiar allergic reaction to the administration of the drug, in other cases - focal tissue destruction, with long-term use of the drug, interstitial inflammation and fibrosis were noted.

Other drugs that cause damage to the pancreas include ACTH, estrogens and estrogen-containing contraceptives, diuretics (furosemide, hypothiazide, uregit, etc.). After discontinuing diuretics, some patients experienced rapid relief of pancreatitis symptoms. It is believed that one of the causes of pancreatitis during diuretic therapy is hypokalemia. However, P. Banks (1982) does not exclude the possibility that the main cause of pancreatitis during diuretic treatment may be hypovolemia caused by them.

Pancreatitis also develops with an overdose of drugs containing calcium and vitamin D. The relationship between the pathology of the parathyroid and pancreatic glands was previously studied in detail by V. M. Lashchevker.

Rifampicin, tetracycline, and some sulfanilamide drugs are mentioned among antibacterial drugs that have caused acute pancreatitis in some cases. Damage to the pancreas, including acute pancreatitis and pancreatic necrosis, has been described in the treatment with salicylates, indomethacin, paracetamol, immunosuppressants (azathioprine, etc.), meprobamate, clonidine, and many others.

Thus, many medications are capable of having a side damaging effect on the pancreas. However, this side effect is most often encountered in treatment with adrenal cortex preparations and their analogues, so often that this side effect ("steroid" pancreatitis, "steroid" diabetes) is even necessarily indicated in information materials on these drugs and in reference manuals [Mashkovsky M.D., 1993, and others].

However, without questioning the possibility of acute and chronic pancreatitis when using modern effective drugs for various other diseases, one should take into account the "previous background" - the presence of chronic pancreatitis or episodes of acute (or exacerbations of chronic) in the past, the presence of chronic cholecystitis or cholelithiasis, which are known to be often combined with inflammatory diseases of the pancreas, alcoholism and some other factors. So it is necessary in each specific case not to directly connect, possibly completely independent phenomena:

1. taking certain medications and the development of chronic pancreatitis due to other causes;
2. provoking an exacerbation of an existing disease by a drug;
3. the effect of a drug on an intact pancreas, either directly or as a result of an allergic reaction or individual intolerance, in which the “weakest” organ in terms of the damaging effects of certain exogenous toxic factors is precisely the pancreas.

This may be due to a certain hereditary predisposition, a genetically determined defect of certain cellular systems. It should also be borne in mind that some diseases, in particular those of the rheumatic group (rheumatoid arthritis, systemic lupus erythematosus, rheumatism, periarteritis nodosa, etc.), which are most often treated with corticosteroid hormones, are already systemic in nature with damage to many organs, including the pancreas. Therefore, it is hardly legitimate to attribute all cases of acute pancreatitis that arose during drug therapy for these (and many other) diseases as a result of drug therapy.

It is difficult to judge the mechanisms of occurrence of hemorrhagic pancreatitis in patients receiving immunosuppressive drugs after kidney transplantation: in which cases is the occurrence of pancreatic necrosis associated with this very difficult operation, and in which cases - with drugs?

It should be borne in mind that medications, in particular steroid hormones (and some other drugs), which were well tolerated in the past, when prescribed again can suddenly, literally within a few minutes, cause severe pancreatic necrosis [Baor H., Wolff D., 1957], in this and similar cases, an allergic genesis of the pancreatic lesion is undoubtedly traced. It should be noted that in the medical literature, authors, as a rule, describe only isolated observations of drug-induced pancreatitis, from which it is difficult to make generalizations regarding specific mechanisms of development of drug-induced pancreatitis; this issue, due to its importance, requires special studies.

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Symptoms and diagnosis of drug-induced pancreatitis

The clinical picture in the most typical cases is quite vivid: immediately after taking (or administering) a drug, sharp pains occur in the epigastric region and in the left hypochondrium. Other manifestations of drug allergy or toxic-allergic lesions of other organs are also often noted. Drug-induced damage to the subpancreas in these cases usually occurs as acute necrotic (hemorrhagic) pancreatitis. Many authors point to rapidly developing hyperfermentemia (increased serum levels of pancreatic enzymes) and high amylase. In other cases, the pathological process in the pancreas in response to taking or administering drugs develops more gradually and resembles subacute or chronic pancreatitis in its clinical manifestations and course.

A very important sign confirming drug-induced damage to the pancreas, which some authors point to, is the rapid subsidence of signs of damage to the gland upon discontinuation of the drug and their reappearance after repeated administration.

Treatment, prevention of drug-induced pancreatitis

In severe cases, hospitalization is mandatory. If there is certainty or even just a suspicion that the damage to the pancreas is somehow related to the intake (or parenteral administration) of some medication, it should be immediately discontinued. Treatment of drug-induced damage to the pancreas is carried out according to the general principles of treatment of acute and chronic pancreatitis (depending on the severity of the process); in the presence of an allergic reaction - appropriate therapy.

In the prevention of drug-induced pancreatic damage, a carefully collected allergological and “drug” anamnesis, careful gradual monitoring of drug therapy, its effectiveness and timely detection of possible side effects, in particular the first signs of damage to the pancreas, are of great importance.