Proton Pump Inhibitors Essay

Introduction
Proton pump inhibitors are one of the most prescribed classes of medication. They work by blocking the enzyme in the stomach that produces acid. By blocking the formation of this acid you are preventing such things like stomach and esophageal ulcers. Ulcers can lead to many health problems such as bleeding, holes through the wall of the stomach, and obstruction to the stomach or small intestine. Common proton pump inhibitors used to treat ulcers include omeprazole, esomeprazole, lansoprazole, and pantoprazole. CYP2C19 is the main isoenzyme that is responsible for the metabolism of omeprazole and esomeprazole. CYP2C19 has genetic polymorphisms that correlate with its activity1. As we learned about in class, individuals can be classified as poor metabolizers, extensive metabolizers, and ultra-rapid metabolizers. In this study, individuals were classified in these categories based on the CYP2C19 ability to metabolize proton pump inhibitors2. Individuals who carry CYP2C19*1/*1 are considered extensive metabolizers and have no mutation. Those who are homozygous for CYP2C19*2 or CYP2C19*3 are classified as intermediate or poor metabolizers. Lastly, those individuals who carry the CYP2C19*17 allele are classified as ultra-rapid metabolizers, and when given a standard recommended dose of proton pump inhibitors, they do not suppress acid production as well as they should3. These genetic polymorphisms of CYP2C19 can be taken into clinical consideration when prescribed a specific proton pump inhibitor when treating patients with peptic ulcers. The main purpose of this study is to observe the frequencies of CYP2C19*2, CYP2C19*3, and CYP2C19*17 alleles and genotypes in Russian patients with peptic ulcers1.
Methods
In this study 971 patients were studied. The patients were of Caucasian origin with Russian nationality from the Moscow region. All of the patients had to have a history of proven peptic ulcers. DNA was extracted from whole blood samples and then evaluated using real-time polymerase chain reaction. After analyzed, the patients were classified as poor metabolizers, extensive metabolizers, and ultra-rapid metabolizers according to the Dutch Pharmacogenetics Working Group Guideline of the Royal Dutch Pharmacist Association4. The distribution of genotype frequencies was assessed using the Hardy-Weinberg equilibrium.
Discussion
Of the 971 patients, 317 were classified as extensive metabolizers, 268 were either poor or intermediate metabolizers, and the remaining 386 were ultra-rapid metabolizers. The observed genotype frequencies were in the Hardy- Weinberg equilibrium for the majority of CYP2C19 polymorphisms1.
This specific study is a useful tool for personalized doses of proton pump inhibitors. The presence of peptic ulcers in difference countries varies around the world. Polymorphisms in CYP2C19 affect the cure rates of these peptic ulcers5. This study showed that patients who were classified as ultra-rapid metabolizers had lower levels of proton pump inhibitors in their plasma. If you were to genotype your patients before treatment you could modify their dose based on their classification or choose to provide a different form of therapy. This brings up the importance of precision medicine. Precision medicine takes into account the specific genes of an individual and how they can play a role the effectiveness of a given drug.