Medicinal pancreatitis

In recent decades, due to the significant development of pharmacology and the increasing use of highly active drugs in clinical practice, there have been increasing reports of their side effects, in particular, and of the damaging effect in some cases on the pancreas. The first reports of this kind began to appear in the fifties of this century, then they became more and more. In the domestic literature, attention was drawn to medicinal pancreatitis by VM Lashchevker (1981), who published a large review on this topic.

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

[1], [2], [3], [4]

Causes of drug pancreatitis

In patients receiving corticosteroids, there were "steroid" pancreatitis, often severe, proceeding in the type of pancreatic necrosis, in some cases ended lethal. A number of the first descriptions of the fatal pancreatic necrosis were observed in children treated with corticosteroids, in which pancreatitis is very rare.

In addition to cases of acute pancreatitis, in a number of patients there were violations of the exocrine and more often endocrine function ("steroid" diabetes mellitus) of the pancreas. The pathogenesis of pancreatic damage in these cases is not clear enough and, apparently, varies from patient to patient. In some patients, there is a peculiar allergic reaction to the administration of the drug, in other cases - focal destruction of the tissue, with prolonged use of the medication, interstitial inflammation and fibrosis were noted.

Among other drugs that cause pancreatic damage, mention ACTH, estrogens and estrogen-containing contraceptives, diuretics (furosemide, hypothiazide, ureitis, etc.). After the abolition of diuretics, a rapid subsidence of the symptoms of pancreatitis was noted in some patients. It is believed that one of the reasons for the development of pancreatitis against a background of diuretic therapy is hypokalemia. However, P. Banks (1982) does not rule out the possibility that the main reason for the development of pancreatitis in the treatment of diuretics may be the hypovolemia caused by them.

Pancreatitis also develops with an overdose of drugs containing calcium, vitamin D. The relationship between parathyroid and pancreatic pathology was previously studied in detail by VM Lashchevkar.

Among antibacterial drugs, against which in some cases there was acute pancreatitis, mention rifampicin, tetracycline, some sulfonamide drugs. Damage to the pancreas, including acute pancreatitis and pancreatic necrosis, has been described in the treatment of salicylates, indomethacin, paracetamol, immunosuppressants (azathioprine, etc.), meproprobamate, clonidine and many others.

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

Nevertheless, without questioning the possibility of the emergence of acute and chronic pancreatitis in the application of modern effective drugs to various other diseases, one should take into account the "previous background" - the presence in the past of chronic pancreatitis or episodes of acute (or exacerbations of chronic), the presence of chronic cholecystitis or cholelithiasis diseases are known to often combine with inflammatory diseases of the pancreas, alcoholism and some other issues. So it is necessary not to directly link in each specific case, perhaps completely independent phenomena:

1. taking certain medications and the occurrence of chronic pancreatitis due to other causes;
2. the provocation of an exacerbation of an existing disease by the medicine;
3. the effect of the drug on the undamaged pancreas directly or as a result of an allergic reaction, or its individual intolerance, in which the "weakest" organ in terms of the damaging effect of certain exogenous toxic factors is precisely the pancreas.

Perhaps this is due to a certain hereditary predisposition, a genetically conditioned defect of one or another cellular system. It should also be borne in mind that some diseases, in particular the rheumatic group (rheumatoid arthritis, systemic lupus erythematosus, rheumatism, nodular periarteritis, etc.), which are most often treated with corticosteroid hormones, are already systemic in nature, with damage to many organs, including the pancreas. Therefore, to attribute all cases of acute pancreatitis that occurred during the period of drug therapy for these (and many other) diseases, as a result of drug therapy is unlikely to be qualified.

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

It should be borne in mind that drugs, in particular steroid hormones (and some other drugs) that have been well tolerated in the past, can suddenly, in a few minutes, cause severe pancreatonecrosis [Baor H., Wolff D., 1957] , in this and similar cases, undoubtedly, the allergic genesis of pancreatic lesion is traced. It should be noted that in the medical literature the authors, as a rule, describe only single observations of medicinal pancreatitis, according to which it is difficult to make generalizations concerning specific mechanisms for the development of medicinal pancreatitis; this issue, due to its importance, requires special research.

[5], [6], [7], [8], [9], [10]

Symptoms and Diagnosis of Medicinal Pancreatitis

The clinical picture in the most typical cases is very bright: immediately after the reception (or administration) of the drug there are sharp pains in the epigastric region and in the zone of the left hypochondrium. Other manifestations of drug allergy or toxicoallergic lesions of other organs are often noted. Drug damage under the gastric gland in these cases usually proceeds according to the type of acute necrotic (hemorrhagic) pancreatitis. Many authors point to the rapidly emerging hyperenzyme (increased serum levels of pancreatic enzymes) and high amylasuria. In other cases, the pathological process in the pancreas, in response to the administration or administration of medications, develops more gradually and, in its clinical manifestations and flow, resembles subacute or chronic pancreatitis.

A very important sign that confirms the pancreatic drug lesion, pointed out by some authors, is the rapid subsidence of the signs of the lesion of the gland when the drug is withdrawn and re-emergence after re-appointment.

Treatment, prevention of medicinal pancreatitis

In severe cases, hospitalization is mandatory. If there is confidence or even just a suspicion that a pancreatic lesion is somehow related to the taking (or parenteral administration) of some medicine, it must be immediately withdrawn. Treatment of medicinal lesions of 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 medicinal pancreatic lesions, a carefully collected allergic and "medicinal" history, careful gradual monitoring of the drug therapy, its effectiveness and timely detection of possible side effects, in particular the first signs of pancreatic damage, are of great importance.