Sulfonamides pancreatitis with

The manufacturers of didanosine have a similar recommendation and state that, if concurrent use is unavoidable, there should be close observation. Similarly, other authors recommend temporarily discontinuing didanosine in patients needing systemic pentamidine or sulfonamide-containing regimens. The UK manufacturer of stavudine recommends that patients receiving concurrent treatment with drugs known to cause pancreatitis should be carefully observed, and the US manufacturer specifically recommends caution with combined use of didanosine and stavudine, see NRTIs + NRTIs , p.800. Note that hydroxycarbamide (hydroxyurea) may increase the risk of pancreatitis with didanosine and stavudine, and the combination should probably be avoided, see NRTIs + Hydroxycarbamide , p.799. 

The thiazides are sulfonamides and share cross-reactivity with other members of this chemical group. Photosensitivity or generalized dermatitis occurs rarely. Serious allergic reactions are extremely rare but do include hemolytic anemia, thrombocytopenia, and acute necrotizing pancreatitis. 

Co-trimoxazole can cause reversible hypoglycemia, which may be prolonged, particularly in patients with risk factors for hypoglycemia. Common risk factors include compromised renal function, prolonged fasting, malnutrition, and the use of excessive doses. It has been postulated that the sulfonamide mimics the action of sul-fonylureas, stimulating pancreatic islet cells to secrete insulin. In elderly people, co-trimoxazole-induced hypoglycemia can cause altered mental state (1146,1147). 

Pancreatic cholesterol esterase (3.1.1.3.) aids in transporting cholesterol to the enterocyte. By utilizing a selective and potent cholesterol esterase inhibitor 6-chloro-3-(l-ethyl-2-cyclohexyl)-2-pyrone, the absorption of cholesterol in hamsters could be reduced [71]. Wadkins et al. [72] synthesized novel sulfonamide derivatives, which demonstrated greater than 200-fold selectivity for human intestinal carboxylesterase compared with the human liver carboxylesterase hCEl, and none of them was an inhibitor of human acetylcholinesterase or butyrylcholinester-ase. Maybe these agents can serve as lead compounds for the development of effective, selective carboxylesterase inhibitors for clinical applications. Also the potent P-gp inhibitor verapamil [73] as well as S,S,S-tributylphosphortrithionate (DEF) [74] may exhibit carboxylesterase inhibitory properties. Various other inhibitors of human esterases are listed in Table 5.6. 

Several agents have been associated with producing acute pancreatitis or inflammation of the pancreas. The main causes are alcohol and a disturbance of the bile duct, which account for 50% of cases. Drugs with a clear association include sulfonamides, thiazide diuretics, tetracycline, azathioprine, estrogens, and valproic acid. The mechanism for the underlying injury is not well understood. Possible associations have been reported with other medications including methyldopa, procainamide, and 1-asparaginase. A relationship between cortico-steriods has not been established. 

Adverse effects that are not dose related most commonly include rash, fever, or hepatotoxicity, as well as relatively uncommon but serious reactions such as bone marrow suppression, thrombocytopenia, pancreatitis, and hepatitis. For most patients with idiosyncratic reactions, sulfasalazine must be discontinued. In some patients who have experienced allergic reactions to sulfasalazine, a desensitization procedure can be instituted. By gradually increasing sulfasalazine dosage over weeks to months, patient tolerance has been improved. Most of the idiosyncratic reactions observed with sulfasalazine are similar to those with the class of sulfonamides in general. 

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