Treatment of Pancreatic Insufficiency due to Cystic Fibrosis - Research Paper Example

? Treatment of Pancreatic Insufficiency due to Cystic Fibrosis Teacher               Treatment of Pancreatic Insufficiency due to Cystic Fibrosis Cystic fibrosis (CF) is a rare inborn autosomal recessive disease common among people of Northern and Central Europe. CF is all about the problem of mutation of the cystic fibrosis transmembrane conductance regulator or CFTR gene, which makes possible the secretion of the protein that regulates body fluids like digestive fluids, sweat and mucus. The result of the disease is therefore the inefficiency of the chloride and sodium transport system of certain internal organs like the lungs, liver, intestine and pancreas. The pancreas is definitely affected by CF. Aside from the proper breakdown of insulin, the pancreas is responsible for the production of digestive enzymes that help break down ingested food. An inability to do this is known as exocrine pancreatic inefficiency (EPI), which is another serious condition brought about by CF. EPI is also characterized by an “impaired digestion and decreased absorption of nutrients,” both of which leading to poor nutritional status among those with CF (Wooldridge et al., 2009). There are also other symptoms of EPI that include pain, bloating, flatus, steatorrhea, and malabsorption (Wooldridge et al., 2009). Although EPI is common in dogs, it occasionally occurs in humans through CF and Shwachman-Diamond Syndrome. For those with EPI due to CF, studies have shown that the best solution is pancreatic enzyme products, or PEP. The pancreatic enzyme product, or PEP, known as EUR-1008, or Zenpep pancrelipase, has been proven to be an effective treatment against EPI in patients with CF (Wooldridge et al., 2009). EUR-1008 is in the form of “enteric-coated microspheres of porcine enzyme concentrate” occurring in capsule form that can be orally administered, and available in 5000, 10000, 15000 or 20000 units. Treatment using EUR-1008 was administered to confirmed CF patients who were diagnosed with EPI and who were both less than and more than 7 years of age. The diet of the patients was also controlled and was required to maintain a minimum of 100g of fat. The experimental study yielded positive results in terms of the positive changes in the coefficient of fat absorption, or CFA, in the coefficient of nitrogen absorption, or CNA, and in the alleviation of the signs and symptoms of malabsorption of food. The data for CFA and CAN were measured using a 72-hour stool sample. The significantly higher mean for both CFA and CAN compared to placebo trials proved the effectiveness of EUR-1008 in the treatment of EPI caused by CF. There were also noteworthy physiological changes in the patients that included improvements in the vital signs, weight, BMI, and QOL assessments which proved better than before the administration of EUR-1008. Moreover, EUR-1008 had no known adverse effects reported during the study and was also well-tolerated and safe. The best thing about it is that it proved to be efficient in patients of all ages (Wooldridge et al., 2009). As EPI was positively dealt with by EUR-1008 in patients of all ages, it can also be treated using pancreatic enzyme replacement therapy, or PERT, in children with CF and aged 7 to 11 years old (Graff et al., 2010). PERT consisted of the administration of “pancrelipase delayed-release 12,000-lipase unit capsules” to the children (Graff et al., 2010). Since the study was conducted across 10 health centers in the United States, there was a strict daily monitoring of the symptoms and dietary intake by properly trained staff. Among the 16 patients who completed the experimental study, all had improved CFA and CNA values compared with placebo trials. CFA for the PERT capsules had values of 82.8% while placebo had only 47.4%. CNA for PERT capsules were recorded at 80.3% compared to placebo values at 45.0%, thus obviously proving that PERT was indeed effective in the treatment of EPI in children with CF. Moreover, aside from the improvements in CFA and CNA, there were also significant improvements in weight and stool fat as well as the overall condition of EPI. Just like EUR-1008, there were also no records of any adverse event associated with PERT, or specifically with the pancrelipase delayed-release capsules. So far, the only limitation of the study was only the restricted age of the subjects, thus the efficacy of PERT in adults is not guaranteed except in the next study (Graff et al., 2010). The efficacy of PERT in adults is proven by the study that investigated the use of PANCREAZE, or pancrelipase, as treatment for 48 CF patients with EPI and of varying ages from 7 to 60 as confirmed by a sweat test or a genotype analysis (Trapnell et al., 2011). The PANCREAZE, or pancrelipase, drug is prescribed for patients with CF of all ages – infants, children and adults. It is available in 10.5 and 21 dosages and occurs in capsule form. PANCREAZE is an oral pancreatic enzyme supplement that contains microtablets of enzymes that have been extracted from porcine pancreas. PANCREAZE contains the enzymes lipase, amylase and protease. Although there was not much restriction based on age, there was a strict prohibition of the patient from using mineral oil, magnesium, other enzyme preparations, potassium supplementation and polyethylene glycol. Once more, just like in the two previously mentioned drugs, PANCREAZE also proved to be effective in terms of CFA and CNA compared to placebo trials. Moreover, there were also significant improvements in terms of alleviation of the usual symptoms of EPI such as abdominal pain, flatulence, abnormal stools and diarrhea, all of which occurred less in patients with administered PANCREAZE. Furthermore, just like in the other previously mentioned studies, there were no serious adverse events found in all 48 patients with CF and EPI, except for a few cases of gastrointestinal disturbance. Therefore, through the results of this study, PANCREAZE proved to be the drug of choice for infants, children, adolescents and adults with CF and EPI. There may be efficacy differences when it comes to age, but that is supposed to be the subject of another study (Trapnell et al., 2011). A comparison of Creon 10000 Minimicrospheres, or Creon 10000 MMS, and Creon 8000 conventional microspheres, or Creon 8000 ms, proves that children prefer Creon 10000 MMS to Creon 8000 ms (Patchell et al., 2002). Fifty-one out of 54 patients preferred Creon 10000 MMS to Creon 8000 ms. Nevertheless, there was no clear treatment differences between the two Creon drug types in terms of stool consistency and frequency, abdominal pain and flatulence. These were the findings of the 2002 study despite the results of a past German study where Creon 10000 MMS was shown to result in an improved pulmonary function and steatorrhea. Overall, the findings of this 2002 study on why people generally preferred Creon 10000 MMS is most likely the smaller size of the capsule which is actually more acceptable and relatively much easier to swallow (Patchell et al., 2002). Nevertheless, if the study were to be made into an experimental one, there would be a chance that Creon 10000 MMS would prove to be therapeutically better than Creon 8000 ms, as proven by a previous German study. The findings of the four previously mentioned studies have actually been confirmed by the Cystic Fibrosis Foundation, which confirmed the efficacy of pancreatic enzyme preparations, or PEP, in order to alleviate the conditions brought about by EPI in patients with CF (Stallings et al., 2008). According to the review, whether it is for children with CF, for adolescents or for adults, the recommended drug of choice for those with EPI is the “nongeneric, proprietary pancreatic enzyme preparations” (Stallings et al., 2008). Nevertheless, it was also emphasized by the review that there should be routine energy intake as well as combined behavioral and nutritional intervention as well as strict nutritional supplementation for patients with CF and EPI. Moreover, the review is a call to action for all CF centers across the United States as well as CF affiliate programs to maintain BMI recommendations of the Cystic Fibrosis Foundation, and to adopt the recommended therapeutic procedures for CF patients with EPI (Stallings et al., 2008). The gravity of cystic fibrosis and the seriousness of exocrine pancreatic insufficiency may indeed cause so much physical and physiological discomfort in the patient. Nevertheless, the introduction of pancreatic enzyme products is crucial to the alleviation of adverse symptoms brought about by EPI. These drugs, which are generally recommended by a review article on the Cystic Fibrosis Foundation, include EUR-1008, pancrelipase delayed-release capsules, PANCREAZE and Creon 10000 MMS. The first four are preferred because of their significant effects on the CFA and CNA levels of the patient as well as in other observable physical and physiological aspects like stool consistency and frequency, improved weight, and alleviated pain and diarrhea. Creon 10000 MMS is preferred because of the convenience in swallowing it due to its small size. Overall, however, strict monitoring of diet as well as adequate energy intake is emphasized by the Cystic Fibrosis Foundation in order to ensure a greater alleviation of symptoms of EPI in addition to the use of PEP. References Graff, G. R., Maguiness, K., McNamara, J., Morton, R., Boyd, D., Beckmann, K. & Bennett, D. (2010). Efficacy and Tolerability of a New Formulation of Pancrelipase Delayed-Release Capsulesin Children Aged 7 to 11 Years With Exocrine Pancreatic Insufficiency and Cystic Fibrosis: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Two-Period Crossover, Superiority Study. Clinical Therapeutics, 32(1), 89-103. Patchell, C. J., Desai, M., Weller, P. H., MacDonald, A., Smyth, R. L., Bush, A., Gilbody, J. S. & Duff, S. A. (2002). Creon 10000 Minimicrospheres vs. Creon 8000 microspheres – an open randomized crossover preference study. Journal of Cystic Fibrosis, 1, 287-291. Stallings, V. A., Stark, L. J., Robinson, K. A., Feranchak, A. P. & Quinton, H. (2008). Evidence-Based Practice Recommendations for Nutrition-Related Management of Children and Adults with Cystic Fibrosis and Pancreatic Insufficiency: Results of a Systematic Review. Journal of the American Diet Association, 108, 832-839. Trapnell, B. C., Strausbaugh, S. D., Woo, M. S., Tong, S., Silber, S. A., Mulberg, A. E. & Leitz, G. (2011). Efficacy and safety of PANCREAZE for treatment of exocrine pancreatic insufficiency due to cystic fibrosis. Journal of Cystic Fibrosis, 10, 350-356. Wooldridge, J. L., Heubi, J. E., Amaro-Galvez, R., Boas, S. R., Blake, K. V., Nasr, S. Z., Chatfield, B., McColley, S. A., Woo, M. S., Hardy, K. A., Kravitz, R. M., Straforini, C., Anelli, M. & Lee, C. (2002). EUR-1008 pancreatic enzyme replacement is safe and effective in patients with cystic fibrosis and pancreatic insufficiency. Journal of Cystic Fibrosis, 8, 405-417. Read More