l22_case_sdy_omp

l22_case_sdy_omp - 20.201 Lecture 22 Page 4 H Pylori...

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20 .201 Lecture # 22 11/14/05 Page 1 Lecture # 22 : Omeprazole Case Study November 14, 2005 20 .201 Mechanisms of Drug Action
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20 .201 Lecture # 22 11/14/05 Page 2 Other drugs metabolized by CYP2C19 • Diphenylhydantoin - ~ antiepileptic ~ 10-20% of the metabolism ~ CYP2C9 accounts for bulk • Diazepam - ~ anxiolytic ~ prolonged sedation in mutants • Proguanil - antimalarial • Cialopram - antidepressant (selective seratonin reuptake inhibitor) • Some barbiturates
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20 .201 Lecture # 22 11/14/05 Page 3 Polymorphisms in CYP2C9 • Rarer than CYP2C19 polymorphisms •Arg 144 to Cys 144 : ~ diminished activity ~ 8% Caucasians; absent in Asians •I le 359 to Leu 359 : ~ higher K m /lower V max ~ Homozygous 0.3% Caucasians; Hetero 6% • Major effect, though, due to metabolism of drugs with narrow therapeutic windows: ~ Warfarin - anticoagulant ~ Glipizide - type II diabetes ~ Tolbutamide - type II diabetes ~ Phenytoin - antiepileptic (80-90%) NH HN O O Warfarin Phenytoin (Dilantin) S N H N H O O O R1 R1 R R Name Tolbutamide Glipizide CH 3 H 3 C CH 2 CH 2 CH 2 CH 3 N N NHCH 2 CH 2 - O
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Unformatted text preview: 20 .201 Lecture # 22 11/14/05 Page 4 H. Pylori treatment and CYP2C19 Polymorphisms Furuta et al. Annals Int. Med. 129 : 1027-1030, 1998 • H. pylori infection associated with ulcers and high risk of gastric cancer • Previous ulcer treatments focused solely on the acid production • Now add antibiotic regimen to ulcer treatment • Furuta et al. used combination of amoxicillin and omeprazole to treat H. pylori infection in Japanese patients displaying range of CYP2C19 polymorphisms H. Pylori EM H. Pylori EM Amoxicillin Image of H. Pylori immunostaining in stomach lining removed due to copyright restrictions. Peptic ulcers may lead to bleeding or perforation, emergency situations Figure by MIT OCW. Gastritis Bacteria White blood cell Inflammation Heliobacter Pylori Bacteria Esophagus Stomach Duodenum Mucous layer Stomach cells Microscope Appearance Figure by MIT OCW. Figure by MIT OCW. Figure by MIT OCW....
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l22_case_sdy_omp - 20.201 Lecture 22 Page 4 H Pylori...

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