Pancreatic reactions

LY311727 is an indole acetic acid based selective inhibitor of human non-pancreatic secretory phospholipase A2 (hnpsPLA2) under development by Lilly as a potential treatment for sepsis. The synthesis of LY311727 involved a Nenitzescu indolization reaction as a key step. The Nenitzescu condensation of quinone 4 with the p-aminoacrylate 39 was carried out in CH3NO2 to provide the desired 5-hydroxylindole 40 in 83% yield. Protection of the 5-hydroxyl moiety in indole 40 was accomplished in H2O under phase transfer conditions in 80% yield. Lithium aluminum hydride mediated reduction of the ester functional group in 41 provided the alcohol 42 in 78% yield. 

Adverse reactions reported with didanosine include headache, peripheral neuropathy, rhinitis, cough, diarrhea, nausea, vomiting, anorexia, hepatotoxicily, and pancreatitis. 

DIDANOSINE Although rare, pancreatitis and peripheral neuropathy are possible adverse reactions seen with didanosine The nurse must be alert for symptoms of pancreatitis (nausea, vomiting, abdominal pain, jaundice, elevated enzymes) and for signs of peripheral neuropathy (numbness, tingling, or pain in the feet or hands). It is important to immediately report these signs to the primary health care provider. 

This lactamization process can be promoted by enzymes such as pancreatic porcine lipase. Reduction of co-azido carboxylic acids leads to macrocyclic lactams. Although treatment of carboxylic acids with amines does not directly give amides, the reaction can be made to proceed in good yield at room temperature or... 

Depending on the nature of the compound, the ddN analogues have been associated with varying toxic side effects such as bone marrow suppression (AZT), pancreatitis (ddl), hypersensitivity reactions (ABC), and neurologic complications consequently to mitochondrial toxicity (ddC), while others, such as 3TC and (-)FTC, have few, if any, side effects. 

Immobilized PLE was applied to promote stereoselective acetylation of prochiral bis(hydroxymethyl)methyl-phenylgermane 106 (R = Me) with vinyl acetate as a solvent and acyl donor. Later on, the same group reported that each enantiomer of hydridogermane monoacetates 107 (R = H) was obtained either via acetylation of the bis-hydroxy derivative 106 (R = H) or hydrolysis of the corresponding diacetate 108 (R = H). In both methods, porcine pancreatic lipase was used and, obviously, each reaction led to a different enantiomer of 107 (Equation 51). ... 

Generally, the major adverse effects associated with colloids are fluid overload, dilutional coagulopathy, and anaphy-lactoid/anaphylactic reactions.24,32 Although derived from pooled human plasma, there is no risk of disease transmission from commercially available albumin or PPF products since they are heated and sterilized by ultrafiltration prior to distribution.24 Because of direct effects on the coagulation system with the hydroxyethyl starch and dextran products, they should be used cautiously in hemorrhagic shock patients. This is another reason why crystalloids maybe preferred in hemorrhagic shock. Furthermore, hetastarch can result in an increase in amylase not associated with pancreatitis. As such, the adverse-effect profiles of the various fluid types should also be considered when selecting a resuscitation fluid. 

Agents targeting the excessive immune response or cytokines involved in IBD are potential treatment options (Table 16-3). Azathioprine and its active metabolite 6-mercaptopurine (6-MP) are inhibitors of purine biosynthesis and reduce IBD-associated GI inflammation. They are most useful for maintaining remission of IBD or reducing the need for long-term use of corticosteroids. Use in active disease is limited by their slow onset of action, which may be as long as 3 to 12 months. Adverse effects associated with azathioprine and 6-MP include hypersensitivity reactions resulting in pancreatitis, fever, rash, hepatitis, and leukopenia.25,26... 

With azathioprine and 6-MP, monitor for hypersensitivity reactions, including severe skin rashes and pancreatitis. Educate the patient regarding signs and symptoms of pancreatitis (nausea, vomiting, and abdominal pain). 

Hypersensitivity reactions (fever, hypotension, rash, dyspnea in 25%), much lower risk with polyethylene gycol form low emetogenic potential pancreatitis decreased synthesis of proteins, clotting factors CNS lethargy... 

Moberg L, Johansson H, Lukinius A et al (2002) Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Lancet 360 2039-2045... 

Non-dose-related adverse effects of sulfasalazine include rash, fever, or hepatotoxicity most commonly, as well as relatively uncommon but serious reactions such as bone marrow suppression, thrombocytopenia, pancreatitis, pneumonitis, interstitial nephritis, and hepatitis. 

Immunosuppressants such as azathioprine and mercaptopurine have a significant potential for adverse reactions, including bone marrow suppression, and have been associated with lymphomas (in renal transplant patients) and pancreatitis. Myelosuppression resulting in leukopenia is related to a deficiency in TPMT in some patients. 

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