Clinical Treatment in IBD




© Springer International Publishing AG 2017
Jakub Fichna (ed.)Introduction to Gastrointestinal Diseases Vol. 110.1007/978-3-319-49016-8_9


9. Clinical Treatment in IBD



Marcin Włodarczyk1, 2   and Aleksandra Sobolewska-Włodarczyk1, 3  


(1)
Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland

(2)
Department of General and Colorectal Surgery, Faculty of Military Medicine, Medical University of Lodz, Lodz, Poland

(3)
Department of Gastroenterology, Faculty of Military Medicine, Medical University of Lodz, Lodz, Poland

 



 

Marcin Włodarczyk (Corresponding author)

Email:


 

Aleksandra Sobolewska-Włodarczyk (Corresponding author)

Email:


Abstract

Nowadays, treatment of IBD is still controversial. The management plan for a patient with Crohn’s disease should take into account the activity, site and behavior of disease, and should always be discussed with the patient. When deciding the appropriate treatment strategy for active ulcerative colitis, one should consider the activity, distribution and pattern of disease (relapse frequency, course of disease, response to previous medications, side-effect profile of medication and extra-intestinal manifestations). The age at onset and disease duration may also be important factors. Generally, in both diseases an individual approach to each patient cannot be neglected. The goal of the treatment, especially maintenance therapy, in both UC and CD is to achieve and maintain a steroid-free remission, clinically and endoscopically defined. In this chapter groups of drugs and their guidance for use will be discussed.


Keywords
Inflammatory bowel diseaseTreatmentSteroids5-ASAAnti-tumor necrosis factor alfa





  1. 1.


    Drugs in IBD treatment

     




  1. (A)


    Corticosteroids

     
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as their synthetic analogues. Corticosteroids are involved in a wide range of physiological processes, including stress response and immune response, regulation of inflammation, carbohydrate metabolism, and protein catabolism, blood electrolyte levels, and behavior [1–3].

Synthetic pharmaceutical drugs with corticosteroid-like effects are used in a variety of conditions, including IBD.

In the treatment of IBD hydrocortisone, budesonide and methylprednisolone are commonly in use.

Hydrocortisone:

(Hydrocortisone is a name for cortisol when it is used as a medication)



  • Stimulates gluconeogenesis (formation of glucose), and activates anti-stress and anti-inflammatory pathways.


  • Counteracts insulin; contributes to hyperglycemia, stimulating hepatic gluconeogenesis and inhibiting peripheral utilization of glucose (insulin resistance).


  • Reduces bone formation, favoring long-term development of osteoporosis (progressive bone disease).


  • Raises free amino acid levels in the serum.


  • Acts as a diuretic by increasing water diuresis, glomerular filtration rate, and renal plasma flow from the kidneys, as well as stimulating sodium retention and potassium excretion. It also increases sodium and water absorption and potassium excretion in the intestines [4, 5].

Budenoside:



  • Controls the rate of protein synthesis.


  • Depresses migration of polymorphonuclear leukocytes and fibroblasts


  • Reverses capillary permeability and lysosomal stabilization at the cellular level to prevent or control inflammation.


  • Has a potent glucocorticoid activity and weak mineralocorticoid activity [6–8].

Methylprednisolone:

The anti-inflammatory actions of methyloprednizolone are thought to involve phospholipase A2 inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes.

Side effects of corticosteroids:



  • increased appetite


  • acne


  • rapid mood swings and mood changes—such as becoming aggressive, irritable and short-tempered with people


  • thin skin that bruises easily


  • muscle weakness


  • delayed wound healing


  • a combination of fatty deposits that develop in the face, stretch marks across the body and acne—known as the Cushing’s syndrome


  • weakening of the bones (osteoporosis)


  • diabetes (or they may worsen existing diabetes)


  • high blood pressure


  • glaucoma and cataracts (eye conditions)


  • stomach ulcers—one may be prescribed an additional medication called a proton pump inhibitor (PPI) to reduce this risk


  • increased risk of infections, particularly chickenpox, shingles and measles


  • reduced growth in children [9, 10].




  1. (B)


    Derivatives of 5-aminosalicylic acid (5-ASA): mesalazine and sulfasalazine

     
Mesalazine or 5-aminosalicylic acid is a bowel-specific aminosalicylate drug that acts locally in the gut and has its predominant actions there, thereby having few systemic side effects. As a derivative of salicylic acid, mesalazine is also thought to be an antioxidant that traps free radicals, which are potentially damaging byproducts of metabolism. An active moiety of sulfasalazine, which is metabolized to sulfapyridine and mesalazine.

Sulfasalazine and its metabolite 5-ASA are poorly absorbed from the small intestine; its main mode of action is therefore believed to be inside the intestine. Approximately one third of a dose of sulfasalazine is absorbed from the small intestine. The remaining two thirds pass into the colon where the drug is split by bacteria into 5-ASA and sulfapyridine. Sulfapyridin eis well absorbed from the colon (estimated bioavailability 60 %); 5-ASA is less well absorbed (estimated bioavailability 10–30 %).

Side effects of 5-ASA:



  • Diarrhea


  • Nausea


  • Cramping


  • Flatulence


  • Headache


  • Hypersensitivity reactions (including rash, urticaria aka hives, interstitial nephritis and lupus erythematosus-like syndrome)


  • Hair loss


  • Acute pancreatitis


  • Hepatitis


  • Nephrotic syndrome


  • Blood disorders (including agranulocytosis, aplastic anaemia, leukopenia, neutropenia, thrombocytopenia).

Mesalazine avoids the sulfonamide side effects of sulfasalazine, which contains additional sulfapyridine, but carries additional rare risks of: allergic lung reactions, allergic myocarditis, methaemoglobinaemia [11–14].


  1. (C)


    Thiopurines: azathioprine, tioguanine, mercaptopurine

     

The thiopurine drugs are purine antimetabolites widely used in the treatment of the inflammatory disease.

The purine molecule is the framework for two of the four bases that occur in DNA, adenine and guanine. Consequently, blocking the synthesis of purine also hinders DNA synthesis and thus inhibits the proliferation of cells, especially fast-growing cells without a method of nucleotide salvage (“recycling”), such as lymphocytes—T-cells and B-cells.

Azathioprine

The active metabolite of azathioprine, methyl-thioinosine monophosphate is a purine synthesis inhibitor that works by blocking the enzyme amidophosphoribosyltransferase.

Side effects of thiopurine:



  • Nausea and vomiting (especially at the beginning of the treatment).


  • Hypersensitivity reactions include dizziness, diarrhea, fatigue, and skin rashes.


  • Hair loss.


  • Bone marrow suppression (anaemia).


  • Susceptibility to infection.


  • Acute pancreatitis can also occur, especially in patients with Crohn’s disease [15–21].




  1. (D)


    Methotrexate

     
Methotrexate is an antimetabolite and an antifolate drug. Methotrexate competitively inhibits dihydrofolate reductase (DHFR), an enzyme that participates in the tetrahydrofolate synthesis. Methotrexate inhibits the synthesis of DNA, RNA, thymidylates, and proteins. This drug also takes part in the inhibition of enzymes involved in purine metabolism, leading to accumulation of adenosine, inhibition of T cell activation and suppression of intercellular adhesion molecule expression by T cells, selective down-regulation of B cells, increasing CD95 sensitivity of activated T cells, and inhibition of methyltransferase activity, leading to (de)-activation of enzyme activity relevant to immune system function. Another mechanism of MTX is the inhibition of the binding of interleukin 1-beta to its cell surface receptor.

Side effects of methotrexate:



  • Hepatotoxicity (liver damage)


  • Ulcerative stomatitis


  • Bone marrow suppression—low white blood cell count and thus predisposition to infection


  • Nausea, abdominal pain, fatigue


  • Fever


  • Acute pneumonitis, rarely pulmonary fibrosis


  • harmful to fetus (pregnancy category X) [22–24].




  1. (E)


    Cyclosporine

     
Cyclosporine binds to the cytosolic protein cyclophilin of lymphocytes, especially T cells. The complex of cyclosporine and cyclophilin inhibits calcineurin, which, under normal circumstances, is responsible for activating the transcription of interleukin 2.

Side effects of cyclosporine.



  • Enlargement of the gums


  • Convulsions


  • Peptic ulcers


  • Pancreatitis


  • Hypercholesterolemia


  • High blood pressure


  • Potassium retention possibly leading to hyperkalemia


  • Nephrotoxicity and hepatotoxicity [25–27].




  1. (F)


    Tacrolimus

     
Tacrolimus is an anti-inflammatory drug inhibiting the production of interleukin-2, a molecule that promotes the development and proliferation of T cells. Tacrolimus is a macrolide calcineurin inhibitor.

Side effects of tacrolimus:



  • Infection


  • Cardiac damage


  • Hypertension


  • Blurred vision


  • Nephrotoxicity


  • Hyperkalemia, hypomagnesemia


  • Hyperglycemia, diabetes mellitus


  • Lung damage


  • Various neuropsychiatric complications [28, 29].




  1. (G)


    Anti-tumor necrosis factor alfa agents

     
Anti-tumor necrosis factor alpha agent (anti-TNF-alpha) is a pharmaceutical drug that suppresses the immune system. TNF-alpha is involved in autoimmune and immune-mediated disorders. In IBD pathogenesis, TNF-alpha is one of the most important cytokines.

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Jun 30, 2017 | Posted by in GASTOINESTINAL SURGERY | Comments Off on Clinical Treatment in IBD

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