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‫ﺍﻟﺠﻬﺎﺯﺍﻟﻬﻀﻤﻲ‪ :‬ﻋﻼﺝ ﺍﻟﻘﺮﺣﺔ ﺍﻟﻬﻀﻤﻴﺔ‬ ‫ﺍﻟﻜﻴﻤﻴﺎءﺍﻟﻄﺒﻴﺔ ‪III‬‬

‫ﺍﻟﻔﺼﻞ‪:3‬‬
‫ﺍﻟﻌﻮﺍﻣﻞﺍﻟﻤﺴﺘﺨﺪﻣﺔ ﻓﻲ ﻋﻼﺝ ﺍﻟﻘﺮﺣﺔ ﺍﻟﻬﻀﻤﻴﺔ‬
‫ﻓﺎﺭﻡ‪ .‬ﺗﺸﻴﻢ‪ .‬ﺩﻛﺘﻮﺭﺍﻩ‪.‬‬ ‫ﺳﺎﻡﺩﻭﺑﺎﻭ‬

‫ﺃﻧﺎ‪ .‬ﻣﻌﺮﻓﺘﻲ‬

‫ﺃ‪.‬ﻓﺴﻴﻮﻟﻮﺟﻴﺎ ﺇﻧﺘﺎﺝ ﺍﻟﺤﻤﺾ‬

‫ﻋﺼﻴﺮﺍﻟﻤﻌﺪﺓ ﻋﺒﺎﺭﺓ ﻋﻦ ﻣﺤﻠﻮﻝ ﻣﺘﺴﺎﻭﻱ ﺍﻟﺘﻮﺗﺮ ﻟﺤﻤﺾ ﺍﻟﻬﻴﺪﺭﻭﻛﻠﻮﺭﻳﻚ ﻋﻨﺪ ﺩﺭﺟﺔ ﺣﻤﻮﺿﺔ ‪-0.5‬‬

‫‪، 1.5‬ﺗﺤﺘﻮﻱ ﻋﻠﻰ ﺇﻧﺰﻳﻤﺎﺕ ﻫﻀﻤﻴﺔ ﻭﻣﺨﺎﻁ ﻭﻋﺎﻣﻞ ﺟﻮﻫﺮﻱ ﺿﺮﻭﺭﻱ ﻻﻣﺘﺼﺎﺹ‬
‫ﻓﻴﺘﺎﻣﻴﻦﺏ‪ .12‬ﻓﻲ ﺍﻟﻤﺘﻮﺳﻂ ‪ ،‬ﺗﻔﺮﺯ ﺍﻟﻤﻌﺪﺓ ‪ 3-2‬ﻟﺘﺮﺍﺕ ﻣﻦ ﻋﺼﻴﺮ ﺍﻟﻤﻌﺪﺓ ﻳﻮﻣﻴﺎً‪ .‬ﻳﻌﺰﺯ‬
‫ﺣﻤﺾﺍﻟﻬﻴﺪﺭﻭﻛﻠﻮﺭﻳﻚ ﺩﻭﺭ ﺗﻤﺴﺦ ﺍﻟﺒﺮﻭﺗﻴﻦ ﻓﻲ ﺍﻹﻧﺰﻳﻤﺎﺕ ﺍﻟﻬﺎﺿﻤﺔ ‪ ،‬ﻭﺑﺎﻟﺘﺎﻟﻲ ‪ ،‬ﻳﺴﻬﻞ‬
‫ﺍﻻﻧﻬﻴﺎﺭﺍﻷﻧﺰﻳﻤﻲ ﻟﺒﺮﻭﺗﻴﻨﺎﺕ ﺍﻟﻄﻌﺎﻡ‪ .‬ﻳﻨﺸﻂ ﺍﻟﺤﻤﺾ ﺃﻳﻀﺎً ﺇﻧﺰﻳﻤﺎﺕ ﺍﻟﻤﻌﺪﺓ ﺍﻟﻤﻨﺎﺳﺒﺔ‬
‫ﻭﻳﺤﻮﻝﺍﻟﺒﺒﺴﻴﻨﻮﺟﻴﻨﺎﺕ ﺍﻟﺨﺎﻣﻠﺔ ﺇﻟﻰ ﺍﻟﺒﻴﺒﺴﻴﻦ ﺍﻟﻨﺸﻂ‪ .‬ﺑﺎﻹﺿﺎﻓﺔ ﺇﻟﻰ ﺫﻟﻚ ‪ ،‬ﻳﺘﻢ ﻗﺘﻞ‬
‫ﺍﻟﺒﻜﺘﻴﺮﻳﺎﺍﻟﺘﻲ ﻳﺘﻢ ﺗﻨﺎﻭﻟﻬﺎ ﻋﻦ ﻃﺮﻳﻖ ﺍﻟﻄﻌﺎﻡ ﺃﻳﻀﺎً ﺑﻮﺍﺳﻄﺔ ﺣﻤﺾ ﺍﻟﻬﻴﺪﺭﻭﻛﻠﻮﺭﻳﻚ‪.‬‬

‫ﻳﺘﻢﺇﻧﺘﺎﺝ ﺣﻤﺾ ﺍﻟﻬﻴﺪﺭﻭﻛﻠﻮﺭﻳﻚ ﻋﻦ ﻃﺮﻳﻖ ﺍﻟﺨﻼﻳﺎ ﺍﻟﺠﺪﺍﺭﻳﺔ ﻓﻲ ﺍﻟﻤﻌﺪﺓ‪.‬‬ ‫•‬

‫ﻧﻘﻞ‪+H‬ﻭ ‪-Cl‬ﺗﺤﺪﺙ ﺍﻷﻳﻮﻧﺎﺕ ﺇﻟﻰ ﺍﻟﺘﺠﻮﻳﻒ ﻭﻓﻘﺎً ﻵﻟﻴﺔ ﺍﻟﻨﻘﻞ ﺍﻟﻨﺸﻄﺔ )ﻳﺘﻢ ﺗﻮﻓﻴﺮ‬ ‫•‬
‫ﺍﻟﻄﺎﻗﺔﺑﻮﺍﺳﻄﺔ ‪.(ATP‬‬
‫‪+‬‬‫ﻳﺘﻢﺗﺤﻔﻴﺰ ﻫﺬﺍ ﺍﻟﻨﻘﻞ ﺑﻮﺍﺳﻄﺔ ﺍﻟﺒﺮﻭﺗﻮﻥ ﻭﺍﻟﺒﻮﺗﺎﺳﻴﻮﻡ ‪/+ATPase )H /‬ﻙ‬ ‫•‬
‫‪- ATPase(.‬‬
‫ﺃﻧﺎ‪.‬ﻳﻌﻤﻞ ‪+H‬ﻳﺘﻜﻮﻥ ﻓﻲ ﺍﻟﺨﻼﻳﺎ ﺍﻟﺠﺪﺍﺭﻳﺔ ﻋﻦ ﻃﺮﻳﻖ ﺍﻟﺠﻤﻊ ﺑﻴﻦ ﺍﻟﻤﺎء ﻭﺛﺎﻧﻲ ﺃﻛﺴﻴﺪ‬
‫ﺍﻟﻜﺮﺑﻮﻥﺑﻮﺍﺳﻄﺔ ﺇﻧﺰﻳﻢ ﺍﻟﻜﺮﺑﻮﻧﻴﻚ ﺃﻧﻬﻴﺪﺭﺍﺯ ﻳﺘﻢ ﺇﻟﻘﺎﺅﻩ ﻓﻲ ﺍﻟﺘﺠﻮﻳﻒ ﻋﻦ‬
‫ﻃﺮﻳﻖﺍﻟﻨﻘﻞ ﺍﻟﻨﺸﻂ ‪ ،‬ﺑﻴﻨﻤﺎ ﻳﺘﻢ ﻃﺮﺡ ‪+K‬ﻣﺄﺧﻮﺫ ﻣﻦ ﺍﻟﻠﻮﻣﻦ ﻓﻲ ﺍﻟﻤﻘﺎﺑﻞ ‪،‬‬
‫ﻓﻲﻭﻗﺖ ﻭﺍﺣﺪ‪.‬‬
‫ﺛﺎﻧﻴﺎ‪.‬ﺗﺆﺧﺬ ﺃﻳﻮﻧﺎﺕ ﺍﻟﻜﻠﻮﺭﻳﺪ ﺇﻟﻰ ﺍﻟﺨﻠﻴﺔ ﺍﻟﺠﺪﺍﺭﻳﺔ ﻣﻦ ﺍﻷﻣﻌﺎء‬
‫‪3‬ﻳﺘﻢ ﺗﻮﻓﻴﺮ ﺃﻳﻮﻥ ﻓﻲ ﺍﻷﻣﻌﺎء‬ ‫‪-‬‬ ‫ﺍﻟﺴﺎﺉﻞ ‪،‬ﻭﻓﻲ ﺍﻟﻤﻘﺎﺑﻞ ‪HCO ،‬‬
‫ﺳﺎﺉﻞ‪.‬ﺗﻔﺮﺯ ﺃﻳﻮﻧﺎﺕ ﺍﻟﻜﻠﻮﺭﻳﺪ ﺃﻳﻀﺎً ﻣﻦ ﺍﻟﺨﻠﻴﺔ ﺍﻟﺠﺪﺍﺭﻳﺔ ﺇﻟﻰ ﺍﻟﺘﺠﻮﻳﻒ ﻋﻦ‬
‫ﻃﺮﻳﻖﺍﻟﻨﻘﻞ ﺍﻟﻨﺸﻂ‪.‬‬
‫ﻳﺤﺘﻮﻱﺇﻓﺮﺍﺯ ﺣﻤﺾ ﺍﻟﻤﻌﺪﺓ ﻋﻠﻰ ‪ 150‬ﻣﻠﻲ ﻣﻮﻝ ‪ + H‬ﻭ ‪ -Cl‬ﻟﻜﻞ ﻟﺘﺮ‪.‬‬ ‫•‬
‫ﺗﺰﻳﺪﺍﻟﻤﺮﻛﺒﺎﺕ ﺍﻟﻌﺼﺒﻴﺔ ﻣﺜﻞ ﺍﻷﺳﻴﺘﻴﻞ ﻛﻮﻟﻴﻦ ﻭﺍﻟﻬﺴﺘﺎﻣﻴﻦ ﻭﺍﻟﺠﺎﺳﺘﺮﻳﻦ ﻣﻦ‬ ‫•‬
‫ﺇﻓﺮﺍﺯﺣﻤﺾ ﺍﻟﻬﻴﺪﺭﻭﻛﻠﻮﺭﻳﻚ‪ .‬ﺗﺘﻔﺎﻋﻞ ﻫﺬﻩ ﺍﻟﻤﺮﻛﺒﺎﺕ ﻣﻊ ﻣﺴﺘﻘﺒﻼﺕ ﻣﺤﺪﺩﺓ ﻋﻠﻰ‬
‫ﻏﺸﺎءﺍﻟﺨﻠﻴﺔ‪:‬‬
‫ﺃﻧﺎ‪.‬ﺃﺳﻴﺘﻴﻞ ﻛﻮﻟﻴﻦ ﻣﻊ ﻣﺴﺘﻘﺒﻼﺕ ﺍﻟﻤﺴﻜﺎﺭﻳﻦ‬
‫ﺛﺎﻧﻴﺎ‪.‬ﺍﻟﻬﺴﺘﺎﻣﻴﻦ ﻣﻊ ‪2.H‬ﻣﺴﺘﻘﺒﻼﺕ‬
‫ﺛﺎﻟﺜﺎ‪.‬ﻏﺎﺳﺘﺮﻳﻦ ﻣﻊ ﻛﻮﻟﻴﺴﻴﺴﺘﻮﻛﻴﻨﻴﻦ ‪) CCK-B‬ﺃﻭ ‪ (2CCK‬ﺍﻟﻤﺴﺘﻘﺒﻼﺕ‬

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 ‫ﺍﻟﺠﻬﺎﺯﺍﻟﻬﻀﻤﻲ‪ :‬ﻋﻼﺝ ﺍﻟﻘﺮﺣﺔ ﺍﻟﻬﻀﻤﻴﺔ‬ ‫ﺍﻟﻜﻴﻤﻴﺎءﺍﻟﻄﺒﻴﺔ ‪III‬‬

‫ﺃﻧﻮﺍﻉﻗﺮﺡ ﺍﻟﺠﻬﺎﺯ ﺍﻟﻬﻀﻤﻲ‬

‫‪.1‬ﺍﻟﻘﺮﺣﺔ ﺍﻟﻘﻼﻋﻴﺔ‪ :‬ﻭﻫﻲ ﻗﺮﺣﺔ ﺻﻐﻴﺮﺓ ﺗﺤﺪﺙ ﻣﻨﻔﺮﺩﺓ ﺃﻭ ﻓﻲ ﻣﺠﻤﻮﻋﺎﺕ ﻓﻲ ﺍﻟﻔﻢ ﻋﻠﻰ ﺷﻜﻞ ﺑﻘﻊ ﺑﻴﻀﺎء ﺃﻭ‬
‫ﺣﻤﺮﺍء‪.‬‬

‫‪.2‬ﺍﻟﻘﺮﺣﺔ ﺍﻟﻬﻀﻤﻴﺔ‪:‬ﺧﺮﻕ ﻓﻲ ﺍﻟﻐﺸﺎء ﺍﻟﻤﺨﺎﻃﻲ ﻟﻠﺠﻬﺎﺯ ﺍﻟﻬﻀﻤﻲ‪ .‬ﺍﻷﻧﻮﺍﻉ ﻫﻲ‪:‬‬

‫ﺃ(ﻗﺮﺣﺔ ﺍﻟﻤﻌﺪﺓ‪:‬ﻳﺤﺪﺙ ﻓﻲ ﺍﻟﻤﻌﺪﺓ ﺑﺴﺒﺐ ﺗﺄﺛﻴﺮ ﺍﻟﺤﻤﺾ ﻭﺍﻟﺒﻴﺒﺴﻴﻦ ﻭﺍﻟﺼﻔﺮﺍء ﻋﻠﻰ ﺑﻄﺎﻧﺔ ﺍﻟﻤﻌﺪﺓ )ﺍﻟﻐﺸﺎء ﺍﻟﻤﺨﺎﻃﻲ(‪.‬‬

‫ﺏ( ﻗﺮﺣﺔ ﺍﻻﺛﻨﻲ ﻋﺸﺮ‪:‬ﻳﺤﺪﺙ ﻓﻲ ﺍﻻﺛﻨﻲ ﻋﺸﺮ ‪ ،‬ﺑﺴﺒﺐ ﻋﻤﻞ ﺍﻟﺤﻤﺾ ﻭﺍﻟﺒﻴﺒﺴﻴﻦ ﻋﻠﻰ ﺍﻟﻐﺸﺎء ﺍﻟﻤﺨﺎﻃﻲ ﻓﻲ ﺍﻻﺛﻨﻲ‬
‫ﻋﺸﺮ‪.‬‬
‫‪.3‬ﺁﺣﺮﻭﻥ‪:‬ﻗﺮﺣﺔ ﺍﻟﺼﻘﺮ ﻛﻤﺎ ﻓﻲ ﻣﺘﻼﺯﻣﺔ ﺯﻭﻟﻴﻨﺠﺮ ﺇﻟﻴﺴﻮﻥ‪.‬‬

‫ﺍﻟﻌﻮﺍﻣﻞﺍﻟﻤﺴﺒﺒﺔ ﻟﻘﺮﺣﺔ ﺍﻟﻤﻌﺪﺓ‬

‫‪ ↑.3‬ﺇﻓﺮﺍﺯ ﺣﻤﺾ ﺍﻟﻬﻴﺪﺭﻭﻛﻠﻮﺭﻳﻚ‪.‬‬ ‫ﺩﻭﺍء‬ ‫‪.1‬ﺍﺳﺘﺨﺪﺍﻡ ﻣﻀﺎﺩﺍﺕ ﺍﻻﻟﺘﻬﺎﺏ‬
‫‪ ↓.4‬ﺩﻓﺎﻉ ﻣﺨﺎﻃﻲ ﺿﺪ ﺣﻤﺾ ﺍﻟﻤﻌﺪﺓ‪.‬‬ ‫ﺍﻟﻼﺳﺘﻴﺮﻭﻳﺪﻳﺔ)‪.(NAIDs‬‬
‫‪.2‬ﺍﻹﺻﺎﺑﺔ ﺑﻌﺪﻭﻯ ﻫﻴﻠﻴﻜﻮﺑﺎﻛﺘﺮ ﺑﻴﻠﻮﺭﻱ )‪.(H. pylori‬‬

‫ﺩ‪-‬ﻃﺮﻕ ﻋﻼﺝ ﺍﻟﻘﺮﺣﺔ ﺍﻟﻬﻀﻤﻴﺔ‬

‫‪.3‬ﺣﻤﺎﻳﺔ ﺍﻟﻐﺸﺎء ﺍﻟﻤﺨﺎﻃﻲ ﻓﻲ ﺍﻟﻤﻌﺪﺓ ﻣﻦ ﺍﻟﺘﻠﻒ ‪،‬‬ ‫‪.1‬ﺍﻟﻘﻀﺎء ﻋﻠﻰ ﻋﺪﻭﻯ ﺍﻟﻤﻠﻮﻳﺔ ﺍﻟﺒﻮﺍﺑﻴﺔ‪.‬‬
‫ﺃﻱﺑﺎﺳﺘﺨﺪﺍﻡ ﻋﻮﺍﻣﻞ ﺣﻤﺎﻳﺔ ﺍﻟﺨﻼﻳﺎ ﻣﺜﻞ‬ ‫‪.2‬ﺗﻘﻠﻴﻞ ﺇﻓﺮﺍﺯ ﺣﻤﺾ ﺍﻟﻬﻴﺪﺭﻭﻛﻠﻮﺭﻳﻚ ﺑﺎﺳﺘﺨﺪﺍﻡ‬
‫ﺍﻟﻤﻴﺰﻭﺑﺮﻭﺳﺘﻮﻝﻭﺍﻟﺴﻮﻛﺮﺍﻟﻔﺎﺕ‪.‬‬ ‫ﻣﻀﺎﺩﺍﺕﻣﺴﺘﻘﺒﻼﺕ ‪) H2‬ﻣﺴﺘﻘﺒﻼﺕ‬
‫ﺍﻟﻬﻴﺴﺘﺎﻣﻴﻦﻣﻦ ﺍﻟﻨﻮﻉ ‪ (2‬ﺃﻭ ﻣﺜﺒﻄﺎﺕ ﻣﻀﺨﺔ‬
‫ﺍﻟﺒﺮﻭﺗﻮﻥﺃﻭ ﻏﻴﺮﻫﺎ‪.‬‬

‫ﺍﻟﺸﻜﻞ‪ .1‬ﺗﺄﺛﻴﺮﺍﺕ ﺍﻷﺳﻴﺘﻴﻞ ﻛﻮﻟﻴﻦ ﻭﺍﻟﻬﻴﺴﺘﺎﻣﻴﻦ ﻭﺍﻟﺒﺮﻭﺳﺘﺎﺟﻼﻧﺪﻳﻦ ‪ E2‬ﻭﺍﻟﺠﺎﺳﺘﺮﻳﻦ ﻋﻠﻰ ﺇﻓﺮﺍﺯ ﺣﻤﺾ ﺍﻟﻤﻌﺪﺓ ﺑﻮﺍﺳﻄﺔ ﺍﻟﺨﻼﻳﺎ‬
‫ﺍﻟﺠﺪﺍﺭﻳﺔﻟﻠﻤﻌﺪﺓ‪ Gs .‬ﻭ ‪ Gi‬ﻋﺒﺎﺭﺓ ﻋﻦ ﺑﺮﻭﺗﻴﻨﺎﺕ ﻏﺸﺎﺉﻴﺔ ﺗﺘﻮﺳﻂ ﺍﻟﺘﺄﺛﻴﺮ ﺍﻟﺘﺤﻔﻴﺰﻱ ﺃﻭ ﺍﻟﻤﺜﺒﻂ ﻻﻗﺘﺮﺍﻥ ﺍﻟﻤﺴﺘﻘﺒﻼﺕ ﺇﻟﻰ ‪cyclase‬‬
‫‪.adenylyl‬‬

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 ‫ﺍﻟﺠﻬﺎﺯﺍﻟﻬﻀﻤﻲ‪ :‬ﻋﻼﺝ ﺍﻟﻘﺮﺣﺔ ﺍﻟﻬﻀﻤﻴﺔ‬ ‫ﺍﻟﻜﻴﻤﻴﺎءﺍﻟﻄﺒﻴﺔ ‪III‬‬

‫ﺛﺎﻧﻴﺎً‪.‬ﺗﺼﻨﻴﻒ ﺍﻟﻌﻮﺍﻣﻞ ﺍﻟﻤﺴﺘﺨﺪﻣﺔ ﻓﻲ ﻋﻼﺝ ﺍﻟﻘﺮﺣﺔ ﺍﻟﻬﻀﻤﻴﺔ‬

‫ﺃ‪-‬ﻋﻮﺍﻣﻞ ﺍﻟﺤﺪ ﻣﻦ ﺇﻓﺮﺍﺯ ﺍﻟﺤﻤﺾ‬

‫‪.1‬ﺍﻟﻬﺴﺘﺎﻣﻴﻦ ﺡ‪ -2‬ﺣﺎﺻﺮﺍﺕ ﺍﻟﻤﺴﺘﻘﺒﻼﺕ‬

‫ﻟﻬﺎﺗﺮﻛﻴﺐ ﻛﻴﻤﻴﺎﺉﻲ ﻣﺸﺎﺑﻪ ﻟﻠﻬﻴﺴﺘﺎﻣﻴﻦ ﻭﺗﺤﺘﻮﻱ ﻋﻠﻰ ﺳﻠﺴﻠﺔ‬ ‫•‬

‫ﺟﺎﻧﺒﻴﺔﻃﻮﻳﻠﺔ ﻣﺘﺼﻠﺔ ﺑﻤﺠﻤﻮﻋﺔ ﺇﻳﻤﻴﺪﺍﺯﻭﻝ ‪ ،‬ﻭﺑﺎﻟﺘﺎﻟﻲ ﻓﻬﻲ ﻣﻨﺎﻫﻀﺔ‬
‫ﺗﻨﺎﻓﺴﻴﺔﻟﻠﻬﺴﺘﺎﻣﻴﻦ ﻋﻠﻰ ‪-2H‬ﺍﻟﻤﺴﺘﻘﺒﻼﺕ‪.‬‬

‫ﺃﻫﻢﺁﺛﺎﺭ ‪2H‬ﺣﺎﺻﺮﺍﺕ ﺍﻟﻤﺴﺘﻘﺒﻼﺕ ﻫﻲ ﺃﻧﻬﺎ ﺗﻤﻨﻊ ﺑﻘﻮﺓ ﺗﺄﺛﻴﺮ‬ ‫•‬

‫ﺍﻟﻬﻴﺴﺘﺎﻣﻴﻦﺍﻟﺬﻱ ﻳﺤﻔﺰ ﺇﻓﺮﺍﺯ ﺍﻟﺤﻤﺾ ﻓﻲ ﺍﻟﻤﻌﺪﺓ‪.‬‬

‫ﻣﻘﺎﺭﻧﺔﺑﺎﻷﺩﻭﻳﺔ ﺍﻟﺤﺎﻟﺔ ﻟﻠﺒﺎﺭﺍﺳﻤﺒﺜﻮﻟﻴﺘﻴﻚ ‪2H ،‬ﺣﺎﺻﺮﺍﺕ‬ ‫•‬

‫ﺍﻟﻤﺴﺘﻘﺒﻼﺕﻫﻲ ﻣﻀﺎﺩﺍﺕ ﺣﻤﻮﺿﺔ ﺃﻛﺜﺮ ﻓﻌﺎﻟﻴﺔ‪.‬‬
‫ﻛﻤﺎﺃﻧﻬﺎ ﺗﻘﻠﻞ ﻣﻦ ﻛﻤﻴﺔ ﺍﻟﻌﺎﻣﻞ ﺍﻟﺪﺍﺧﻠﻲ ﺍﻟﺬﻱ ﺗﻔﺮﺯﻩ ﺍﻟﺨﻼﻳﺎ ﺍﻟﺠﺪﺍﺭﻳﺔ‬ ‫•‬
‫→ ﺍﻟﺘﻲ ﺗﺴﺒﺐ ﻓﻴﺘﺎﻣﻴﻦ ﺏ‪12‬ﻧﻘﺺ ﻣﻊ ﻫﺬﻩ ﺍﻷﺩﻭﻳﺔ‪.‬‬

‫ﻭﻣﻦﺍﻟﻤﻌﺮﻭﻑ ﺃﻳﻀﺎً ﺃﻧﻬﺎ ﺗﻤﻨﻊ ﺇﻓﺮﺍﺯ ﺍﻟﺒﻴﺒﺴﻴﻦ ﻓﻲ ﺍﻟﺒﺸﺮ‪.‬‬ ‫•‬

‫ﺳﺎﺭ ﻳﺘﻢ ﻓﺤﺼﻬﺎ ﻓﻲ ﺛﻼﺛﺔ ﺃﺟﺰﺍء‪:‬‬ ‫•‬

‫ﺣﻠﻘﺔﺍﻟﻌﻄﺮﻳﺔ‪:‬ﺗﻢ ﺍﺧﺘﻴﺎﺭ ﺣﻠﻘﺔ ﺍﻹﻳﻤﻴﺪﺍﺯﻭﻝ ﻓﻲ ﺑﻨﻴﺔ ﺍﻟﻬﻴﺴﺘﺎﻣﻴﻦ ﺑﺎﻋﺘﺒﺎﺭﻫﺎ ﺍﻟﻬﻴﻜﻞ ﺍﻟﺮﺉﻴﺴﻲ ﻓﻲ ﺃﻭﻝ ‪H‬‬ ‫ﺃﻧﺎ‪.‬‬
‫‪2.‬ﺳﻴﻤﻴﺘﻴﺪﻳﻦ ﻣﺎﻧﻊ ﻣﺴﺘﻘﺒﻼﺕ‪ .‬ﻣﻊ ﺇﺩﺧﺎﻝ ﺑﺪﻳﻞ ﺍﻟﻤﻴﺜﻴﻞ ﻓﻲ ﺍﻟﻤﻮﺿﻊ ﺍﻟﺨﺎﻣﺲ ‪ ،‬ﻳﺰﺩﺍﺩ ﺍﻟﻨﺸﺎﻁ‪.‬‬
‫ﺍﻟﺤﻠﻘﺎﺕﻏﻴﺮ ﺍﻟﻤﺘﺠﺎﻧﺴﺔ ‪ ،‬ﻭﻫﻲ ﻋﺒﺎﺭﺓ ﻋﻦ ﺍﻳﺰﻭﺳﺘﻴﺮ ﻓﻲ ﺣﻠﻘﺔ ﺇﻳﻤﻴﺪﺍﺯﻭﻝ ‪ ،‬ﻋﻠﻰ ﺳﺒﻴﻞ ﺍﻟﻤﺜﺎﻝ ‪ ،‬ﺣﻠﻘﺔ‬
‫ﺛﻴﺎﺯﻭﻝ ‪،‬ﺗﻈﻬﺮ ﺃﻳﻀﺎً ﻧﻔﺲ ﺍﻟﻨﺸﺎﻁ‪.‬‬
‫ﺍﻟﺴﻠﺴﻠﺔﺍﻟﻮﺳﻴﻄﺔ‪:‬ﻳﻤﻜﻦ ﺃﻥ ﻳﻜﻮﻥ ﺍﻟﺠﺰء ﺍﻟﺬﻱ ﻳﺸﻴﺮ ﺇﻟﻴﻪ ‪ X‬ﻓﻲ ﺍﻟﺴﻠﺴﻠﺔ ﺍﻟﻮﺳﻴﻄﺔ –‪ -2CH‬ﺃﻭ ‪ -O-‬ﺃﻭ‬ ‫ﺛﺎﻧﻴﺎ‪.‬‬

‫‪ .-S-‬ﺍﻟﻤﺴﺎﻓﺔ ﺑﻴﻦ ﺃﺭﺑﻊ ﺫﺭﺍﺕ ﻛﺮﺑﻮﻥ ﺑﻴﻦ ﺍﻟﺒﻨﻴﺔ ﺍﻟﻌﻄﺮﻳﺔ ﻭﺑﻨﻴﺔ ﺍﻷﻣﻴﺪ ﺍﻷﺳﺎﺳﻴﺔ ﻣﻄﻠﻮﺑﺔ ﻟﻠﻨﺸﺎﻁ‪.‬‬
‫ﺳﻠﺴﻠﺔﺃﻗﺼﺮ → ↓ ﺍﻟﻨﺸﺎﻁ‪ .‬ﻣﺠﻤﻮﻋﺔ (‪Thioether )-S-‬‬
‫→ ↑ ﺍﻟﻨﺸﺎﻁ‪.‬‬
‫ﺳﻠﺴﻠﺔﺟﺎﻧﺒﻴﺔ ﺫﺍﺕ ﻃﺎﺑﻊ ﺃﺳﺎﺳﻲ‪:‬ﻳﻤﻜﻦ ﺃﻥ ﺗﻜﻮﻥ ﻫﺬﻩ ﺍﻟﻤﺠﻤﻮﻋﺔ ﻏﻮﺍﻧﻴﻞ ‪ ،‬ﺛﻴﻮﺭﻳﺎ ﻭﻣﺸﺘﻘﺎﺕ ﺗﺤﻤﻞ‬ ‫ﺛﺎﻟﺜﺎ‪.‬‬

‫ﺑﺪﺍﺉﻞ‪.‬ﻷﻗﺼﻰ ﻧﺸﺎﻁ ‪ ،‬ﻳﺠﺐ ﺃﻥ ﻳﻜﻮﻥ ‪ .pKa 0.9-0.4‬ﻣﺘﻘﺒﻞ ﺍﻹﻟﻜﺘﺮﻭﻥ‬

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 ‫ﺍﻟﺠﻬﺎﺯﺍﻟﻬﻀﻤﻲ‪ :‬ﻋﻼﺝ ﺍﻟﻘﺮﺣﺔ ﺍﻟﻬﻀﻤﻴﺔ‬ ‫ﺍﻟﻜﻴﻤﻴﺎءﺍﻟﻄﺒﻴﺔ ‪III‬‬

‫ﻣﺠﻤﻮﻋﺎﺕﻣﺜﻞ ‪ cyano‬ﻭ ‪ nitro‬ﻭ ‪ ، sulfamoyl‬ﺍﻟﺘﻲ ﺳﺘﻮﻓﺮ ﺫﻟﻚ ‪ ،‬ﻣﻔﻀﻠﺔ ﻛﺒﺪﺍﺉﻞ‪.‬‬

‫ﺃ( ﺳﻴﻤﻴﺘﻴﺪﻳﻦ‬
‫‪N-Cyano-N'-methyl-N '- )2 - )))5-methyl-1H-imidazol-4-yl( methyl( thio( ethyl( guanidine‬‬ ‫•‬
‫ﺇﻧﻪﻣﺰﻋﺞ ﻗﻠﻴﻼ ًﻓﻲ ﺍﻟﻤﺎء‪ .‬ﺗﺰﺩﺍﺩ ﻗﺎﺑﻠﻴﺔ ﺍﻟﺬﻭﺑﺎﻥ ﻓﻲ ﺍﻟﺤﻤﺾ ﺍﻟﻤﺨﻔﻒ ﺍﻟﺬﻱ ﻳﻘﻮﻡ ﺑﺒﺮﻭﺗﻮﻧﺎﺕ ﺣﻠﻘﺔ‬ ‫•‬
‫ﺍﻹﻳﻤﻴﺪﺍﺯﻭﻝ‪.‬‬
‫ﺍﻟﺴﻴﻤﻴﺘﻴﺪﻳﻦﻳﺜﺒﻂ ﺇﻧﺰﻳﻤﺎﺕ ‪ ↓ → CYP‬ﺍﺳﺘﻘﻼﺏ ﺍﻷﺩﻭﻳﺔ ﺍﻟﺘﻲ ﺗﺸﻜﻞ ﺭﻛﺎﺉﺰ ‪CYP‬‬ ‫•‬
‫ﻋﻠﻰﺳﺒﻴﻞ ﺍﻟﻤﺜﺎﻝ ‪ ،‬ﺍﻟﻔﻴﻨﻴﺘﻮﻳﻦ ‪ ،‬ﺑﺮﻭﺑﺮﺍﻧﻮﻟﻮﻝ ‪ ،‬ﻧﻴﻔﻴﺪﻳﺒﻴﻦ ‪ ،‬ﺍﻟﺒﻨﺰﻭﺩﻳﺎﺯﻳﺒﻴﻨﺎﺕ ‪ ،‬ﺑﻌﺾ ﻣﻀﺎﺩﺍﺕ ﺍﻻﻛﺘﺉﺎﺏ ﺛﻼﺛﻴﺔ‬

‫ﺍﻟﺤﻠﻘﺎﺕ ‪،‬ﻟﻴﺪﻭﻛﺎﺉﻴﻦ ‪ ،‬ﺛﻴﻮﻓﻴﻠﻴﻦ ‪ ،‬ﻣﻴﺘﺮﻭﻧﻴﺪﺍﺯﻭﻝ ‪ ،‬ﻭﻣﻀﺎﺩﺍﺕ ﺍﻟﺘﺨﺜﺮ ﻣﻦ ﻧﻮﻉ ﺍﻟﻮﺍﺭﻓﺎﺭﻳﻦ‪.‬‬

‫ﺳﻴﻤﻴﺘﻴﺪﻳﻦ↓ ﺣﻤﻮﺿﺔ ﺍﻟﻤﻌﺪﺓ ﺍﻣﺘﺼﺎﺹ ﻣﻀﺎﺩﺍﺕ ﺍﻟﻔﻄﺮﻳﺎﺕ ﺍﻵﺯﻭﻝ )ﻣﺜﻞ ﺍﻟﻜﻴﺘﻮﻛﻮﻧﺎﺯﻭﻝ( ﻭﺍﻷﺩﻭﻳﺔ‬ ‫•‬
‫ﺍﻷﺧﺮﻯﺍﻟﺘﻲ ﺗﺘﻄﻠﺐ ﺑﻴﺉﺔ ﺣﻤﻀﻴﺔ ﻟﻠﺘﺤﻠﻞ‪) .‬ﺍﻟﺤﻞ‪ :‬ﺳﺎﻋﺘﺎﻥ ﺑﻴﻦ ﺍﻟﺴﻴﻤﻴﺘﻴﺪﻳﻦ ﻭﺍﻷﺩﻭﻳﺔ ﺍﻷﺧﺮﻯ(‬

‫ﺍﻟﺘﺄﺛﻴﺮﺍﺕﺍﻟﻀﺎﺉﺮﺓ ﺍﻟﺸﻬﻴﺮﺓ‪ :‬ﺍﻟﺘﺜﺪﻱ ‪ ،‬ﻭﺍﻟﻌﺠﺰ ﺍﻟﺠﻨﺴﻲ ‪ ،‬ﻭﺛﺮ ﺍﻟﻠﺒﻦ‪.‬‬ ‫•‬

‫ﺃﺷﻜﺎﻝﺍﻟﺠﺮﻋﺎﺕ‪ :‬ﺃﻗﺮﺍﺹ )‪ 800 ، 400 ، 300 ، 200‬ﻣﺠﻢ( ‪ ،‬ﺳﺎﺉﻞ )‪ 300‬ﻣﺠﻢ ‪ 5 /‬ﻣﻞ( ‪ ،‬ﺣﻘﻦ )‪ / 150‬ﻣﻞ ﻭ ‪6‬‬ ‫•‬
‫ﻣﺠﻢ ‪ /‬ﻣﻞ(‬

‫ﺏ( ﺭﺍﻧﻴﺘﻴﺪﻳﻦ‬
‫• ﻋﻠﻰﻏﺮﺍﺭ ﺍﻟﺴﻴﻤﻴﺘﻴﺪﻳﻦ ‪ ،‬ﻳﺘﺄﺛﺮ ﺍﻣﺘﺼﺎﺻﻪ ﺑﺎﻟﺘﻨﺎﻭﻝ ﺍﻟﻤﺘﺰﺍﻣﻦ ﻣﻊ ﻣﻀﺎﺩﺍﺕ ﺍﻟﺤﻤﻮﺿﺔ ﺍﻷﺧﺮﻯ‬
‫ﻣﻠﺢﺍﻟﻬﻴﺪﺭﻭﻛﻠﻮﺭﻳﺪ ﺍﻟﺨﺎﺹ ﺑﻪ ﻗﺎﺑﻞ ﻟﻠﺬﻭﺑﺎﻥ ﻓﻲ ﺍﻟﻤﺎء ﺑﺪﺭﺟﺔ ﻋﺎﻟﻴﺔ‪.‬‬ ‫•‬
‫ﺇﻧﻪﻣﺜﺒﻂ ﺿﻌﻴﻒ ﻟـ ‪ .CYP‬ﻳﺘﺄﺛﺮ ﺍﻟﻮﺍﺭﻓﺎﺭﻳﻦ ﻭﺍﻟﺘﺮﻳﺎﺯﻭﻻﻡ ﻓﻘﻂ‪.‬‬ ‫•‬
‫ﺃﺷﻜﺎﻝﺍﻟﺠﺮﻋﺎﺕ‪ :‬ﺃﻗﺮﺍﺹ )‪ 300 ، 150 ، 75‬ﻣﻠﺠﻢ ﻣﻦ ﻣﻠﺢ ﺣﻤﺾ ﺍﻟﻬﻴﺪﺭﻭﻛﻠﻮﺭﻳﻚ( ؛ ﺃﻗﺮﺍﺹ ﻓﻮﺍﺭﺓ )‪ 25‬ﻭ ‪ 150‬ﻣﺠﻢ( ؛ ﻛﺒﺴﻮﻻﺕ )‪150‬‬ ‫•‬
‫ﻭ‪ 300‬ﻣﺠﻢ( ؛ ﺷﺮﺍﺏ )‪ 15‬ﻣﺠﻢ ‪ /‬ﻣﻞ ﻛﻤﻠﺢ ﺣﻤﺾ ﺍﻟﻬﻴﺪﺭﻭﻛﻠﻮﺭﻳﻚ( ؛ ﺍﻟﺤﻘﻦ )‪ 1‬ﻭ ‪ 25‬ﻣﺠﻢ ‪ /‬ﻣﻞ ﻋﻠﻰ ﻫﻴﺉﺔ ﻣﻠﺢ ﺣﻤﺾ ﺍﻟﻬﻴﺪﺭﻭﻛﻠﻮﺭﻳﻚ‬

‫(‬

‫ﺝ( ﻓﺎﻣﻮﺗﻴﺪﻳﻦ‬
‫• ﻗﺪﻳﺤﺎﻛﻲ ﺑﺪﻳﻠﻪ ﺍﻟﻐﻮﺍﻧﻴﺪﻳﻦ ﺍﻟﻤﻮﺟﻮﺩ ﻋﻠﻰ ﺣﻠﻘﺔ ﺍﻟﺜﻴﺎﺯﻭﻝ ﺇﻳﻤﻴﺪﺍﺯﻭﻝ ﺍﻟﺴﻴﻤﻴﺘﻴﺪﻳﻦ‬

‫ﺩ( ﻧﻴﺰﺍﺗﻴﺪﻳﻦ‬
‫ﻧﻴﺰﺍﺗﻴﺪﻳﻦ ‪) -2]] - 2] -N،‬ﺛﻨﺎﺉﻲ ﻣﻴﺜﻴﻼﻣﻴﻦ( ﻣﻴﺜﻴﻞ[ ‪-4-‬ﺛﻴﺎﺯﻭﻟﻴﻞ[ ﻣﻴﺜﻴﻞ[ ﺛﻴﻮ[ ‪-‬ﺇﻳﺜﻴﻞ[ ‪ -'N-‬ﻣﻴﺜﻴﻞ‪-‬‬ ‫•‬
‫‪-2‬ﻧﻴﺘﺮﻭ‪-1،1-‬ﺇﻳﺜﻨﺪﻳﺎﻣﻴﻦ‬

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 ‫ﺍﻟﺠﻬﺎﺯﺍﻟﻬﻀﻤﻲ‪ :‬ﻋﻼﺝ ﺍﻟﻘﺮﺣﺔ ﺍﻟﻬﻀﻤﻴﺔ‬ ‫ﺍﻟﻜﻴﻤﻴﺎءﺍﻟﻄﺒﻴﺔ ‪III‬‬

‫ﻭﻫﻮﻣﺸﺘﻖ ﻣﻦ ﺛﻴﺎﺯﻭﻝ ﻣﻦ ﺭﺍﻧﻴﺘﻴﺪﻳﻦ‪ .‬ﺯﺍﺩ ﺍﻻﺳﺘﺒﺪﺍﻝ ﺍﻷﻳﺰﻭﺳﺘﺮﻱ ﺍﻟﺤﻴﻮﻱ ﻟﻠﺜﻴﺎﺯﻭﻝ ﻓﻲ ﺍﻟﻨﻴﺰﺍﺗﻴﺪﻳﻦ ﻣﻦ‬ ‫•‬
‫ﺍﻟﻔﺎﻋﻠﻴﺔ‪.‬‬

‫‪.2‬ﻣﺜﺒﻄﺎﺕ ﻣﻀﺨﺔ ﺍﻟﺒﺮﻭﺗﻮﻥ )‪(PPIs‬‬

‫• ﺁﻟﻴﺔﺍﻟﻌﻤﻞ‪ :‬ﺑﻐﺾ ﺍﻟﻨﻈﺮ ﻋﻦ ﺗﺤﻔﻴﺰ ﺍﻟﻤﺴﺘﻘﺒﻼﺕ )‪2H‬ﺃﻭ ‪ M‬ﺃﻭ ‪ ، (2CCK‬ﻣﺜﺒﻄﺎﺕ ﻣﻀﺨﺔ ﺍﻟﺒﺮﻭﺗﻮﻥ ﺗﻤﻨﻊ ﺇﻓﺮﺍﺯ‬
‫ﺣﻤﺾﺍﻟﻤﻌﺪﺓ‪ .‬ﻣﺜﺒﻄﺎﺕ ﻣﻀﺨﺔ ﺍﻟﺒﺮﻭﺗﻮﻥ ﻫﻲ ﻋﻘﺎﻗﻴﺮ ﺃﻭﻟﻴﺔ ﺗﻌﻴﺪ ﺗﺮﺗﻴﺒﻬﺎ ﻓﻲ ﺍﻟﺒﻴﺉﺔ ﺍﻟﺤﻤﻀﻴﺔ ﻹﻧﺘﺎﺝ‬
‫ﻣﺴﺘﻘﻠﺒﺎﺕ)ﺍﻟﺴﻠﻔﻴﻨﺎﻣﻴﺪﺍﺕ( ﺍﻟﺘﻲ ﺗﺸﻜﻞ ﺭﻭﺍﺑﻂ ﺗﺴﺎﻫﻤﻴﺔ ﻣﻊ ‪/+H‬ﻙ‪.+‬ﺍﻟﺬﻱ ﻳﺘﻢ ﺗﺜﺒﻴﻄﻪ ﻭﺗﻌﻄﻴﻠﻪ ﺑﻌﺪ ﺫﻟﻚ‪.‬‬
‫ﻭﺑﺎﻟﺘﺎﻟﻲﻓﺈﻥ ﻋﻤﻠﻴﺔ ﺍﻟﺘﺜﺒﻴﻂ ﻫﺬﻩ ﻻ ﺭﺟﻌﺔ ﻓﻴﻬﺎ ‪-ATPase‬‬
‫• ﺗﻌﺘﺒﺮﻣﺠﻤﻮﻋﺎﺕ ﺍﻟﺴﻠﻔﻬﻴﺪﺭﻳﻞ )‪(SH-‬‬
‫ﻟﺒﻌﺾﺍﻷﺣﻤﺎﺽ ﺍﻷﻣﻴﻨﻴﺔ ﺍﻟﺴﻴﺴﺘﻴﻦ‬
‫ﻣﻮﺍﻗﻊﻣﺤﺘﻤﻠﺔ ﻟﻌﻤﻞ ﻣﺜﺒﻄﺎﺕ‬
‫ﻣﻀﺨﺔﺍﻟﺒﺮﻭﺗﻮﻥ‪ .‬ﺗﺘﺸﻜﻞ ﺭﻭﺍﺑﻂ ﺛﺎﻧﻲ‬
‫ﻛﺒﺮﻳﺘﻴﺪ)ﺗﺴﺎﻫﻤﻴﺔ( ﺑﻮﺍﺳﻄﺔ ﻣﺸﺘﻖ‬
‫ﺃﻭﻣﻴﺒﺮﺍﺯﻭﻝﺍﻟﻤﻌﺎﺩ ﺗﺮﺗﻴﺒﻪ‪ .‬ﺗﻢ ﺍﻹﺑﻼﻍ‬
‫ﻋﻦﻧﺘﺎﺉﺞ ﻣﺨﺘﻠﻔﺔ ﻗﻠﻴﻼ ًﻋﻦ‬
‫ﻻﻧﺴﻮﺑﺮﺍﺯﻭﻝﻭﺑﺎﻧﺘﻮﺑﺮﺍﺯﻭﻝ ﻭﺭﺍﺑﻴﺒﺮﺍﺯﻭﻝ‪.‬‬

‫ﻧﻜﻮﻥ‬ ‫‪PPIs‬‬ ‫ﺍﻟﺘﻤﺜﻴﻞﺍﻟﻐﺬﺍﺉﻲ‪:‬‬ ‫•‬

‫ﻳﺘﻢﺍﺳﺘﻘﻼﺑﻪ ﻓﻲ ﺍﻟﻤﻘﺎﻡ ﺍﻷﻭﻝ ﻓﻲ‬
‫ﻛﺒﺮﻳﺘﻴﺪ ‪،‬‬ ‫ﺍﻟﻜﺒﺪ‪.‬ﺳﻠﻔﻮﻥ ‪،‬‬

‫ﺍﻟﺸﻜﻞ‪ .2‬ﺍﻟﺘﻨﺸﻴﻂ ﺍﻟﻤﺤﻔﺰ ﺑﺎﻟﺤﻤﺾ ﻣﻦ ﺃﻭﻣﻴﺒﺮﺍﺯﻭﻝ ﺇﻟﻰ ﺍﻟﺴﻠﻔﻴﻨﺎﻣﻴﺪ ﺍﻟﺘﻔﺎﻋﻠﻲ‪ .‬ﻓﻲ ﺍﻟﺨﻠﻴﺔ‬ ‫ﺱ‪-‬‬ ‫ﻭ‬ ‫ﻫﻴﺪﺭﻭﻛﺴﻴﻞ ‪،‬‬
‫ﺍﻟﺠﺪﺍﺭﻳﺔ ‪/+H،‬ﻙ‪.+‬ﺑﻘﺎﻳﺎ ﺍﻟﺴﻴﺴﺘﻴﻦ ‪ ،‬ﻳﺘﻔﺎﻋﻞ ﻟﺘﺸﻜﻴﻞ ﻣﺜﺒﻂ ﺇﻧﺰﻳﻢ ﻣﺮﺗﺒﻂ ﺑﺜﺎﻧﻲ ﻛﺒﺮﻳﺘﻴﺪ ‪-ATPase ،‬‬ ‫ﻟﺪﻳﻚ‬ ‫ﺗﻢﺍﻹﺑﻼﻍ ﻋﻦ ﺍﻟﻤﺴﺘﻘﻠﺒﺎﺕ‬
‫ﻧﻜﻮﻥ‬ ‫ﻣﻨﺰﻭﻋﺔﺍﻟﻤﻴﺜﻴﻞ‪PPIs .‬‬
‫ﺑﻮﺍﺳﻄﺔ‬ ‫ﻳﺘﻢﺍﺳﺘﻘﻼﺑﻪ ﻓﻲ ﺍﻟﻐﺎﻟﺐ‬
‫‪ 2CYP‬ﺝ ‪ ،19‬ﻭﺑﺪﺭﺟﺔ ﺃﻗﻞ ﺑﻮﺍﺳﻄﺔ‬
‫‪.3A4CYP‬‬
‫• ‪2‬ﺝ ‪ 19‬ﺍﻷﻛﺴﺪﺓ ﺗﺤﻮﻝ ﺍﻟﻜﻠﻮﺑﻴﺪﻭﺟﺮﻳﻞ ﺇﻟﻰ ﺷﻜﻠﻪ ﺍﻟﻤﻀﺎﺩ ﻟﻠﺘﺨﺜﺮ‪.‬‬
‫ﺍﻟﻤﻨﺎﻓﺴﺔﻋﻠﻰ ‪ 2PPIs‬ﺝ ‪ ↓ → 19‬ﻧﺸﺎﻁ ﻛﻠﻮﺑﻴﺪﻭﻗﺮﻝ‪.‬‬
‫• ﺍﻟﻤﻌﺪﺓ‪/+H‬ﻙ‪ H+‬ﻟﻪ ﺑﻌﺾ ﺃﻭﺟﻪ ﺍﻟﺘﺸﺎﺑﻪ ﻣﻊ ‪/+-ATPase‬ﻙ‪.+‬ﻓﻲ‬
‫ﻧﺎﻗﻀﺎﺕﺍﻟﻌﻈﻢ ‪ ،‬ﻭﺍﻟﺬﻱ ﻳﺸﺎﺭﻙ ﻓﻲ ﺍﺭﺗﺸﺎﻑ ﺍﻟﻌﻈﺎﻡ ‪- ATPase‬‬

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 ‫ﺍﻟﺠﻬﺎﺯﺍﻟﻬﻀﻤﻲ‪ :‬ﻋﻼﺝ ﺍﻟﻘﺮﺣﺔ ﺍﻟﻬﻀﻤﻴﺔ‬ ‫ﺍﻟﻜﻴﻤﻴﺎءﺍﻟﻄﺒﻴﺔ ‪III‬‬

‫• ﺳﺎﺭ‪:‬‬
‫ﺃﻧﺎ‪.‬ﺟﻤﻴﻊ ﺍﻟﻤﺮﻛﺒﺎﺕ ﻋﺒﺎﺭﺓ ﻋﻦ ﻣﺸﺘﻘﺎﺕ ﻣﻦ ‪ benzimidazole sulfinyl‬ﻭﺍﻟﺘﻲ ﻳﺘﻢ ﺗﺠﺴﻴﺮﻫﺎ ﻋﺒﺮ ﻣﻴﺜﻴﻠﻴﻦ‬
‫ﺇﻟﻰﺣﻠﻘﺔ ﺑﻴﺮﻳﺪﻳﻦ ‪.yl-2‬‬
‫ﺛﺎﻧﻴﺎ‪.‬ﻳﺠﺐ ﺃﻥ ﺗﺘﺮﺍﻛﻢ ﻣﺜﺒﻄﺎﺕ ﻣﻀﺨﺔ ﺍﻟﺒﺮﻭﺗﻮﻥ ﻓﻲ ﺍﻟﺨﻠﻴﺔ ﺍﻟﺠﺪﺍﺭﻳﺔ ﻟﺘﺤﻘﻴﻖ‬
‫ﻧﺸﺎﻃﻬﺎ‪.‬ﻳﺨﻀﻊ ﻫﺬﺍ ﺍﻟﺘﺮﺍﻛﻢ ﻟـ ‪pK‬ﺃﻣﻦ ﻧﻴﺘﺮﻭﺟﻴﻦ ﺑﻴﺮﻳﺪﻳﻦ ﺍﻟﺬﻱ ﻳﺘﺮﺍﻭﺡ‬
‫ﺑﻴﻦ‪.4.5 - 3.8‬‬
‫ﺛﺎﻟﺜﺎ‪.‬ﺑﺮﻭﺗﻮﻥ ﺑﻨﺰﻳﻤﻴﺪﺍﺯﻭﻝ ﻣﻬﻢ ﻓﻲ ﺑﺪﺍﻳﺔ ﻭﻣﺪﺓ ﺍﻟﺘﺄﺛﻴﺮ‪ .‬ﻳﺘﻢ ﺗﺤﺪﻳﺪ ﺗﺤﻮﻳﻞ‬
‫ﻣﺜﺒﻄﺎﺕﻣﻀﺨﺔ ﺍﻟﺒﺮﻭﺗﻮﻥ ﺇﻟﻰ ﺍﻟﺴﻠﻔﻴﻨﺎﻣﻴﺪﺍﺕ ﺍﻟﻨﺸﻄﺔ ﺇﻟﻰ ﺣﺪ ﻛﺒﻴﺮ‬
‫ﺑﻮﺍﺳﻄﺔ‪pK‬ﺃﻣﻦ ﻣﺠﻤﻮﻋﺔ ‪benzimidazole )pK‬ﺃ‪ .(2‬ﺃﻭﻣﻴﺒﺮﺍﺯﻭﻝ ‪،‬‬
‫ﻻﻧﺴﻮﺑﺮﺍﺯﻭﻝ ‪،‬ﻭﺭﺍﺑﻴﺒﺮﺍﺯﻭﻝ ﻣﻊ ﺍﺭﺗﻔﺎﻉ ‪pK‬ﺃ‪ (0.62-0.79) 2‬ﻳﺨﻀﻊ‬
‫ﻟﺒﺮﻭﺗﻮﻥﺑﻨﺰﻳﻤﻴﺪﺍﺯﻭﻝ ﻭﺗﻜﻮﻳﻦ ﺳﻠﻔﻴﻨﺎﻣﻴﺪ ﺃﺳﺮﻉ ﻣﻦ ﺑﺎﻧﺘﻮﺑﺮﺍﺯﻭﻝ ﻣﻊ ‪pK‬‬
‫ﺃ‪ 2‬ﻣﻦ ‪ .0.11‬ﻳﻌﺰﺯ ﻭﺟﻮﺩ ﻣﺠﻤﻮﻋﺎﺕ ﺍﻟﺘﺒﺮﻉ ﺑﺎﻟﻨﺎﺧﺒﻴﻦ ﻋﻠﻰ ﺣﻠﻘﺔ‬
‫ﺍﻟﺒﻨﺰﻳﻤﻴﺪﺍﺯﻭﻝﺍﻟﺒﺮﻭﺗﻮﻧﺎﺕ‪.‬‬

‫ﺭﺍﺑﻌﺎ‪.‬ﺍﻟﻌﻮﺍﻣﻞ ﺍﻷﺧﺮﻯ ﺍﻟﺘﻲ ﺗﺤﺪﺩ ﻣﺪﺓ ﺍﻟﻌﻤﻞ )‪:(DOA‬‬

‫ﺑﻘﺎﻳﺎﺍﻟﺴﻴﺴﺘﻴﻦ )ﺍﻟﻤﺪﻯ ﻭﺍﻟﻄﺒﻴﻌﺔ( ﻋﻠﻰ ﺳﺒﻴﻞ ﺍﻟﻤﺜﺎﻝ ‪،‬‬ ‫▪‬
‫ﺍﻟﺴﻴﺴﺘﻴﻦ‪ 822‬ﻣﻬﻢ ﺑﺴﺒﺐ ﻣﻮﻗﻌﻪ ﻓﻲ ﻣﺠﺎﻝ ﻧﻘﻞ‬
‫ﺍﻟﻤﻀﺨﺔ ‪،‬ﺗﺜﺒﻴﻄﻪ → ↑ ‪ DOA‬ﻣﻦ ﺍﻟﺒﺎﻧﺘﻮﺑﺮﺍﺯﻭﻝ‬

‫ﺩﻭﺭﺍﻥﻣﻀﺨﺔ ﺍﻟﺒﺮﻭﺗﻴﻦ‬ ‫▪‬

‫ﺗﻔﻌﻴﻞﺍﻟﻤﻀﺨﺎﺕ ﺍﻟﺨﺎﻣﻠﺔ‬ ‫▪‬
‫‪ tenatoprazole.‬ﺇﻟﻰ ﺍﻟﻤﺮﻛﺒﺎﺕ ﺍﻟﺘﻲ ﻟﻬﺎ ﻣﺪﺓ ﻋﻤﻞ ﺃﻃﻮﻝ ‪ ،‬ﻣﺜﻞ ‪ N‬ﺑـ ‪ benzimidazole‬ﻣﻦ ‪ C4‬ﻳﺆﺩﻱ‬
‫ﺍﺳﺘﺒﺪﺍﻝ ‪v.‬‬
‫ﺍﻟﺴﺎﺩﺱ‪.‬ﺗﺆﺩﻱ ﺍﻟﺘﻐﻴﻴﺮﺍﺕ )ﺍﻻﺳﺘﺒﺪﺍﻻﺕ ﺃﻭ ﺍﻟﺰﻳﺎﺩﺓ ﻓﻲ ﺍﻟﻄﻮﻝ( ﻓﻲ ﺳﻠﺴﻠﺔ ﻣﻴﺜﻴﻞ ﺳﻠﻔﻴﻨﻴﻞ ﺇﻟﻰ ﺇﻧﺘﺎﺝ ﻣﺮﻛﺒﺎﺕ‬
‫ﺧﺎﻣﻠﺔ‪.‬‬
‫ﺍﻟﺴﺎﺑﻊ‪.‬ﻩ‪-‬ﻣﺠﻤﻮﻋﺎﺕ ﺍﻟﺘﺒﺮﻉ )ﻋﻠﻰ ﺳﺒﻴﻞ ﺍﻟﻤﺜﺎﻝ ‪- ،3CH- ،‬ﺃﻭﻙ‪ (3‬ﻋﻠﻰ ‪ C4‬ﻣﻦ ﺑﻴﺮﻳﺪﻳﻦ ‪ -‬ﺃﻟﻔﺔ ﺍﻟﻨﻮﺍﺓ ﻣﻦ ‪→ N‬‬
‫ﺗﻌﺰﺯﺗﻜﻮﻳﻦ ﺍﻟﺴﻠﻔﻴﻨﺎﻣﻴﺪ ﺍﻟﻨﺸﻂ‪ .‬ﻫﺬﻩ ﻩ‪-‬ﻛﻤﺎ ﺗﺴﺎﻫﻢ ﺍﻟﻤﺠﻤﻮﻋﺎﺕ ﺍﻟﻤﺘﺒﺮﻋﺔ ﻓﻲ ﺍﻻﺳﺘﻘﺮﺍﺭ ﻭﺍﻟﺘﺮﺍﻛﻢ ﻓﻲ‬
‫ﻣﻮﻗﻊﺍﻟﻌﻤﻞ‪ .‬ﻩ‪-‬ﺳﺤﺐ ﺍﻟﻤﺠﻤﻮﻋﺎﺕ )‪ (3، -CF2CN ، -NO-‬ﻳﻤﻜﻦ ﺃﻥ ﻳﺴﺒﺐ ﻓﻘﺪﺍﻥ ﺍﻟﻨﺸﺎﻁ‪.‬‬

‫ﻭﻳﻠﺴﻮﻥﻭﺟﻴﺰﻓﻮﻟﺪ‬

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 ‫ﺍﻟﺠﻬﺎﺯﺍﻟﻬﻀﻤﻲ‪ :‬ﻋﻼﺝ ﺍﻟﻘﺮﺣﺔ ﺍﻟﻬﻀﻤﻴﺔ‬ ‫ﺍﻟﻜﻴﻤﻴﺎءﺍﻟﻄﺒﻴﺔ ‪III‬‬

‫ﺃ( ﺃﻭﻣﻴﺒﺮﺍﺯﻭﻝ‬
‫‪-5‬ﺛﻨﺎﺉﻲ ﻣﻴﺜﻴﻞ‪-2-‬ﺑﻴﺮﻳﺪﻳﻨﻴﻞ( ﻣﻴﺜﻴﻞ(‬ ‫‪-5‬ﻣﻴﺜﻮﻛﺴﻲ ‪-4))) - 2-‬ﻣﻴﺜﻮﻛﺴﻲ ‪، 3-‬‬ ‫•‬
‫ﺳﻠﻔﻴﻨﻴﻞ( ‪1-‬ﺡ‪-‬ﺑﻨﺰﻳﻤﻴﺪﺍﺯﻭﻝ )ﻟﻮﺳﻴﻚ(‬
‫ﻭﻫﻮﻣﺬﺑﺬﺏ )ﺑﻴﺮﻳﺪﻳﻦ ‪ N pKa 4.06‬؛ ‪.(benzimidazole NH ، pHa 0.79‬‬ ‫•‬
‫ﻗﻠﻴﻞﺍﻟﺬﻭﺑﺎﻥ ﻓﻲ ﺍﻟﻤﺎء‪ .‬ﺇﻧﻪ ﺣﻤﺾ ﻗﺎﺑﻞ ﻟﻠﺘﻐﻴﺮ ‪ ،‬ﻭﺑﺎﻟﺘﺎﻟﻲ ‪ ،‬ﻳﺘﻢ ﺻﻴﺎﻏﺘﻪ‬
‫ﻛﻤﺎﺗﺄﺧﺮ ﺍﻹﻓﺮﺍﺝ‬
‫ﺗﺤﺘﻮﻱﻋﻠﻰ ﻣﻌﻮﻱ‪-‬‬ ‫ﻛﺒﺴﻮﻻﺕ‬
‫ﺣﺒﻴﺒﺎﺕﻣﻐﻠﻔﺔ‪.‬‬
‫ﻳﺘﻢﺍﺳﺘﻘﻼﺑﻪ‪.‬‬ ‫ﺃﻭﻝﺇﺟﺘﻴﺎﺯ‬ ‫•‬
‫ﺃﻭﻣﻴﺒﺮﺍﺯﻭﻝﻋﺒﺎﺭﺓ ﻋﻦ ﺭﻛﻴﺰﺓ ﻟـ ‪CYP3A4‬‬
‫& ‪ → CYP2C19‬ﻣﺜﺒﻂ‬
‫ﻣﺆﻛﺴﺪ)ﻻ ﻳﺜﺒﻂ ﺇﻳﺰﻭﻣﻴﺒﺮﺍﺯﻭﻝ ﺑﺸﻜﻞ ﻛﺒﻴﺮ( ﺍﺳﺘﻘﻼﺏ ﺍﻷﺩﻭﻳﺔ ﺍﻷﺧﺮﻯ ﺗﺮﻛﻴﺰ ﺍﻟﺒﻼﺯﻣﺎ ﻟﻠﺒﻨﺰﻭﺩﻳﺎﺯﻳﺒﻴﻦ‬
‫ﻭﺍﻟﻔﻴﻨﻴﺘﻮﻳﻦﻭﺍﻟﻮﺍﺭﻓﺎﺭﻳﻦ‪.‬‬
‫ﻳﺤﺘﻮﻱﺃﻭﻣﻴﺒﺮﺍﺯﻭﻝ )ﺧﻠﻴﻂ ﺭﺍﺳﻴﻤﻲ( ﻋﻠﻰ ﺗﺒﺎﻳﻦ ﻓﺮﺩﻱ ﺑﻴﻦ ﻣﺠﻤﻮﻋﺎﺕ ﻣﺴﺘﻘﻠﺐ ‪ 2C19‬ﻭﺍﺳﻌﺔ ﺍﻟﻨﻄﺎﻕ‬ ‫•‬
‫ﻭﺑﻄﻴﺉﺔ‪.‬ﺗﺄﺛﻴﺮ ﺍﻟﺴﻜﺎﻥ ﺍﻟﻤﺘﻐﻴﺮ )ﺍﻟﻌﺮﻕ( ﻋﻠﻰ (‪ S - )-( - enantiomer )esomeprazole‬ﺃﻗﻞ ﻣﻦ‬
‫ﺃﻭﻣﻴﺒﺮﺍﺯﻭﻝ‪.‬‬
‫ﺍﻟﻌﻤﻞ‪:‬ﻣﻦ ‪ 24‬ﺇﻟﻰ ‪ 72‬ﺳﺎﻋﺔ‪.‬‬ ‫•‬
‫ﺷﻜﻞﺟﺮﻋﺎﺕ‪ :‬ﺃﻗﺮﺍﺹ ﻣﺘﺄﺧﺮﺓ ﺍﻹﻃﻼﻕ )‪ 20‬ﻣﺠﻢ( ﻭﻛﺒﺴﻮﻻﺕ )‪ 20‬ﻣﺠﻢ ﻭ ‪ 40‬ﻣﺠﻢ(‬ ‫•‬

‫ﺏ( ﻣﻐﻨﻴﺴﻴﻮﻡ ﺇﻳﺰﻭﻣﻴﺒﺮﺍﺯﻭﻝ‬

‫• )ﻧﻴﻜﺴﻴﻮﻡ(‬
‫ﺇﻧﻪ‪ S-enantiomer‬ﻷﻭﻣﻴﺒﺮﺍﺯﻭﻝ‬ ‫•‬
‫ﻟﺪﻳﻪﻧﺸﺎﻁ ‪ PPI‬ﺃﻛﺒﺮ ﻗﻠﻴﻼ ً‪ ،‬ﻭﺇﺯﺍﻟﺔ ﺃﻗﻞ ﺑﺜﻼﺙ ﻣﺮﺍﺕ ﻣﻦ ‪) R-isomer‬ﺑﺴﺒﺐ ﺍﻷﻳﺾ ﺍﻷﺑﻄﺄ ﺑﻨﺴﺒﺔ ‪2C19‬‬ ‫•‬
‫(‪.‬‬
‫ﺃﺷﻜﺎﻝﺍﻟﺠﺮﻋﺎﺕ‪ :‬ﻛﺒﺴﻮﻻﺕ ﻣﺘﺄﺧﺮﺓ ﺍﻹﻃﻼﻕ )‪ 20‬ﺃﻭ ‪ 40‬ﻣﺠﻢ( ﻭﻣﺴﺤﻮﻕ ﻣﻌﻠﻖ )‪ 10‬ﻭ ‪ 20‬ﻭ ‪ 40‬ﻣﺠﻢ(‬ ‫•‬
‫ﻭﻣﺴﺤﻮﻕﻟﻠﺤﻘﻦ )‪ 20‬ﻭ ‪ 40‬ﻣﺠﻢ(‪.‬‬

‫ﺝ( ﻻﻧﺴﻮﺑﺮﺍﺯﻭﻝ‬
‫• )ﺑﺮﻳﻔﺎﺳﻴﺪ(‬
‫ﺃﻋﻠﻰﺍﻟﺘﻮﺍﻓﺮ ﺍﻟﺒﻴﻮﻟﻮﺟﻲ ﺑﻴﻦ ﻣﺜﺒﻄﺎﺕ ﻣﻀﺨﺔ ﺍﻟﺒﺮﻭﺗﻮﻥ‪ .‬ﺍﺭﺗﺒﺎﻁ ﺑﺮﻭﺗﻴﻦ ﺍﻟﺒﻼﺯﻣﺎ‪.٪97 :‬‬ ‫•‬
‫ﻳﺘﻢﺍﺳﺘﻘﻼﺑﻪ ﻓﻲ ﺍﻟﻜﺒﺪ )ﻣﺴﺘﻘﻠﺒﺎﺕ ﺍﻟﺴﻠﻔﻮﻥ ﻭﺍﻟﻬﻴﺪﺭﻭﻛﺴﻲ( ﻭﻳﻄﺮﺡ ﻓﻲ ﺍﻟﺼﻔﺮﺍء ﻭﺍﻟﺒﻮﻝ‪.‬‬ ‫•‬
‫ﺷﻜﻞﺟﺮﻋﺎﺕ‪ :‬ﺃﻗﺮﺍﺹ ﻣﺘﺄﺧﺮﺓ ﺍﻹﻃﻼﻕ ﻭﻣﺘﺤﻠﻠﺔ ﻋﻦ ﻃﺮﻳﻖ ﺍﻟﻔﻢ )‪ 15‬ﻭ ‪ 30‬ﻣﺠﻢ( ‪ ،‬ﻛﺒﺴﻮﻻﺕ ﺗﺄﺧﺮ‬ ‫•‬
‫ﺍﻹﻓﺮﺍﺝ)‪ 5‬ﻭ ‪ 30‬ﻣﺠﻢ( ‪ ،‬ﺣﺒﻴﺒﺎﺕ ﻣﺘﺄﺧﺮﺓ ﺍﻹﻃﻼﻕ ﻟﻠﺘﻌﻠﻴﻖ ﺍﻟﻔﻤﻮﻱ )‪ 15‬ﻭ ‪ 30‬ﻣﺠﻢ( ﻭﻣﺴﺤﻮﻕ ﻟﻠﺤﻘﻦ )‬
‫‪30‬ﻣﺠﻢ ‪ /‬ﻗﺎﺭﻭﺭﺓ( (‬

‫ﺩ( ﺑﺎﻧﺘﻮﺑﺮﺍﺯﻭﻝ ﺍﻟﺼﻮﺩﻳﻮﻡ‬

‫ﻗﺎﺑﻞﻟﻠﺬﻭﺑﺎﻥ ﻓﻲ ﺍﻟﻤﺎء ﺑﺤﺮﻳﺔ‬
‫•‬
‫ﻳﺰﺩﺍﺩﺗﺪﻫﻮﺭﻫﺎ ﻣﻊ ﺯﻳﺎﺩﺓ ﺍﻟﺮﻗﻢ ﺍﻟﻬﻴﺪﺭﻭﺟﻴﻨﻲ‪.‬‬ ‫•‬
‫ﻳﻤﺘﺺﺑﺸﻜﻞ ﺟﻴﺪ ﻭﺳﺮﻳﻊ )‪ ٪77‬ﻣﺘﻮﻓﺮ ﺣﻴﻮﻳﺎ(ً ‪ ،‬ﻭ ‪ ٪98‬ﻳﺮﺗﺒﻂ ﺑﺒﺮﻭﺗﻴﻨﺎﺕ ﺍﻟﺒﻼﺯﻣﺎ‪.‬‬ ‫•‬

‫‪23‬‬
 ‫ﺍﻟﺠﻬﺎﺯﺍﻟﻬﻀﻤﻲ‪ :‬ﻋﻼﺝ ﺍﻟﻘﺮﺣﺔ ﺍﻟﻬﻀﻤﻴﺔ‬ ‫ﺍﻟﻜﻴﻤﻴﺎءﺍﻟﻄﺒﻴﺔ ‪III‬‬

‫ﺍﻹﺧﺮﺍﺝ‪:‬ﺍﻟﺒﻮﻝ ﺑﺸﻜﻞ ﺭﺉﻴﺴﻲ ‪ ،‬ﻭﻳﺨﺮﺝ ﺃﻳﻀﺎً ﻓﻲ ﺍﻟﺒﺮﺍﺯ‪.‬‬ ‫•‬

‫ﺃﺷﻜﺎﻝﺍﻟﺠﺮﻋﺎﺕ‪ :‬ﺃﻗﺮﺍﺹ ﻣﺘﺄﺧﺮﺓ ﺍﻹﻃﻼﻕ )‪ 20‬ﻭ ‪ 40‬ﻣﺠﻢ( ‪ ،‬ﻣﻌﻠﻖ ﻋﻦ ﻃﺮﻳﻖ ﺍﻟﻔﻢ ﻣﺘﺄﺧﺮ ﺍﻟﺘﺤﺮﺭ )‪40‬‬ ‫•‬
‫ﻣﺠﻢ( ﻭﻣﺴﺤﻮﻕ ﻟﻠﺤﻘﻦ )‪ 40‬ﻣﺠﻢ(‬

‫ﻩ( ﺭﺍﺑﻴﺒﺮﺍﺯﻭﻝ ﺍﻟﺼﻮﺩﻳﻮﻡ‬

‫• )ﺃﺳﻴﻔﻴﻜﺲ(‬
‫ﻗﺎﻋﺪﺗﻬﺎﺍﻟﻀﻌﻴﻔﺔ ﻭﻫﻲ ﺣﻤﻮﺿﺔ )ﻣﺬﺑﺬﺏ( ﺗﺴﻬﻞ ﺗﺮﻛﻴﺒﻬﺎ ﻛﻤﻠﺢ ﺻﻮﺩﻳﻮﻡ‪.‬‬ ‫•‬
‫ﺷﻜﻞﺟﺮﻋﺎﺕ‪ :‬ﺃﻗﺮﺍﺹ ﻣﺘﺄﺧﺮﺓ ﺍﻹﻃﻼﻕ )‪ 20‬ﻣﺠﻢ(‬ ‫•‬

‫‪.3‬ﻭﻛﻼء ﻣﻀﺎﺩﺍﺕ ﺍﻟﻤﺴﻜﺎﺭﻳﻦ‬

‫ﺃﻧﻬﺎﺗﻘﻠﻞ ﻣﻦ ﺇﻓﺮﺍﺯ ﺍﻟﺤﻤﺾ ﻭﺍﻟﺒﻴﺒﺴﻴﻦ ﻧﺘﻴﺠﺔ ﻟﺘﻘﻠﻴﻞ ﺍﻟﻨﻐﻤﺔ ﺍﻟﻜﻮﻟﻴﻨﻴﺔ ﻋﻦ‬ ‫•‬
‫ﻃﺮﻳﻖﻣﻨﻊ ﺍﻟﻤﺴﻜﺎﺭﻳﻦ ‪ -3M‬ﺍﻟﻤﺴﺘﻘﺒﻼﺕ ﻓﻲ ﺍﻟﺨﻼﻳﺎ ﺍﻟﺠﺪﺍﺭﻳﺔ ﻟﻠﻤﻌﺪﺓ ﻭ ‪-1.M‬‬
‫ﻣﺴﺘﻘﺒﻼﺕﺍﻟﺨﻼﻳﺎ ﺍﻟﺘﻲ ﺗﻮﻓﺮ ﺍﻟﺘﺤﻔﻴﺰ ﺍﻟﻜﻮﻟﻴﻨﻲ ﻹﻓﺮﺍﺯ ﺍﻟﺤﻤﺾ ‪ ،‬ﻣﺜﻞ ﺧﻼﻳﺎ‬
‫ﺍﻟﺠﺎﺳﺘﺮﻳﻦ‪.‬‬
‫ﺃﻧﻬﺎﺗﻄﻴﻞ ﻭﻗﺖ ﺇﻓﺮﺍﻍ ﺍﻟﻤﻌﺪﺓ‪.‬‬ ‫•‬
‫ﺑﺎﻹﺿﺎﻓﺔﺇﻟﻰ ﺫﻟﻚ ‪ ،‬ﻓﺈﻥ ﺍﻟﺘﺄﺛﻴﺮﺍﺕ ﺍﻟﻤﻀﺎﺩﺓ ﻟﻠﺘﺸﻨﺞ ﻫﻲ ﺇﺣﺪﻯ ﻣﻴﺰﺍﺗﻪ‬ ‫•‬
‫ﺍﻟﻤﺨﺘﻠﻔﺔﻋﻦ ﺍﻷﺩﻭﻳﺔ ﺍﻷﺧﺮﻯ ‪ ،‬ﻭﺑﺴﺒﺐ ﻫﺬﻩ ﺍﻟﺘﺄﺛﻴﺮﺍﺕ ‪ ،‬ﻓﺈﻧﻬﺎ ﺗﻮﻓﺮ ﺗﺴﻜﻴﻦ‬
‫ﺍﻵﻻﻡ‪.‬‬

‫ﺃ( ‪Pirenzepine‬‬
‫• ﻭﻫﻮﻋﺎﻣﻞ ﻣﻀﺎﺩ ﻟﻠﻤﺴﻜﺎﺭﻳﻦ ﻳﺴﺘﺨﺪﻡ ﻟﻌﻼﺝ ﺍﻟﻘﺮﺣﺔ ﺍﻟﻬﻀﻤﻴﺔ ﻭﻗﺮﺣﺔ ﺍﻟﻤﻌﺪﺓ ﻭﻗﺮﺣﺔ ﺍﻻﺛﻨﻲ ﻋﺸﺮ‪.‬‬
‫ﺇﻧﻪﺩﻭﺍء ﻣﻀﺎﺩ ﻟﻠﺘﺄﺛﻴﺮﺍﺕ ﺍﻻﻧﺘﻘﺎﺉﻴﺔ ﻳﻌﻤﻞ ﺑﺸﻜﻞ ﺍﻧﺘﻘﺎﺉﻲ‪.‬‬ ‫•‬
‫ﺇﻧﻪﻳﻤﺎﺭﺱ ﺗﺄﺛﻴﺮﺍً ﺍﻧﺘﻘﺎﺉﻴﺎً ﻋﻦ ﻃﺮﻳﻖ ﺍﻟﺤﺠﺐ ﺍﻻﻧﺘﻘﺎﺉﻲ‬ ‫•‬
‫ﻓﻘﻂﻟـ ‪1.M‬ﻧﻮﻉ ﻓﺮﻋﻲ ﻣﻦ ﺍﻟﻤﺴﺘﻘﺒﻼﺕ ﺍﻟﻤﺴﻜﺎﺭﻳﻨﻴﺔ‪.‬‬

‫ﻋﻠﻰﺍﻟﺮﻏﻢ ﻣﻦ ﺃﻧﻪ ﻳﺤﺘﻮﻱ ﻋﻠﻰ ﺑﻨﻴﺔ ﺛﻼﺛﻴﺔ ﺍﻟﺤﻠﻘﺎﺕ ‪ ،‬ﺇﻻ ﺃﻧﻪ‬ ‫•‬
‫ﻟﻴﺲﻟﻪ ﻃﺎﺑﻊ ﻣﺤﺐ ﻟﻠﺪﻫﻮﻥ‪.‬‬

‫ﻣﺪﺓﻋﻤﻠﻬﺎ ﻃﻮﻳﻠﺔ‪.‬‬ ‫•‬

‫ﺏ‪.‬ﻣﻀﺎﺩﺍﺕﺍﻟﺤﻤﻮﺿﺔ )ﺍﻟﻤﺤﺎﻳﺪﺓ ﺍﻟﺤﻤﻀﻴﺔ(‬

‫ﺁﻟﻴﺔﺍﻟﻌﻤﻞ )‪ :(MOA‬ﻣﻀﺎﺩﺍﺕ ﺍﻟﺤﻤﻮﺿﺔ ﻫﻲ ﻗﻮﺍﻋﺪ ﺿﻌﻴﻔﺔ ﺗﺘﻔﺎﻋﻞ ﻣﻊ ﺣﻤﺾ ﺍﻟﻬﻴﺪﺭﻭﻛﻠﻮﺭﻳﻚ ﺍﻟﻤﻌﺪﻱ‬ ‫•‬
‫ﻟﺘﻜﻮﻳﻦﺍﻟﻤﻠﺢ ﻭﺍﻟﻤﺎء → ↓ ﺍﻟﺤﻤﻮﺿﺔ ‪ ،‬ﻭﻗﺪ ﺗﻌﺰﺯ ﺃﻳﻀﺎً ﺁﻟﻴﺎﺕ ﺍﻟﺪﻓﺎﻉ ﺍﻟﻤﺨﺎﻃﻲ )ﻣﻦ ﺧﻼﻝ ↑ ﻣﻦ‬
‫ﺍﻟﺒﺮﻭﺳﺘﺎﺟﻼﻧﺪﻳﻦ(‪.‬‬
‫ﻧﺎﻫﻜﻮ‪+3‬ﺣﻤﺾ ﺍﻟﻬﻴﺪﺭﻭﻛﻠﻮﺭﻳﻚ → ‪ +2NaCl + CO‬ﺡ‪2‬ﺱ‪ .‬ﻛﺮﺑﻮﻧﺎﺕ‬ ‫ﺍ‬
‫ﺍﻟﻜﺎﻟﺴﻴﻮﻡ‪ +22HCl → CaCl+3‬ﺷﺮﻛﺔ‪ +2‬ﺡ‪2‬ﺱ‪ .‬ﻣﻠﻎ )ﻳﺎ(‪Mg )Cl(+2‬‬ ‫ﺍ‬
‫→ ‪ 2 +22HCl‬ﺡ‪2‬ﺱ‪ .‬ﺁﻝ )ﺃﻭﻩ(‪ 3 +33HCl → Al )Cl(+3‬ﺡ‪2‬ﺱ‪.‬‬ ‫ﺍ‬
‫ﺍﻟﺼﻠﺢ‪:‬ﻣﺠﻤﻊ ﺃﻟﻮﻣﻴﻨﺎﺕ ﻫﻴﺪﺭﻭﻛﺴﻲ ﻣﻐﻨﻴﺴﻴﻮﻡ‪.‬‬ ‫ﺍ‬
‫ﺍ‬
‫ﺳﻴﻤﻴﺜﻴﻜﻮﻥ‪:‬ﻭﻫﻮ ﻣﺎﺩﺓ ﺧﺎﻓﻀﺔ ﻟﻠﺘﻮﺗﺮ ﺍﻟﺴﻄﺤﻲ ﻗﺪ ﺗﻘﻠﻞ ﻣﻦ ﺍﻟﺮﻏﻮﺓ ﻭﺑﺎﻟﺘﺎﻟﻲ ﺍﺭﺗﺠﺎﻉ‬ ‫ﺍ‬
‫ﺍﻟﻤﺮﻱء‪.‬‬

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 ‫ﺍﻟﺠﻬﺎﺯﺍﻟﻬﻀﻤﻲ‪ :‬ﻋﻼﺝ ﺍﻟﻘﺮﺣﺔ ﺍﻟﻬﻀﻤﻴﺔ‬ ‫ﺍﻟﻜﻴﻤﻴﺎءﺍﻟﻄﺒﻴﺔ ‪III‬‬

‫ﻋﺪﻡﺍﻛﺘﻤﺎﻝ ﺍﻣﺘﺼﺎﺹ ﺍﻟﺠﻬﺎﺯ ﺍﻟﻬﻀﻤﻲ )‪+3Al‬ﻣﻠﻎ‪ & ،+2‬ﻛﺎﻟﻴﻔﻮﺭﻧﻴﺎ‪ ، (+2‬ﻭﺗﻄﻬﻴﺮﻫﺎ ﻣﻦ ﺍﻟﻤﻌﺪﺓ ﺍﻟﻔﺎﺭﻏﺔ ﻓﻲ ‪30‬‬ ‫•‬
‫ﺩﻗﻴﻘﺔ‪.‬ﺗﻄﻴﻞ ﺍﻷﻃﻌﻤﺔ ﺍﻟﻤﻔﻌﻮﻝ ﺇﻟﻰ ﺣﻮﺍﻟﻲ ‪ 3-2‬ﺳﺎﻋﺎﺕ‪.‬‬
‫ﺍﻵﺛﺎﺭﺍﻟﺴﻠﺒﻴﺔ‪:‬‬ ‫•‬
‫ﻳﻤﻜﻦﺃﻥ ﺗﺴﺒﺐ ﻣﻀﺎﺩﺍﺕ ﺍﻟﺤﻤﻮﺿﺔ ﺍﻟﻤﺤﺘﻮﻳﺔ ﻋﻠﻰ ﺍﻟﻜﺮﺑﻮﻧﺎﺕ ﺍﻟﺘﺠﺸﺆ ﻭﺍﻟﻐﺜﻴﺎﻥ ﻭﺍﻧﺘﻔﺎﺥ ﺍﻟﺒﻄﻦ ﻭﺍﻧﺘﻔﺎﺥ‬ ‫ﺍ‬
‫ﺍﻟﺒﻄﻦ)ﺑﺴﺒﺐ ﺛﺎﻧﻲ ﺃﻛﺴﻴﺪ ﺍﻟﻜﺮﺑﻮﻥ‪2‬ﺇﻧﺘﺎﺝ(‪.‬‬
‫ﺍﻣﺘﺼﺎﺹﻛﻠﻮﺭﻳﺪ ﺍﻟﺼﻮﺩﻳﻮﻡ ← ﻳﺆﺩﻱ ﺇﻟﻰ ﺗﻔﺎﻗﻢ ﺍﺣﺘﺒﺎﺱ ﺍﻟﺴﻮﺍﺉﻞ ﻓﻲ ﺍﺿﻄﺮﺍﺑﺎﺕ ﺍﻟﻘﻠﺐ ﻭﺍﻷﻭﻋﻴﺔ‬ ‫ﺍ‬
‫ﺍﻟﺪﻣﻮﻳﺔ‪.‬ﻧﺎﻫﻜﻮ‪3& CaCO3‬ﻗﺪ ﻳﺴﺒﺐ ﻗﻼء ﺍﺳﺘﻘﻼﺑﻲ‪ .‬ﻗﺪ ﻳﺤﻔﺰ ﺍﻟﻜﺎﻟﺴﻴﻮﻡ ﺃﻳﻀﺎً ﻋﻠﻰ ﺇﻓﺮﺍﺯ ﺣﻤﺾ‬ ‫ﺍ‬
‫ﺍﻻﺭﺗﺪﺍﺩ‪.‬‬
‫ﻣﻠﻎ‪+‬ﻗﺪ ﻳﺴﺒﺐ ﺍﻹﺳﻬﺎﻝ ﺍﻷﺳﻤﻮﺯﻱ ‪ ،‬ﺑﻴﻨﻤﺎ ‪+Al‬ﻳﺴﺒﺐ ﺍﻹﻣﺴﺎﻙ‪ .‬ﻳﺘﻢ ﺍﻟﺠﻤﻊ ﺑﻴﻦ ﻫﺬﻩ ﺍﻟﻌﻮﺍﻣﻞ‬ ‫ﺍ‬
‫)‪ (magaldrate‬ﻟﻤﻨﻊ ﺗﻠﻚ ﺍﻹﺟﺮﺍءﺍﺕ‪.‬‬
‫ﺗﻔﺎﻋﻼﺕﺍﻟﻐﺬﺍء ﻭﺍﻟﺪﻭﺍء‪ :‬ﺍ‬ ‫•‬
‫ﺍﻟﻤﻔﺮﻁ‪ +3& CaCO3NaHCO‬ﻛﺎﻟﻴﻔﻮﺭﻧﻴﺎ‪ -+2‬ﺗﺤﺘﻮﻱ ﻋﻠﻰ ﻣﺸﺘﻘﺎﺕ ﺍﻟﺤﻠﻴﺐ ‪ -‬ﻣﺘﻼﺯﻣﺔ ﺍﻟﺤﻠﻴﺐ‬
‫ﺍﻟﻘﻠﻮﻱ)ﻓﺮﻁ ﻛﺎﻟﺴﻴﻮﻡ ﺍﻟﺪﻡ ‪ ،‬ﻗﺼﻮﺭ ﻛﻠﻮﻱ ‪ ،‬ﻗﻼء ﺍﺳﺘﻘﻼﺑﻲ(‪.‬‬
‫ﺗﻘﻠﻞﻣﻀﺎﺩﺍﺕ ﺍﻟﺤﻤﻮﺿﺔ ﻣﻦ ﺍﻣﺘﺼﺎﺹ ﺍﻟﺘﺘﺮﺍﺳﻴﻜﻠﻴﻦ ﻭﺍﻟﻔﻠﻮﺭﻭﻛﻴﻨﻮﻟﻮﻧﺎﺕ ﻭﺍﻹﻳﺘﺮﺍﻛﻮﻧﺎﺯﻭﻝ ﻭﺍﻟﺤﺪﻳﺪ‪.‬‬ ‫ﺍ‬
‫ﻭﺑﺎﻟﺘﺎﻟﻲ ‪،‬ﻻ ﻳﻨﺒﻐﻲ ﺇﻋﻄﺎء ﻣﻀﺎﺩﺍﺕ ﺍﻟﺤﻤﻮﺿﺔ ﻓﻲ ﻏﻀﻮﻥ ﺳﺎﻋﺘﻴﻦ ﻣﻦ ﺟﺮﻋﺎﺕ ﺍﻷﺩﻭﻳﺔ ﺍﻷﺧﺮﻯ‪.‬‬

‫(‪C. PROSTAGLANDINS )PG‬‬

‫ﺍﻟﺒﺮﻭﺳﺘﺎﺟﻼﻧﺪﻳﻦﻋﺒﺎﺭﺓ ﻋﻦ ﺃﺣﻤﺎﺽ ﺩﻫﻨﻴﺔ ﻏﻴﺮ ﻣﺸﺒﻌﺔ ﺫﺍﺕ ‪ 20‬ﻛﺮﺑﻮﻧﺎً ﻣﺸﺘﻘﺔ ﻣﻦ ﺣﻤﺾ ﺍﻷﺭﺍﻛﻴﺪﻭﻧﻴﻚ‪.‬‬ ‫•‬

‫ﺃ( ﻣﻴﺴﻮﺑﺮﻭﺳﺘﻮﻝ‬
‫ﻭﻫﻮﻣﺸﺘﻖ ﺷﺒﻪ ﺻﻨﺎﻋﻲ ﻣﻦ ‪.PGE1‬‬ ‫•‬
‫ﺇﻧﻪﻣﺴﺘﻘﺮ ﺣﻴﻮﻳﺎً ﺑﺴﺒﺐ ﺑﺪﺍﺉﻞ ‪ 16‬ﻣﻴﺜﻴﻞ ﻭ ‪16‬‬ ‫•‬
‫ﻫﻴﺪﺭﻭﻛﺴﻲ‪.‬‬
‫ﻳﺘﻮﻓﺮﺧﻠﻴﻂ ﻣﻦ ﺩﻳﺎﺳﺘﻴﺮﻭﻣﺮﺍﺕ ﺍﻟﻤﻴﺰﻭﺑﺮﻭﺳﺘﻮﻝ ‪ ،‬ﻭﻟﻜﻦ‬ ‫•‬
‫ﻣﻌﻈﻢﺍﻟﻨﺸﺎﻁ ﻳﺄﺗﻲ ﻣﻦ ‪.11R ، 16Sisomers‬‬

‫ﻟﻪﺗﺄﺛﻴﺮﺍﺕ ﻣﻀﺎﺩﺓ ﻟﻺﻓﺮﺍﺯ ﻭﻣﻀﺎﺩﺓ ﻟﻠﺨﻼﻳﺎ ﻣﻤﺎﺛﻠﺔ ﻟـ ‪.PGE1‬‬ ‫•‬

‫ﻳﻌُﺘﻘﺪﺃﻥ ﺍﻟﺤﻤﺎﻳﺔ ﺍﻟﺨﻠﻮﻳﺔ ﻧﺎﺗﺠﺔ ﻋﻦ ﺇﻓﺮﺍﺯ ﺍﻟﻤﺨﺎﻁ ﻭﺍﻟﺒﻴﻜﺮﺑﻮﻧﺎﺕ ‪ ↑ ،‬ﺗﺪﻓﻖ ﺍﻟﺪﻡ ﻓﻲ ﺍﻟﻐﺸﺎء ﺍﻟﻤﺨﺎﻃﻲ‪.‬‬ ‫•‬

‫ﻭﻫﻮﺩﻭﺍء ﺃﻭﻟﻲ ﻳﺘﺤﻠﻞ ﺑﺎﻟﻤﺎء ﺑﻮﺍﺳﻄﺔ ﺇﻧﺰﻳﻤﺎﺕ ﺍﻹﺳﺘﺮﻳﺰ ﺇﻟﻰ ﺣﻤﺾ ﺍﻟﻜﺮﺑﻮﻛﺴﻴﻞ ﺍﻟﻨﺸﻂ‪.‬‬ ‫•‬

‫ﺩ‪-‬ﻋﻮﺍﻣﻞ ﺣﻤﺎﻳﺔ ﺍﻟﻐﺸﺎء ﺍﻟﻤﺨﺎﻃﻲ‬

‫ﺃ( ﺳﻮﻛﺮﺍﻟﻔﺎﺕ‬
‫• ﺇﻧﻪﻣﺮﻛﺐ ﻫﻴﺪﺭﻭﻛﺴﻴﺪ ﺍﻷﻟﻮﻣﻨﻴﻮﻡ ﻹﺳﺘﺮ ﺃﻭﻛﺘﺎﺳﻠﻔﺎﺕ‬
‫ﻣﻦﺍﻟﺴﻜﺮﻭﺯ‪ .‬ﺇﻧﻪ ﻏﻴﺮ ﻗﺎﺑﻞ ﻟﻠﺬﻭﺑﺎﻥ ﻋﻤﻠﻴﺎ ﻓﻲ ﺍﻟﻤﺎء ﻭﻗﺎﺑﻞ ﻟﻠﺬﻭﺑﺎﻥ ﻓﻲ‬
‫ﺍﻷﺣﻤﺎﺽﻭﺍﻟﻘﻮﺍﻋﺪ ﺍﻟﻘﻮﻳﺔ‪.‬‬

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 ‫ﺍﻟﺠﻬﺎﺯﺍﻟﻬﻀﻤﻲ‪ :‬ﻋﻼﺝ ﺍﻟﻘﺮﺣﺔ ﺍﻟﻬﻀﻤﻴﺔ‬ ‫ﺍﻟﻜﻴﻤﻴﺎءﺍﻟﻄﺒﻴﺔ ‪III‬‬

‫ﻳﻤﺎﺭﺱﺗﺄﺛﻴﺮﻩ ﺍﻟﻤﻀﺎﺩ ﻟﻠﻘﺮﺣﺔ ﻣﻦ ﺧﻼﻝ ﺍﻟﺘﺄﺛﻴﺮ ﺍﻟﻤﻮﺿﻌﻲ ﻭﻟﻴﺲ ﺍﻟﻨﻈﺎﻣﻲ‪.‬‬ ‫•‬

‫ﻟﺪﻳﻪﻗﺪﺭﺓ ﺿﺉﻴﻠﺔ ﻋﻠﻰ ﺗﺤﻴﻴﺪ ﺍﻷﺣﻤﺎﺽ ﺃﻭ ﺍﻟﺘﺨﺰﻳﻦ ﺍﻟﻤﺆﻗﺖ ﻓﻲ ﺍﻟﺠﺮﻋﺎﺕ ﺍﻟﻌﻼﺟﻴﺔ‪.‬‬ ‫•‬
‫‪.‬ﻳﺮﺗﺒﻂﺳﻮﻛﺮﺍﻟﻔﺎﺕ ﺑﺸﻜﻞ ﺗﻔﻀﻴﻠﻲ ﺑﻤﻮﻗﻊ ﺍﻟﻘﺮﺣﺔ ﻟﺘﺸﻜﻴﻞ ﺣﺎﺟﺰ ﻭﻗﺎﺉﻲ ﻳﻤﻨﻊ ﺗﻌﺮﺽ ﺍﻵﻓﺔ ﻟﻠﺤﻤﺾ‬ ‫•‬
‫ﻭﺍﻟﺒﻴﺒﺴﻴﻦ‪.‬ﺑﺎﻹﺿﺎﻓﺔ ﺇﻟﻰ ﺫﻟﻚ ‪ ،‬ﻳﻤﺘﺺ ﺍﻟﺒﻴﺒﺴﻴﻦ ﻭﺃﻣﻼﺡ ﺍﻟﺼﻔﺮﺍء ‪MOA:‬‬
‫ﻗﺪﻳﺆﺩﻱ ﺗﻨﺎﻭﻝ ﺳﻮﻛﺮﺍﻟﻔﺎﺕ ﻓﻲ ﻭﻗﺖ ﻭﺍﺣﺪ ﺇﻟﻰ ﺗﻘﻠﻴﻞ ﺍﻟﺘﻮﺍﻓﺮ ﺍﻟﺒﻴﻮﻟﻮﺟﻲ ﻟﺒﻌﺾ ﺍﻟﻌﻮﺍﻣﻞ )ﻣﺜﻞ‬ ‫•‬
‫ﺍﻟﺘﺘﺮﺍﺳﻴﻜﻠﻴﻦﺃﻭ ﺍﻟﻔﻴﻨﻴﺘﻮﻳﻦ ﺃﻭ ﺍﻟﺪﻳﺠﻮﻛﺴﻴﻦ ﺃﻭ ﺍﻟﺴﻴﻤﻴﺘﻴﺪﻳﻦ(‪.‬‬

‫ﺩﻛﺘﻮﺭﺳﺎﻡ ﺩﻭﺑﺎ ﻓﺎﺭﻡ‪ .‬ﺗﺸﻴﻢ‪ .‬ﺩﻛﺘﻮﺭﺍﻩ‪.‬‬

‫ﻣﺮﺍﺟﻊ‪:‬‬
‫‪1. Wilson & Gisvold's، Textbook of Organic Medical Medical and Pharmaceutical Chemistry، 12th edn.‬‬
‫‪.2‬ﻣﺒﺎﺩﺉ ﻓﻮﻱ ﻟﻠﻜﻴﻤﻴﺎء ﺍﻟﻄﺒﻴﺔ ‪ ،‬ﺍﻟﻄﺒﻌﺔ ﺍﻟﺴﺎﺑﻌﺔ‪.‬‬
‫‪.3‬ﺃﻛﻐﻮﻥ ﻭﺁﺧﺮﻭﻥ‪ .‬ﻓﺎﺭﻣﺎﺳﻮﺗﻴﻚ ﻛﻴﻤﻴﺎ ؛‬
‫؛‪4. Drugbank.com‬‬
‫‪https://pubchem.ncbi.nlm.nih.gov5. Pubchem‬‬
‫؛‪6. Katzung، Basic & Clinical Pharmacology، 10th edn‬‬
‫‪.7‬ﺍﻟﻤﺮﺍﺟﻌﺎﺕ ﺍﻟﻤﺼﻮﺭﺓ ﻟﻴﺒﻴﻨﻜﻮﺕ ‪ ،‬ﻋﻠﻢ ﺍﻷﺩﻭﻳﺔ ‪ ،‬ﺍﻟﻄﺒﻌﺔ ﺍﻟﺮﺍﺑﻌﺔ ؛‬
‫؛‪8. Goodman & Gilman's، The Pharmacological Basis of Therapeutics، 11th edn.‬‬
‫ﺍﻟﺒﺮﻣﺠﻴﺎﺕ‪ChemDraw 12 .1:‬؛‬

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