‫ﻣﻴﺘﻔﻮرﻣﻴﻦ‬

‫ﻣﺮﻛﺐ ﻛﻴﻤﻴﺎﺋﻲ‬

‫( )اﺳﻢ ﻣﻌﺘﻤﺪ‬ ‫ﻳُ ﻌﺪ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ اﻟﺬي ﻳُ ﺒﺎع ﺗﺤﺖ اﻻﺳﻢ اﻟﺘﺠﺎري ﺟﻠﻮﻛﻮﻓﺎج )ﺑﺎﻹﻧﺠﻠﻴﺰﻳﺔ‪Glucophage :‬‬
‫اﻟﻤﻠﻜﻴﺔ‪ُ ،‬ﻳ ّ‬
‫ﺴﻮق ﺑﺎﻷﺳﻤﺎء ﺟﻠﻮﻛﻮﻓﺎج‪ ،‬وﺟﻠﻮﻛﻮﻣﻴﻦ‪ ،‬وﻣﻴﺘﻔﻮرال‪،‬‬ ‫ّ‬ ‫ﻣﺴﺠﻞ‬
‫ّ‬ ‫ﺑﺮﻳﻄﺎﻧﻲ‪ ،‬اﺳﻢ ﻣﻌﺘﻤﺪ أﻣﺮﻳﻜﻲ‪ ،‬اﺳﻢ دوﻟﻲ ﻏﻴﺮ‬
‫وﺳﻴﻮﻓﻮر‪ ،‬ودﻳﺎﻟﻮن‪ ،‬وﺑﺮوت‪ ،‬وﻛﺎرﺑﻮﻓﺎج‪ ،‬ورﻳﻮﻣﻴﺖ‪ ،‬وﻓﻮرﻣﻴﺖ‪ ،‬وﻓﻮرﺗﺎﻣﻴﺖ‪ ،‬وﻏﻠﻮﻣﺘﺰا‪ ،‬وأوﺑﻴﻤﺖ‪ ،‬وﻏﻠﻮﻓﻮرﻣﻴﻦ‪ ،‬ودﻳﺎﻧﺒﻴﻦ‪،‬‬
‫ودﻳﺎﺑﻴﻜﺲ‪ ،‬ودﻳﺎﻓﻮرﻣﻴﻦ‪ ،‬وﻣﻴﺘﻔﻮﻏﺎﻣﺎ(‪ ،‬دواء ﺧﺎﻓﺾ ﻟﺴﻜﺮ اﻟﺪم ﻳﺆﺧﺬ ﻋﻦ ﻃﺮﻳﻖ اﻟﻔﻢ ﻣﻦ ﻓﺌﺔ اﻟﺒﻴﻐﻮاﻧﻴﺪ‪ .‬وﻫﻮ ﺧﻂ اﻟﻌﻼج‬
‫اﻷول ﻟﻌﻼج اﻟﺴﻜﺮي اﻟﻨﻤﻂ اﻟﺜﺎﻧﻲ‪ [2][1]،‬ﺧﺎﺻﺔ ﻓﻲ اﻷﺷﺨﺎص اﻟﺬﻳﻦ ﻳﻌﺎﻧﻮن ﻣﻦ زﻳﺎدة اﻟﻮزن أو اﻟﺴﻤﻨﺔ‪ [3].‬ﻛﻤﺎ أﻧﻬﺎ ﺗﺴﺘﺨﺪم ﻓﻲ‬
‫ﻋﻼج ﻣﺘﻼزﻣﺔ ﺗﻜﻴﺲ اﻟﻤﺒﺎﻳﺾ‪ [1].‬ﻻ ﻳﺮﺗﺒﻂ ﺑﺰﻳﺎدة اﻟﻮزن‪ [4]،‬وﻳﺘﻢ ﺗﻨﺎوﻟﻪ ﻋﻦ ﻃﺮﻳﻖ اﻟﻔﻢ‪ [1].‬ﻳﺴﺘﺨﺪم أﺣﻴﺎ ًﻧﺎ ﻛﺈﺿﺎﻓﺔ ﺧﺎرج‬
‫ﻓﻴﻨﻴﻠﺰﻳﻦ‪[8][7][6][5].‬‬ ‫اﻟﻤﻠﺼﻖ ﻟﺘﻘﻠﻴﻞ ﻣﺨﺎﻃﺮ زﻳﺎدة اﻟﻮزن ﻟﺪى اﻷﺷﺨﺎص اﻟﺬﻳﻦ ﻳﺘﻨﺎوﻟﻮن ﻣﻀﺎدات اﻟﺬﻫﺎن وﻛﺬﻟﻚ‬
 ‫ﻣﻴﺘﻔﻮرﻣﻴﻦ‬

‫أﺳﻤﺎء أﺧﺮى‬

N,N-Dimethylimidodicarbonimidic diamide

‫اﻟﻤﻌﺮﻓﺎت‬

http://www.commonchemistry.org/ChemicalDetail.aspx?ref=) 657-24-9 CAS ‫رﻗﻢ‬

  (657-24-9
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=) 4091 (PubChem) ‫ﺑﻮب ﻛﻴﻢ‬
  (4091
‫ﻣﻮاﺻﻔﺎت اﻹدﺧﺎل اﻟﻨﺼﻲ اﻟﻤﺒﺴﻂ ﻟﻠﺠﺰﻳﺌﺎت‬
[C[n](C):c(:[nH]):[nH]:c(:[nH]):[nH2

CN(C)C(=N)NC(N)=N

‫اﻟﻤﻌﺮف اﻟﻜﻴﻤﻴﺎﺋﻲ اﻟﺪوﻟﻲ‬

1S/C4H11N5/c1-9(2)4(7)8-3(5)6/h1-2H3,(H5,5,6,7,8) 
Key: XZWYZXLIPXDOLR-UHFFFAOYSA-N 

‫اﻟﺨﻮاص‬

C4H11N5 ‫ﺻﻴﻐﺔ ﻛﻴﻤﻴﺎﺋﻴﺔ‬

1−‫ﻣﻮل‬.‫غ‬ 129.16 ‫ﻛﺘﻠﺔ ﻣﻮﻟﻴﺔ‬

1.254 log P

‫ﻋﻠﻢ اﻷدوﻳﺔ‬

60%–50 ‫ﺗﻮاﻓﺮ ﺣﻴﻮي‬

 ‫‪Oral‬‬ ‫ﻃﺮﻳﻖ اﻟﺘﻨﺎول‬
‫‪hours 6.2‬‬ ‫‪Elimination‬‬
‫‪half-life‬‬

‫‪Renal‬‬ ‫إﺧﺮاج‬

‫‪(POM(UK) ℞-only(US‬‬ ‫اﻟﻮﺿﻊ اﻟﻘﺎﻧﻮﻧﻲ‬

‫ﻣﺮﻛﺒﺎت ﻣﺘﻌﻠﻘﺔ‬

‫‪Dimethylurea‬‬ ‫ﻣﺮﻛﺒﺎت ذات ﻋﻼﻗﺔ‬

‫‪Noxytiolin‬‬

‫‪Tetramethylguanidine-1,1,3,3‬‬

‫ﺣﻤﺾ آﻻﻧﺘﻮﻳﻚ‬

‫ﻛﺎرﻣﻮﺳﺘﻴﻦ‪ ‬‬
‫ﻓﻲ ﺣﺎل ﻋﺪم ورود ﻏﻴﺮ ذﻟﻚ ﻓﺈن اﻟﺒﻴﺎﻧﺎت اﻟﻮاردة أﻋﻼه ﻣﻌﻄﺎة ﺑﺎﻟﺤﺎﻟﺔ اﻟﻘﻴﺎﺳﻴﺔ )ﻋﻨﺪ ‪° 25‬س و ‪ 100‬ﻛﻴﻠﻮﺑﺎﺳﻜﺎل(‬
‫ﺗﻌﺪﻳﻞ ﻣﺼﺪري )‪https://ar.wikipedia.org/w/index.php?title=%D9%85%D9%8A%D8%AA%D9%81%D9%88%D8%B1%D9%85%D9%8A%D9%8‬‬
‫‪ -‬ﺗﻌﺪﻳﻞ )‪https://ar.wikipedia.org/w/index.php?title=%D9%85%D9%8A%D8%AA%D9%81%D9%88%D8%B1%‬‬ ‫‪(6&action=edit&section=0‬‬
‫‪(D9%85%D9%8A%D9%86&veaction=edit‬‬
‫‪ ‬‬

‫ّ‬
‫ﺗﺘﻌﻠﻖ ﺑﺎﻟﺴﻼﻣﺔ‪ .‬وﻗﺪ ُﺟ ّﺮب ﻓﻲ أﻣﺮاض أﺧﺮى ﺗﻠﻌﺐ ﺑﻬﺎ ﻣﻘﺎوﻣﺔ‬ ‫ﺗﻢ ﺣﺪّ اﺳﺘﺨﺪاﻣﻪ ﻓﻲ ﺳﻜﺮي اﻟﺤﻮاﻣﻞ ﺑﺴﺒﺐ ﻣﺨﺎوف‬
‫ﻣﻬﻤﺎ‪ .‬ﻳﻌﻤﻞ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻋﻦ ﻃﺮﻳﻖ ﺗﺜﺒﻴﻂ إﻧﺘﺎج اﻟﺠﻠﻮﻛﻮز ﻣﻦ اﻟﻜﺒﺪ‪[9].‬ﻳﺴﺒﺐ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﺑﻌﺾ اﻵﺛﺎر اﻟﻀﺎﺋﺮة‬
‫اﻹﻧﺴﻮﻟﻴﻦ دو ًرا ً‬
‫ﻋﻨﺪﻣﺎ ﻳﻮﺻﻒ ﺑﺸﻜﻞ ﻣﻨﺎﺳﺐ )اﻷﻛﺜﺮ ﺷﻴﻮﻋً ﺎ ﻫﻮ اﺿﻄﺮاب اﻟﺠﻬﺎز اﻟﻬﻀﻤﻲ( وار ُﺗﺒﻂ ﺑﺨﻄﺮ ﻣﻨﺨﻔﺾ ﻟﻨﻘﺺ ﺳﻜﺮ اﻟﺪم‪ .‬ﻳﻤﻜﻦ أن‬
‫ﻳﺸﻜّﻞ اﻟﺤﻤﺎض اﻟﻼﻛﺘﺎﺗﻲ )ارﺗﻔﺎع ﻣﺴﺘﻮى ﺣﻤﺾ اﻟﻠﺒﻨﻴﻚ ﻓﻲ اﻟﺪم( ﻣﺼﺪر ﻗﻠﻖ ﺧﻄﻴﺮ ﻋﻨﺪ ﺗﻨﺎول ﺟﺮﻋﺔ زاﺋﺪة وﻋﻨﺪ وﺻﻔﻪ‬
‫ﻟﻤﺮﺿﻰ ﻣﻊ ﻣﻮاﻧﻊ اﻻﺳﺘﻌﻤﺎل‪.‬‬

‫اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﺟﻴﺪ اﻟﺘﺤﻤﻞ ﺑﺸﻜﻞ ﻋﺎم‪ [10].‬ﺗﺸﻤﻞ اﻵﺛﺎر اﻟﻀﺎرة اﻟﺸﺎﺋﻌﺔ اﻹﺳﻬﺎل واﻟﻐﺜﻴﺎن وآﻻم اﻟﺒﻄﻦ‪ [1].‬وﻟﺪﻳﻪ ﻣﺨﺎﻃﺮ‬
‫ﻣﻨﺨﻔﻀﺔ ﻟﻠﺘﺴﺒﺐ ﻓﻲ اﻧﺨﻔﺎض ﻧﺴﺒﺔ اﻟﺴﻜﺮ ﻓﻲ اﻟﺪم‪ [1].‬ﻳُ ﺼﺪر ﻗﻠﻖ إذا ﺗﻢ اﺳﺘﺨﺪام اﻟﺪواء ﺑﺠﺮﻋﺎت ﻛﺒﻴﺮة ﺟﺪً ا أو ﺗﻢ وﺻﻔﻪ‬
‫ﻟﻸﺷﺨﺎص اﻟﺬﻳﻦ ﻳﻌﺎﻧﻮن ﻣﻦ ﻣﺸﺎﻛﻞ ﺣﺎدة ﻓﻲ اﻟﻜﻠﻰ‪ [12][11].‬ﻻ ﻳﻨﺼﺢ ﺑﺎﺳﺘﺨﺪاﻣﻪ ﻟﻤﻦ ﻳﻌﺎﻧﻮن ﻣﻦ أﻣﺮاض اﻟﻜﺒﺪ‪ .‬اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‬
‫ﻫﻮ ﻋﺎﻣﻞ ﺧﺎﻓﺾ ﻟﻔﺮط ﺳﻜﺮ اﻟﺪم‪ [1].‬وﻫﻮ ﻳﻌﻤﻞ ﻋﻦ ﻃﺮﻳﻖ ﺗﻘﻠﻴﻞ إﻧﺘﺎج اﻟﺠﻠﻮﻛﻮز ﻓﻲ اﻟﻜﺒﺪ‪ ،‬ﻋﻦ ﻃﺮﻳﻖ زﻳﺎدة ﺣﺴﺎﺳﻴﺔ‬
‫اﻟﺤﺮارﻳﺔ‪[15] [14][13].‬‬ ‫اﻷﻧﺴﻮﻟﻴﻦ ﻓﻲ أﻧﺴﺠﺔ اﻟﺠﺴﻢ‪ [1]،‬وزﻳﺎدة إﻓﺮازﻋﺎﻣﻞ اﻟﻨﻤﻮ )‪ ،(GDF15‬ﻣﻤﺎ ﻳﻘﻠﻞ اﻟﺸﻬﻴﺔ وﺗﻨﺎول اﻟﺴﻌﺮات‬

‫اﻛﺘﺸﻒ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻓﻲ ﻋﺎم ‪ [16].1922‬ﺑﺪأ اﻟﻄﺒﻴﺐ اﻟﻔﺮﻧﺴﻲ ﺟﺎن ﺳﺘﻴﺮن اﻟﺪراﺳﺔ ﻋﻠﻰ اﻟﺒﺸﺮ ﻓﻲ اﻟﺨﻤﺴﻴﻨﻴﺎت ﻣﻦ اﻟﻘﺮن‬
‫اﻟﻤﺎﺿﻲ‪ [16].‬ﻗﺪم ﻛﺪواء ﻓﻲ ﻓﺮﻧﺴﺎ ﻋﺎم ‪ 1957‬واﻟﻮﻻﻳﺎت اﻟﻤﺘﺤﺪة ﻋﺎم ‪ [17][1].1995‬وﻫﻮ ﻣﺪرج ﻓﻲ ﻗﺎﺋﻤﺔ ﻣﻨﻈﻤﺔ اﻟﺼﺤﺔ‬
‫اﺳﺘﺨﺪاﻣﺎ ﻟﻤﺮض اﻟﺴﻜﺮي اﻟﺬي ﻳﺆﺧﺬ ﻋﻦ ﻃﺮﻳﻖ اﻟﻔﻢ‪ [16].‬وﻫﻮ‬
‫ً‬ ‫اﻟﻌﺎﻟﻤﻴﺔ ﻟﻸدوﻳﺔ اﻷﺳﺎﺳﻴﺔ‪ [18].‬اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻫﻮ اﻟﺪواء اﻷﻛﺜﺮ‬
 ‫ﻣﺘﻮﻓﺮ ﻛﺪواء ﻋﺎم‪ [1].‬ﻓﻲ ﻋﺎم ‪ ،2018‬ﻛﺎن راﺑﻊ أﻛﺜﺮ اﻷدوﻳﺔ اﻟﻤﻮﺻﻮﻓﺔ ﺷﻴﻮﻋً ﺎ ﻓﻲ اﻟﻮﻻﻳﺎت اﻟﻤﺘﺤﺪة‪ ،‬ﺑﺄﻛﺜﺮ ﻣﻦ ‪ 83‬ﻣﻠﻴﻮن‬
‫ﻃﺒﻴﺔ‪[20][19].‬‬ ‫وﺻﻔﺔ‬

‫ﻋ…‬
‫اﻻﺳﺘﺨﺪاﻣﺎت اﻟﻄﺒﻴﺔ‬

‫ﻳﺴﺘﺨﺪم اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻟﺨﻔﺾ ﻧﺴﺒﺔ اﻟﺴﻜﺮ ﻓﻲ اﻟﺪم ﻟﺪى اﻟﻤﺼﺎﺑﻴﻦ ﺑﺪاء اﻟﺴﻜﺮي اﻟﻨﻤﻂ اﻟﺜﺎﻧﻲ‪ [21].‬ﻛﻤﺎ أﻧﻪ ﻳﺴﺘﺨﺪم ﻛﻌﺎﻣﻞ ﺧﻂ‬
‫اﻟﻤﺒﺎﻳﺾ‪[22][21].‬‬ ‫ﺛﺎﻧﻲ ﻟﻠﻌﻘﻢ ﻋﻨﺪ أوﻟﺌﻚ اﻟﺬﻳﻦ ﻳﻌﺎﻧﻮن ﻣﻦ ﻣﺘﻼزﻣﺔ ﺗﻜﻴﺲ‬

‫داء اﻟﺴﻜﺮي اﻟﻨﻤﻂ اﻟﺜﺎﻧﻲ‬

‫ﻋ…‬
‫ﺗﻮﺻﻲ ﻛﻞ ﻣﻦ ﺟﻤﻌﻴﺔ اﻟﺴﻜﺮي اﻷﻣﺮﻳﻜﻴﺔ واﻟﻜﻠﻴﺔ اﻷﻣﺮﻳﻜﻴﺔ ﻟﻸﻃﺒﺎء ﺑﺎﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻛﻌﺎﻣﻞ ﺧﻂ أول ﻟﻌﻼج اﻟﺴﻜﺮي اﻟﻨﻤﻂ‬
‫اﻟﻔﻢ‪[26].‬‬ ‫اﻟﺜﺎﻧﻲ‪[25][24][23].‬إﻧﻪ ﻓﻌﺎل ﻣﺜﻞ رﻳﺒﺎﻏﻠﻴﻨﻴﺪ وأﻛﺜﺮ ﻓﻌﺎﻟﻴﺔ ﻣﻦ ﺟﻤﻴﻊ أدوﻳﺔ داء اﻟﺴﻜﺮي ﻣﻦ اﻟﻨﻮع اﻟﺜﺎﻧﻲ ﻋﻦ ﻃﺮﻳﻖ‬

‫ﻋ…‬
‫اﻟﻔﻌﺎﻟﻴﺔ‬

‫ﻗﺪﻣﺖ اﻟﺪراﺳﺔ اﻻﺳﺘﺒﺎﻗﻴﺔ ﻟﻤﺮض اﻟﺴﻜﺮي ﻓﻲ اﻟﻤﻤﻠﻜﺔ اﻟﻤﺘﺤﺪة‪ ،‬وﻫﻲ ﺗﺠﺮﺑﺔ ﺳﺮﻳﺮﻳﺔ ﻛﺒﻴﺮة أﺟﺮﻳﺖ ﻓﻲ ‪ ،1990-1980‬دﻟﻴ ً‬
‫ﻼ‬
‫ﻋﻠﻰ أن اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻗﻠﻞ ﻣﻦ ﻣﻌﺪل اﻟﻨﺘﺎﺋﺞ اﻟﺴﻠﺒﻴﺔ ﻟﻠﻘﻠﺐ واﻷوﻋﻴﺔ اﻟﺪﻣﻮﻳﺔ ﻓﻲ اﻟﻤﺮﺿﻰ اﻟﺬﻳﻦ ﻳﻌﺎﻧﻮن ﻣﻦ زﻳﺎدة اﻟﻮزن ﻣﻊ داء‬
‫اﻟﺴﻜﺮي ﻣﻦ اﻟﻨﻮع ‪ 2‬ﻣﻘﺎرﻧﺔ ﺑﺎﻟﻌﻮاﻣﻞ اﻷﺧﺮى اﻟﺨﺎﻓﻀﺔ ﻟﻔﺮط ﺳﻜﺮ اﻟﺪم‪ [27].‬وﻣﻊ ذﻟﻚ‪ ،‬ﻓﺈن اﻷدﻟﺔ اﻟﻤﺘﺮاﻛﻤﺔ ﻣﻦ ﺗﺠﺎرب أﺧﺮى‬
‫وأﻛﺜﺮ ﺣﺪاﺛﺔ‪ ،‬ﻗﻠﻠﺖ ﻣﻦ اﻟﺜﻘﺔ ﻓﻲ ﻓﻌﺎﻟﻴﺔ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻟﻠﻮﻗﺎﻳﺔ ﻣﻦ أﻣﺮاض اﻟﻘﻠﺐ واﻷوﻋﻴﺔ اﻟﺪﻣﻮﻳﺔ‪ [29][28].‬ﺗﺘﺤﺴﻦ اﻟﻨﺘﺎﺋﺞ‬
‫اﻟﻤﺰﻣﻨﺔ‪[30].‬‬ ‫ﺣﺘﻰ ﻋﻨﺪ اﻟﻤﺼﺎﺑﻴﻦ ﺑﺪرﺟﺔ ﻣﻌﻴﻨﺔ ﻣﻦ أﻣﺮاض اﻟﻜﻠﻰ أو ﻗﺼﻮر اﻟﻘﻠﺐ أو أﻣﺮاض اﻟﻜﺒﺪ‬

‫اﻹرﺷﺎدات اﻟﻌﻼﺟﻴﺔ ﻟﻠﺠﻤﻌﻴﺎت اﻟﻤﻬﻨﻴﺔ اﻟﻜﺒﺮى‪ ،‬ﺑﻤﺎ ﻓﻲ ذﻟﻚ اﻟﺮاﺑﻄﺔ اﻷوروﺑﻴﺔ ﻟﺪراﺳﺔ ﻣﺮض اﻟﺴﻜﺮي‪ ،‬واﻟﺠﻤﻌﻴﺔ اﻷوروﺑﻴﺔ‬
‫ﻷﻣﺮاض اﻟﻘﻠﺐ‪ ،‬واﻟﺠﻤﻌﻴﺔ اﻷﻣﺮﻳﻜﻴﺔ ﻟﻤﺮض اﻟﺴﻜﺮي‪ ،‬ﺗﺼﻒ اﻵن اﻟﺪﻟﻴﻞ ﻋﻠﻰ اﻟﻔﻮاﺋﺪ اﻟﻘﻠﺒﻴﺔ اﻟﻮﻋﺎﺋﻴﺔ ﻟﻠﻤﻴﺘﻔﻮرﻣﻴﻦ ﺑﺎﻋﺘﺒﺎرﻫﺎ‬
‫ﻣﻠﺘﺒﺴﺔ‪[31][24].‬‬

‫ﻓﻲ ﻋﺎم ‪ ،2017‬ﺗﻢ ﺗﺤﺪﻳﺚ إرﺷﺎدات اﻟﻜﻠﻴﺔ اﻷﻣﺮﻳﻜﻴﺔ ﻟﻸﻃﺒﺎء ﻟﻠﺘﻌﺮف ﻋﻠﻰ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﺑﺎﻋﺘﺒﺎره اﻟﻌﻼج اﻷول ﻟﻤﺮض اﻟﺴﻜﺮي‬
‫ﻣﺒﺪﺋﻴﺎ ﻋﻠﻰ‬
‫ً‬ ‫ﻣﻦ اﻟﻨﻮع ‪ .2‬ﺗﺤﻞ ﻫﺬه اﻹرﺷﺎدات ﻣﺤﻞ اﻟﻤﺮاﺟﻌﺎت اﻟﺴﺎﺑﻘﺔ‪ .‬ﻋﻠﻰ ﺳﺒﻴﻞ اﻟﻤﺜﺎل‪ ،‬وﺟﺪت ﻣﺮاﺟﻌﺔ ﻋﺎم ‪ً 2014‬‬
‫دﻟﻴﻼ‬
‫أن اﻷﺷﺨﺎص اﻟﺬﻳﻦ ﻋﻮﻟﺠﻮا ﺑﺎﻟﺴﻠﻔﻮﻧﻴﻞ ﻳﻮرﻳﺎ ﻛﺎﻧﻮا أﻛﺜﺮ ﻋﺮﺿﺔ ﻟﺨﻄﺮ اﻹﺻﺎﺑﺔ ﺑﺎﻧﺨﻔﺎض ﺷﺪﻳﺪ ﻓﻲ ﻧﺴﺒﺔ اﻟﺴﻜﺮ ﻓﻲ اﻟﺪم )‪RR‬‬
‫‪ ،(5.64‬ﻋﻠﻰ اﻟﺮﻏﻢ ﻣﻦ أن ﻣﺨﺎﻃﺮ اﻹﺻﺎﺑﺔ ﺑﺄﻣﺮاض اﻟﻘﻠﺐ واﻷوﻋﻴﺔ اﻟﺪﻣﻮﻳﺔ ﻏﻴﺮ اﻟﻤﻤﻴﺘﺔ ﻛﺎﻧﺖ أﻗﻞ ﻣﻦ ﻣﺨﺎﻃﺮ أوﻟﺌﻚ اﻟﺬﻳﻦ‬
‫ﻋﻮﻟﺠﻮا ﺑﺎﻟﻤﻴﺘﻔﻮرﻣﻴﻦ )‪ .(RR 0.67‬ﻟﻢ ﺗﺘﻮﻓﺮ ﺑﻴﺎﻧﺎت ﻛﺎﻓﻴﺔ ﻓﻲ ذﻟﻚ اﻟﻮﻗﺖ ﻟﺘﺤﺪﻳﺪ اﻟﺨﻄﺮ اﻟﻨﺴﺒﻲ ﻟﻠﻮﻓﺎة أو اﻟﻮﻓﺎة ﻣﻦ أﻣﺮاض‬
‫اﻟﻘﻠﺐ‪[32].‬‬

‫ﻳﻘﻠﻞ اﺳﺘﺨﺪام اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻣﻦ وزن اﻟﺠﺴﻢ ﻟﺪى اﻷﺷﺨﺎص اﻟﻤﺼﺎﺑﻴﻦ ﺑﺪاء اﻟﺴﻜﺮي ﻣﻦ اﻟﻨﻮع ‪[34][33]،2‬ﻋﻠﻰ ﻋﻜﺲ اﻟﺴﻠﻔﻮﻧﻴﻞ‬
‫ﻳﻮرﻳﺎ‪ ،‬اﻟﺬي ﻳﺮﺗﺒﻂ ﺑﺰﻳﺎدة اﻟﻮزن‪ [34].‬ﺗﻈﻬﺮ ﺑﻌﺾ اﻷدﻟﺔ أن اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻳﺮﺗﺒﻂ ﺑﻔﻘﺪان اﻟﻮزن ﻋﻨﺪ ﻣﻦ ﻳﻌﺎﻧﻮن ﻣﻦ اﻟﺴﻤﻨﺔ ﻓﻲ‬
‫ﺣﺎﻟﺔ ﻋﺪم وﺟﻮد ﻣﺮض اﻟﺴﻜﺮي‪ [36][35].‬ﻟﺪى اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻣﺨﺎﻃﺮ أﻗﻞ ﻟﻺﺻﺎﺑﺔ ﺑﻨﻘﺺ اﻟﺴﻜﺮ ﻓﻲ اﻟﺪم ﻣﻘﺎرﻧﺔ ﺑﺎﻟﺴﻠﻔﻮﻧﻴﻞ‬
‫ﻳﻮرﻳﺎ‪[38] [37]،‬ﻋﻠﻰ اﻟﺮﻏﻢ ﻣﻦ ﺣﺪوث ﻧﻘﺺ اﻟﺴﻜﺮ ﻓﻲ اﻟﺪم ﺑﺸﻜﻞ ﻏﻴﺮ ﺷﺎﺋﻊ أﺛﻨﺎء اﻟﺘﻤﺮﻳﻨﺎت اﻟﺮﻳﺎﺿﻴﺔ اﻟﺸﺪﻳﺪة‪ ،‬أو ﻧﻘﺺ‬
‫اﻟﺴﻌﺮات اﻟﺤﺮارﻳﺔ‪ ،‬أو ﻋﻨﺪ اﺳﺘﺨﺪاﻣﻪ ﻣﻊ ﻋﻮاﻣﻞ أﺧﺮى ﻟﺨﻔﺾ ﻧﺴﺒﺔ اﻟﺴﻜﺮ ﻓﻲ اﻟﺪم‪ [40][39].‬ﻳﻘﻠﻞ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﺑﺸﻜﻞ ﻣﺘﻮاﺿﻊ‬
‫]‪[38][37‬‬
‫ﻣﻦ ﻣﺴﺘﻮﻳﺎت اﻟﺒﺮوﺗﻴﻦ اﻟﺪﻫﻨﻲ ﻣﻨﺨﻔﺾ اﻟﻜﺜﺎﻓﺔ واﻟﺪﻫﻮن اﻟﺜﻼﺛﻴﺔ‪.‬‬

‫ﻣﺘﻼزﻣﺔ ﺗﻜﻴﺲ اﻟﻤﺒﺎﻳﺾ‬

‫ﻋ…‬
‫ﻓﻲ أوﻟﺌﻚ اﻟﺬﻳﻦ ﻳﻌﺎﻧﻮن ﻣﻦ ﻣﺘﻼزﻣﺔ ﺗﻜﻴﺲ اﻟﻤﺒﺎﻳﺾ )‪ ،(PCOS‬ﺗﻈﻬﺮ أدﻟﺔ أوﻟﻴﺔ أن اﺳﺘﺨﺪام اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻳﺰﻳﺪ ﻣﻦ ﻣﻌﺪل‬
‫اﻟﻤﻮاﻟﻴﺪ اﻷﺣﻴﺎء‪ [41].‬وﻫﺬا ﻳﺸﻤﻞ أوﻟﺌﻚ اﻟﺬﻳﻦ ﻟﻢ ﻳﺘﻤﻜﻨﻮا ﻣﻦ اﻟﺤﻤﻞ ﻣﻊ ﻋﻘﺎر ﻛﻠﻮﻣﻴﻔﻴﻦ‪ [42].‬ﻻ ﻳﺒﺪو أن اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻳﻐﻴﺮ ﻣﻦ‬
‫أﻳﻀﺎ أﺛﻨﺎء اﻟﺤﻤﻞ وﻓﻲ اﻷﺷﺨﺎص ﻏﻴﺮ اﻟﺤﻮاﻣﻞ اﻟﻤﺼﺎﺑﻴﻦ ﺑﻤﺘﻼزﻣﺔ‬ ‫ﺧﻄﺮ اﻹﺟﻬﺎض‪ [41].‬ﻋﺜﺮ ﻋﻠﻰ ﻋﺪد ﻣﻦ اﻟﻔﻮاﺋﺪ اﻷﺧﺮى ً‬
‫ﺗﻜﻴﺲ اﻟﻤﺒﺎﻳﺾ‪ [44][43].‬ﻓﻲ ﻣﺮاﺟﻌﺔ ﻣﺤﺪﺛﺔ ﻟـﻜﻮﺷﺮان )‪ (2020‬ﺣﻮل اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻣﻘﺎﺑﻞ اﻟﺪواء اﻟﻮﻫﻤﻲ أو ﻋﺪم اﻟﻌﻼج ﻗﺒﻞ أو‬
‫أﺛﻨﺎء اﻟﺘﻠﻘﻴﺢ اﻻﺻﻄﻨﺎﻋﻲ اواﻟﺤﻘﻦ اﻟﻤﺠﻬﺮي ﻟﺪى اﻟﻨﺴﺎء اﻟﻤﺼﺎﺑﺎت ﺑﻤﺘﻼزﻣﺔ ﺗﻜﻴﺲ اﻟﻤﺒﺎﻳﺾ‪ ،‬ﻟﻢ ﻳﺘﻢ اﻟﻌﺜﻮر ﻋﻠﻰ دﻟﻴﻞ ﻗﺎﻃﻊ‬
‫ﻋﻠﻰ ﻣﻌﺪﻻت اﻟﻤﻮاﻟﻴﺪ اﻟﺤﻴﺔ اﻟﻤﺤﺴﻨﺔ‪[45].‬ﻓﻲ ﺑﺮوﺗﻮﻛﻮﻻت ﻧﺎﻫﺾ اﻟﻬﺮﻣﻮن اﻟﻤﻄﻠﻖ ﻟﻤﻮﺟﻬﺔ اﻟﻐﺪد اﻟﺘﻨﺎﺳﻠﻴﺔ اﻟﻄﻮﻳﻠﺔ ﻛﺎن ﻫﻨﺎك‬
‫اﻟﺴﺮﻳﺮي‪[45].‬‬ ‫ﻋﺪم ﻳﻘﻴﻦ ﻓﻲ اﻷدﻟﺔ ﻋﻠﻰ ﻣﻌﺪﻻت اﻟﻤﻮاﻟﻴﺪ اﻟﺤﻴﺔ اﻟﻤﺤﺴﻨﺔ وﻟﻜﻦ ﻳﻤﻜﻦ أن ﺗﻜﻮن ﻫﻨﺎك زﻳﺎدات ﻓﻲ ﻣﻌﺪل اﻟﺤﻤﻞ‬
‫ﺑﺎﺧﺘﺼﺎر ﺑﺮوﺗﻮﻛﻮﻻت ﻣﻀﺎدات اﻟﻬﺮﻣﻮن اﻟﻤﻄﻠﻖ ﻟﻤﻮاﺟﻬﺔ اﻟﻐﺪد اﻟﺘﻨﺎﺳﻠﻴﺔ ﻗﺪ ﻳﻘﻠﻞ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻣﻌﺪﻻت اﻟﻤﻮاﻟﻴﺪ اﻷﺣﻴﺎء ﻣﻊ‬
‫ﻋﺪم اﻟﻴﻘﻴﻦ ﺑﺸﺄن ﺗﺄﺛﻴﺮه ﻋﻠﻰ ﻣﻌﺪل اﻟﺤﻤﻞ اﻟﺴﺮﻳﺮي‪ [45].‬ﻗﺪ ﻳﺆدي اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ إﻟﻰ اﻧﺨﻔﺎض ﻓﻲ ﻣﺘﻼزﻣﺔ ﻓﺮط ﺗﻨﺒﻴﻪ اﻟﻤﺒﻴﺾ‬
‫وﻟﻜﻦ ﻳﻤﻜﻦ أن ﻳﺄﺗﻲ ﻣﻊ ﺗﻜﺮار أﻛﺒﺮ ﻟﻶﺛﺎر اﻟﺠﺎﻧﺒﻴﺔ‪ [45].‬ﻛﺎن ﻫﻨﺎك ﻋﺪم ﻳﻘﻴﻦ ﺑﺸﺄن ﺗﺄﺛﻴﺮ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻋﻠﻰ اﻹﺟﻬﺎض‪ [45].‬ﻻ ﺗﺪﻋﻢ‬
‫اﻟﺒﺪﻳﻨﺎت‪[46].‬‬ ‫اﻷدﻟﺔ اﻻﺳﺘﺨﺪام اﻟﻌﺎم أﺛﻨﺎء اﻟﺤﻤﻞ ﻟﺘﺤﺴﻴﻦ ﻧﺘﺎﺋﺞ اﻷﻣﻬﺎت واﻟﺮﺿﻊ ﻋﻨﺪ اﻟﻨﺴﺎء‬

‫أوﺻﻰ اﻟﻤﻌﻬﺪ اﻟﻮﻃﻨﻲ ﻟﻠﺼﺤﺔ واﻟﺘﻔﻮق اﻟﺴﺮﻳﺮي ﻓﻲ اﻟﻤﻤﻠﻜﺔ اﻟﻤﺘﺤﺪة ﻓﻲ ﻋﺎم ‪ 2004‬ﺑﺈﻋﻄﺎء اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻟﻠﻨﺴﺎء اﻟﻤﺼﺎﺑﺎت‬
‫اﻟﻨﺘﺎﺋﺞ‪[47].‬‬ ‫ﺑﻤﺘﻼزﻣﺔ ﺗﻜﻴﺲ اﻟﻤﺒﺎﻳﺾ وﻣﺆﺷﺮ ﻛﺘﻠﺔ اﻟﺠﺴﻢ ﻓﻮق ‪ 25‬ﻟﻺﺑﺎﺿﺔ واﻟﻌﻘﻢ ﻋﻨﺪﻣﺎ ﺗﻔﺸﻞ اﻟﻌﻼﺟﺎت اﻷﺧﺮى ﻓﻲ ﺗﺤﻘﻴﻖ‬
‫ﻻ ﺗﻮﺻﻲ إرﺷﺎدات اﻟﻤﻤﺎرﺳﺔ اﻟﺴﺮﻳﺮﻳﺔ اﻟﺒﺮﻳﻄﺎﻧﻴﺔ واﻟﺪوﻟﻴﺔ ﺑﺎﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻛﻌﻼج ﻣﻦ اﻟﺪرﺟﺔ اﻷوﻟﻰ أو ﻻ ﺗﻮﺻﻲ ﺑﻪ ﻋﻠﻰ‬
‫اﻹﻃﻼق‪ [48]،‬ﺑﺎﺳﺘﺜﻨﺎء اﻟﻨﺴﺎء اﻟﻼﺗﻲ ﻳﻌﺎﻧﻴﻦ ﻣﻦ ﻋﺪم ﺗﺤﻤﻞ اﻟﺠﻠﻮﻛﻮز‪ [49].‬ﺗﺸﻴﺮ اﻟﺪﻻﺋﻞ اﻹرﺷﺎدﻳﺔ إﻟﻰ ﻋﻘﺎر ﻛﻠﻮﻣﻴﻔﻴﻦ )دواء‬
‫ﻣﻌﺎﻟﺞ ﻟﻠﻌﻘﻢ( ﻛﺨﻴﺎر ﻋﻼﺟﻲ أول‪ ،‬وﺗﺆﻛﺪ ﻋﻠﻰ ﺗﻌﺪﻳﻞ ﻧﻤﻂ اﻟﺤﻴﺎة ﺑﺸﻜﻞ ﻣﺴﺘﻘﻞ ﻋﻦ اﻟﻌﻼج اﻟﻄﺒﻲ‪ .‬ﻳﻘﻠﻞ ﻋﻼج اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻣﻦ‬
‫ً‬
‫ﺿﻌﻔﺎ ﻓﻲ ﺗﺤﻤﻞ‬ ‫ﺧﻄﺮ اﻹﺻﺎﺑﺔ ﺑﺪاء اﻟﺴﻜﺮي ﻣﻦ اﻟﻨﻮع ‪ 2‬ﻟﺪى اﻟﻨﺴﺎء اﻟﻤﺼﺎﺑﺎت ﺑﻤﺘﻼزﻣﺔ ﺗﻜﻴﺲ اﻟﻤﺒﺎﻳﺾ اﻟﻼﺗﻲ أﻇﻬﺮن‬
‫اﻷﺳﺎس‪[51][50].‬‬ ‫اﻟﺠﻠﻮﻛﻮز ﻋﻨﺪ ﺧﻂ‬

‫ﻋ…‬
‫داء اﻟﺴﻜﺮي واﻟﺤﻤﻞ‬

‫وﺟﺪت ﻣﺮاﺟﻌﺔ ﺷﺎﻣﻠﺔ ﻻﺳﺘﺨﺪام اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ أﺛﻨﺎء اﻟﺤﻤﻞ ﻣﻘﺎرﻧﺔ ﺑﺎﻷﻧﺴﻮﻟﻴﻦ وﺣﺪه أﻣﺎ ًﻧﺎ ﺟﻴﺪً ا ﻋﻠﻰ اﻟﻤﺪى اﻟﻘﺼﻴﺮ ﻟﻜﻞ ﻣﻦ‬
‫اﻷم واﻟﻄﻔﻞ‪ ،‬وﻟﻜﻦ اﻷﻣﺎن ﻏﻴﺮ واﺿﺢ ﻋﻠﻰ اﻟﻤﺪى اﻟﻄﻮﻳﻞ‪ [52].‬وﺟﺪت اﻟﻌﺪﻳﺪ ﻣﻦ اﻟﺪراﺳﺎت اﻟﻘﺎﺋﻤﺔ ﻋﻠﻰ اﻟﻤﻼﺣﻈﺔ واﻟﺘﺠﺎرب‬
‫اﻟﻌﺸﻮاﺋﻴﺔ ذات اﻟﺸﻮاﻫﺪ أن اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻓﻌﺎل وآﻣﻦ ﻣﺜﻞ اﻷﻧﺴﻮﻟﻴﻦ ﻹدارة ﺳﻜﺮي اﻟﺤﻤﻞ‪ [53][53].‬وﻣﻊ ذﻟﻚ‪ ،‬ﻓﻘﺪ أﺛﻴﺮت اﻟﻌﺪﻳﺪ‬
‫ﻣﻦ اﻟﻤﺨﺎوف وﻫﻨﺎك ﻧﻘﺺ ﻓﻲ اﻷدﻟﺔ ﻋﻠﻰ ﺳﻼﻣﺔ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻋﻠﻰ اﻟﻤﺪى اﻟﻄﻮﻳﻞ ﻟﻜﻞ ﻣﻦ اﻷم واﻟﻄﻔﻞ‪ [54].‬ﺑﺎﻟﻤﻘﺎرﻧﺔ ﻣﻊ‬
‫اﻷﻧﺴﻮﻟﻴﻦ‪ ،‬ﻓﺈن اﻟﻨﺴﺎء اﻟﻤﺼﺎﺑﺎت ﺑﺴﻜﺮي اﻟﺤﻤﻞ اﻟﻤﻌﺎﻟﺠﺎت ﺑﺎﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻳﻜﺘﺴﺒﻦ وز ًﻧﺎ أﻗﻞ وﻳﻘﻞ اﺣﺘﻤﺎل اﻹﺻﺎﺑﺔ ﺑﺘﺴﻤﻢ‬
‫اﻟﺤﻤﻞ أﺛﻨﺎء اﻟﺤﻤﻞ‪[55] [54].‬اﻷﻃﻔﺎل اﻟﺬﻳﻦ ﻳﻮﻟﺪون ﻟﻨﺴﺎء ﻋﻮﻟﺠﻦ ﺑﺎﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻟﺪﻳﻬﻢ دﻫﻮن ﺣﺸﻮﻳﺔ أﻗﻞ ‪ ،‬وﻫﺬا ﻗﺪ ﻳﺠﻌﻠﻬﻢ‬
‫أﻗﻞ ﻋﺮﺿﺔ ﻟﻤﻘﺎوﻣﺔ اﻷﻧﺴﻮﻟﻴﻦ ﻓﻲ وﻗﺖ ﻻﺣﻖ ﻣﻦ اﻟﺤﻴﺎة‪ [56].‬أدى اﺳﺘﺨﺪام اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻟﺴﻜﺮي اﻟﺤﻤﻞ إﻟﻰ أﻃﻔﺎل أﺻﻐﺮ‬
‫ً‬
‫ﻣﻘﺎرﻧﺔ ﺑﺎﻟﻌﻼج ﺑﺎﻷﻧﺴﻮﻟﻴﻦ‪ .‬وﻣﻊ ذﻟﻚ‪ ،‬ﻋﻠﻰ اﻟﺮﻏﻢ ﻣﻦ اﻧﺨﻔﺎض اﻟﻮزن ﻋﻨﺪ اﻟﻮﻻدة ﻓﻲ اﻟﺒﺪاﻳﺔ‪ ،‬ﻓﺈن اﻷﻃﻔﺎل اﻟﺬﻳﻦ ﺗﻌﺮﺿﻮا‬
‫ﻟﻠﻤﻴﺘﻔﻮرﻣﻴﻦ أﺛﻨﺎء اﻟﺤﻤﻞ ﻗﺪ ﺗﺴﺎرع ﻧﻤﻮﻫﻢ ﺑﻌﺪ اﻟﻮﻻدة‪ ،‬وﻛﺎﻧﻮا أﺛﻘﻞ ﻓﻲ ﻣﻨﺘﺼﻒ اﻟﻄﻔﻮﻟﺔ ﻣﻦ أوﻟﺌﻚ اﻟﺬﻳﻦ ﺗﻌﺮﺿﻮا ﻟﻸﻧﺴﻮﻟﻴﻦ‬
 ‫أﺛﻨﺎء اﻟﺤﻤﻞ‪ .‬ﻫﺬا اﻟﻨﻤﻂ ﻣﻦ اﻧﺨﻔﺎض اﻟﻮزن اﻷوﻟﻲ ﻋﻨﺪ اﻟﻮﻻدة ﻣﺘﺒﻮﻋً ﺎ ﺑﻨﻤﻮ اﻟﻠﺤﺎق ﺑﺎﻟﺮﻛﺐ اﻟﺬي ﻳﺘﺠﺎوز اﻷﻃﻔﺎل اﻟﻤﻘﺎرن ﻗﺪ‬
‫اﻟﻄﻮﻳﻞ‪[57].‬‬ ‫ارﺗﺒﻂ ﺑﺄﻣﺮاض اﻟﻘﻠﺐ واﻷوﻋﻴﺔ اﻟﺪﻣﻮﻳﺔ ﻋﻠﻰ اﻟﻤﺪى‬

‫ﺗﻐﻴﺮ اﻟﻮزن‬
‫ﻋ…‬
‫ﻋﺎدة ﻣﺎ ﻳﺮﺗﺒﻂ اﺳﺘﺨﺪام اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﺑﻔﻘﺪان اﻟﻮزن‪ [58].‬ﻳﺒﺪو أﻧﻪ آﻣﻦ وﻓﻌﺎل ﻓﻲ ﻣﻮاﺟﻬﺔ زﻳﺎدة اﻟﻮزن اﻟﺘﻲ ﺗﺴﺒﺒﻬﺎ اﻷدوﻳﺔ‬
‫اﻟﻤﻀﺎدة ﻟﻠﺬﻫﺎن أوﻻﻧﺰاﺑﻴﻦ وﻛﻠﻮزاﺑﻴﻦ )دواء ﻣﻬﺪئ(‪[60][59].‬ﻋﻠﻰ اﻟﺮﻏﻢ ﻣﻦ وﺟﻮد اﻧﻌﻜﺎس ﺑﺴﻴﻂ ﻓﻲ زﻳﺎدة اﻟﻮزن اﻟﻤﺮﺗﺒﻄﺔ‬
‫ﻗﻴﻤﺔ‪[61].‬‬ ‫ﺑﺎﻟﻜﻠﻮزاﺑﻴﻦ ﻣﻊ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‪ ،‬ﻓﺈن اﻟﻮﻗﺎﻳﺔ اﻷوﻟﻴﺔ ﻣﻦ زﻳﺎدة اﻟﻮزن ﺗﻜﻮن أﻛﺜﺮ‬

‫ﻋ…‬
‫اﺳﺘﺨﺪم ﻣﻊ اﻷﻧﺴﻮﻟﻴﻦ‬

‫ﻗﺪ ﻳﻘﻠﻞ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻣﻦ ﻣﺘﻄﻠﺒﺎت اﻷﻧﺴﻮﻟﻴﻦ ﻓﻲ ﻣﺮض اﻟﺴﻜﺮي اﻟﻨﻤﻂ اﻷول‪ ،‬وإن ﻛﺎن ذﻟﻚ ﻣﻊ زﻳﺎدة ﺧﻄﺮ اﻹﺻﺎﺑﺔ ﺑﻨﻘﺺ‬
‫اﻟﺪم‪[62].‬‬ ‫اﻟﺴﻜﺮ ﻓﻲ‬

‫ﻋ…‬
‫ﻣﻮاﻧﻊ اﻻﺳﺘﻌﻤﺎل‬

‫ﻳﻤﻨﻊ اﺳﺘﺨﺪم اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻓﻲ اﻷﺷﺨﺎص اﻟﺬﻳﻦ ﻳﻌﺎﻧﻮن ﻣﻦ‪:‬‬

‫‪[63](2‬‬ ‫ﺿﻌﻒ ﻛﻠﻮي ﺣﺎد )ﻣﻌﺪل اﻟﺘﺮﺷﻴﺢ اﻟﻜﺒﻴﺒﻲ اﻟﻤﻘﺪر )‪ (eGFR‬أﻗﻞ ﻣﻦ ‪ 30‬ﻣﻞ ‪ /‬دﻗﻴﻘﺔ ‪ 1.73 /‬م‬
‫ﻟﻠﻤﻴﺘﻔﻮرﻣﻴﻦ‪[63].‬‬ ‫ﻓﺮط اﻟﺤﺴﺎﺳﻴﺔ اﻟﻤﻌﺮوف‬
‫اﻟﺤﻤﺎض اﻷﻳﻀﻲ اﻟﺤﺎد أو اﻟﻤﺰﻣﻦ‪ ،‬ﺑﻤﺎ ﻓﻲ ذﻟﻚ اﻟﺤﻤﺎض اﻟﻜﻴﺘﻮﻧﻲ اﻟﺴﻜﺮي )ﻣﻦ ﻣﺮض اﻟﺴﻜﺮي ﻏﻴﺮ اﻟﻤﻨﻀﺒﻂ( ]‪ [63‬ﻣﻊ أو‬
‫ﻏﻴﺒﻮﺑﺔ‪[64].‬‬ ‫ﺑﺪون‬
‫ﻳﺘﻢ إﻋﻄﺎء ﺗﺤﺬﻳﺮات ً‬
‫أﻳﻀﺎ ﻓﻴﻤﺎ ﻳﺘﻌﻠﻖ ﺑﺎﺳﺘﺨﺪام اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻓﻲ ﺣﺎﻻت اﻟﻘﺼﻮر اﻟﻜﻠﻮي اﻷﻗﻞ ﺧﻄﻮرة ‪ ،‬واﻷﺷﺨﺎص اﻟﺬﻳﻦ‬
‫ﻋﺎﻣﺎ أو أﻛﺜﺮ ‪ ،‬وﺣﺎﻻت ﻧﻘﺺ اﻷﻛﺴﺠﻴﻦ )ﻋﻠﻰ ﺳﺒﻴﻞ اﻟﻤﺜﺎل ‪ ،‬ﻗﺼﻮر اﻟﻘﻠﺐ اﻻﺣﺘﻘﺎﻧﻲ اﻟﺤﺎد( ‪ ،‬واﻹﻓﺮاط ﻓﻲ‬
‫ﺗﺒﻠﻎ أﻋﻤﺎرﻫﻢ ‪ً 65‬‬
‫ﺗﻨﺎول اﻟﻜﺤﻮل‪ ،‬واﻻﺧﺘﻼل اﻟﻜﺒﺪي‪ ،‬واﻻﺳﺘﺨﺪام اﻟﻤﺘﺰاﻣﻦ ﻟﺒﻌﺾ اﻷدوﻳﺔ )ﻣﺜﻞ اﻷﻧﻬﻴﺪراز اﻟﻜﺮﺑﻮﻧﻲ ﻣﺜﺒﻄﺎت ﻣﺜﻞ ﺗﻮﺑﻴﺮاﻣﻴﺖ(‪،‬‬
‫واﻟﺠﺮاﺣﺔ‪ ،‬وﻏﻴﺮﻫﺎ ﻣﻦ اﻹﺟﺮاءات‪ ،‬أو ﻓﻲ اﻷﺷﺨﺎص اﻟﺬﻳﻦ ﺧﻀﻌﻮا ﻟﺪراﺳﺔ إﺷﻌﺎﻋﻴﺔ ﻣﻊ إﻋﻄﺎء ﻋﺎﻣﻞ ﺗﺒﺎﻳﻦ ﻣﻌﺎﻟﺞ‬
‫]ﺑﺤﺎﺟﺔ ﻟﻤﺼﺪر ﻃﺒﻲ[‬
‫ﺑﺎﻟﻴﻮد‪.‬‬

‫ﻳﻮﺻﻰ ﺑﺈﻳﻘﺎف اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻣﺆﻗﺘً ﺎ ﻗﺒﻞ أي إﺟﺮاء ﻳﺘﻀﻤﻦ اﺳﺘﺨﺪام ﻋﻮاﻣﻞ اﻟﺘﺒﺎﻳﻦ ﺑﺎﻟﻴﻮد )ﻣﺜﻞ اﻟﺘﺼﻮﻳﺮ اﻟﻤﻘﻄﻌﻲ اﻟﻤﺤﻮﺳﺐ أو‬
‫ﺗﺼﻮﻳﺮ اﻷوﻋﻴﺔ اﻟﺪﻣﻮﻳﺔ( ﺑﺴﺒﺐ زﻳﺎدة ﺧﻄﺮ اﻹﺻﺎﺑﺔ ﺑﺎﻟﺤﻤﺎض اﻟﻠﺒﻨﻲ اﻟﻨﺎﺗﺞ ﻋﻦ ﺿﻌﻒ وﻇﺎﺋﻒ اﻟﻜﻠﻰ‪[66][65].‬ﻳﻤﻜﻦ اﺳﺘﺌﻨﺎف‬
‫اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﺑﻌﺪ ﻳﻮﻣﻴﻦ ﺑﻌﺪ إدارة اﻟﺘﺒﺎﻳﻦ‪ ،‬إذا ﻛﺎﻧﺖ وﻇﻴﻔﺔ اﻟﻜﻠﻰ ﻛﺎﻓﻴﺔ وﻣﺴﺘﻘﺮة‪.‬‬

‫اﻷﻋﺮاض اﻟﺠﺎﻧﺒﻴﺔ‬

‫ﺗﻬﻴﺞ اﻟﺠﻬﺎز اﻟﻬﻀﻤﻲ‪ ،‬ﺑﻤﺎ ﻓﻲ ذﻟﻚ اﻹﺳﻬﺎل واﻟﺘﺸﻨﺠﺎت واﻟﻐﺜﻴﺎن‬ ‫ً‬

‫اﻧﺘﺸﺎرا ﻫﻲ ّ‬ ‫أﺷﻬﺮ اﻷﻋﺮاض اﻟﺠﺎﻧﺒﻴﺔ ﻟﻠﻤﻴﺘﻔﻮرﻣﻴﻦ واﻷﻛﺜﺮ‬
‫اﻟﻤ ِﻌﺪﻳّ ﺔ اﻟﻤﻌﻮﻳﺔ )اﻷﻋﺮاض‬
‫واﻟﻘﻲء وزﻳﺎدة اﻧﺘﻔﺎخ اﻟﺒﻄﻦ‪ .‬ﺣﻴﺚ ﻳﺮﺗﺒﻂ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﺑﺸﻜﻞ أﻛﺜﺮ ﺷﻴﻮﻋً ﺎ ﺑﺎﻷﻋﺮاض اﻟﺠﺎﻧﺒﻴﺔ َ‬
 ‫اﻟﺠﺎﻧﺒﻴﺔ اﻟﺘﻲ ﺗﺮﺗﺒﻂ ﺑﺎﻟﺠﻬﺎز اﻟﻬﻀﻤﻲ( ﻣﻦ ﻣﻌﻈﻢ اﻷدوﻳﺔ اﻷﺧﺮى اﻟﻤﻀﺎدة ﻟﻤﺮض اﻟﺴﻜﺮ‪ [67].‬أﺧﻄﺮ ﻋﺮض ﺟﺎﻧﺒﻲ ﺿﺎر ﻣﺤﺘﻤﻞ‬
‫ﻟﻠﻤﻴﺘﻔﻮرﻣﻴﻦ ﻫﻮ اﻟﺤﻤﺎض اﻟﻼﻛﺘﻴﻜﻲ ﻫﺬه اﻟﻤﻀﺎﻋﻔﺎت ﻧﺎدرة‪ ،‬واﻟﻐﺎﻟﺒﻴﺔ اﻟﻌﻈﻤﻰ ﻣﻦ ﻫﺬه اﻟﺤﺎﻻت ﻣﺮﺗﺒﻄﺔ ﺑﺤﺎﻻت ﻣﺜﻞ ﺿﻌﻒ‬
‫اﻟﻜﺒﺪ أو وﻇﺎﺋﻒ اﻟﻜﻠﻰ‪ ،‬وﻟﻴﺲ ﺑﺎﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻧﻔﺴﻪ‪ [68].‬ﻟﻴﺲ ﻣﻦ اﻟﻤﺴﺘﺤﺴﻦ اﺳﺘﺨﺪام اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻓﻲ اﻷﺷﺨﺎص اﻟﺬﻳﻦ‬
‫]‪[69‬‬
‫ﻳﻌﺎﻧﻮن ﻣﻦ أﻣﺮاض اﻟﻜﻠﻰ اﻟﺤﺎدة‪ ،‬وﻟﻜﻦ ﻻ ﻳﺰال ﻳﺘﻢ اﺳﺘﺨﺪاﻣﻪ ﺑﺠﺮﻋﺎت أﻗﻞ ﻋﻨﺪ اﻟﻤﺼﺎﺑﻴﻦ ﺑﻤﺸﺎﻛﻞ ﻓﻲ اﻟﻜﻠﻰ‪.‬‬

‫اﻟﺠﻬﺎز اﻟﻬﻀﻤﻲ‬
‫ﻋ…‬
‫اﻧﺰﻋﺎﺟﺎ ﺷﺪﻳﺪً ا‪ .‬وﻫﻮ اﻷﻛﺜﺮ ﺷﻴﻮﻋً ﺎ ﻋﻨﺪ إﻋﻄﺎء اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻷول ﻣﺮة‪ ،‬أو ﻋﻨﺪ زﻳﺎدة‬
‫ً‬ ‫ﻳﻤﻜﻦ أن ﻳﺴﺒﺐ اﺿﻄﺮاب اﻟﺠﻬﺎز اﻟﻬﻀﻤﻲ‬
‫اﻟﺠﺮﻋﺔ‪ [64].‬ﻏﺎﻟ ًﺒﺎ ﻣﺎ ﻳﻤﻜﻦ ﺗﺠﻨﺐ اﻻﻧﺰﻋﺎج ﻋﻦ ﻃﺮﻳﻖ اﻟﺒﺪء ﺑﺠﺮﻋﺔ ﻣﻨﺨﻔﻀﺔ )‪ 1.0‬إﻟﻰ ‪ 1.7‬ﺟﺮام ‪ /‬ﻳﻮم( وزﻳﺎدة اﻟﺠﺮﻋﺔ‬
‫ﺗﺪرﻳﺠﻴﺎ‪ ،‬وﻟﻜﻦ ﺣﺘﻰ ﻣﻊ اﻟﺠﺮﻋﺎت اﻟﻤﻨﺨﻔﻀﺔ‪ ،‬ﻗﺪ ﻻ ﻳﺘﻤﻜﻦ ‪ ٪5‬ﻣﻦ اﻷﺷﺨﺎص ﻣﻦ ﺗﺤﻤﻞ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‪ [70][64].‬ﻗﺪ ﻳﺆدي‬
‫ً‬
‫]‪[24‬‬
‫اﺳﺘﺨﺪام ﻣﺴﺘﺤﻀﺮات ﺑﻄﻴﺌﺔ أو ﻣﻤﺘﺪة اﻟﻤﻔﻌﻮل إﻟﻰ زﻳﺎدة اﻟﻘﺪرة ﻋﻠﻰ اﻟﺘﺤﻤﻞ‪.‬‬

‫ارﺗﺒﻂ اﺳﺘﺨﺪام اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻋﻠﻰ اﻟﻤﺪى اﻟﻄﻮﻳﻞ ﺑﺰﻳﺎدة ﻣﺴﺘﻮﻳﺎت اﻟﻬﻮﻣﻮﺳﻴﺴﺘﻴﻦ‪ [71]،‬وﺳﻮء اﻣﺘﺼﺎص ﻓﻴﺘﺎﻣﻴﻦ‬
‫ﺑﻲ‪ [73][72][64].12‬ﺗﺮﺗﺒﻂ اﻟﺠﺮﻋﺎت اﻟﻌﺎﻟﻴﺔ واﻻﺳﺘﺨﺪام اﻟﻤﻄﻮل ﺑﺰﻳﺎدة ﺣﺪوث ﻧﻘﺺ ﻓﻴﺘﺎﻣﻴﻦ ﺑﻲ‪ [74]،12‬وﻳﻮﺻﻲ ﺑﻌﺾ‬
‫]‪[75‬‬
‫اﻟﺒﺎﺣﺜﻴﻦ ﺑﺎﺳﺘﺮاﺗﻴﺠﻴﺎت اﻟﻔﺤﺺ أو اﻟﻮﻗﺎﻳﺔ‪.‬‬

‫ﻋ…‬
‫اﻟﺤﻤﺎض اﻟﻼﻛﺘﻴﻜﻲ‬
‫ً‬
‫ﺗﻘﺮﻳﺒﺎ ﻻ ﻳﺤﺪث اﻟﺤﻤﺎض اﻟﻠﺒﻨﻲ أﺑﺪً ا ﻣﻊ اﺳﺘﺨﺪام اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ أﺛﻨﺎء اﻻﺳﺘﺨﺪام اﻟﺮوﺗﻴﻨﻲ ﻟﻪ‪ [76].‬ﺗﺒﻠﻎ ﻣﻌﺪﻻت اﻟﺤﻤﺎض اﻟﻠﺒﻨﻲ‬
‫)اﻟﻼﻛﺘﻴﻜﻲ( اﻟﻤﺮﺗﺒﻂ ﺑﺎﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﺣﻮاﻟﻲ ﺗﺴﻌﺔ ﻟﻜﻞ ‪ 100000‬ﺷﺨﺺ‪ /‬ﺳﻨﺔ‪ ،‬وﻫﻮ ﻣﺎ ﻳﻤﺎﺛﻞ اﻟﻤﻌﺪل اﻷﺳﺎﺳﻲ ﻟﻠﺤﻤﺎض اﻟﻠﺒﻨﻲ‬
‫ﻓﻲ ﻋﻤﻮم اﻟﺴﻜﺎن‪ [77].‬ﺣﻴﺚ ّﺑﻴﻨﺖ ﻣﺮاﺟﻌﺔ ﻣﻨﻬﺠﻴﺔ إﻟﻰ ﻋﺪم وﺟﻮد ﺑﻴﺎﻧﺎت ﺗﺮﺑﻂ ﺑﺸﻜﻞ ﻧﻬﺎﺋﻲ ﺑﻴﻦ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ واﻟﺤﻤﺎض‬
‫]‪[78‬‬
‫اﻟﻠﺒﻨﻲ‪.‬‬

‫ﻳﻌﺘﺒﺮ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ آﻣﻨًﺎ ﺑﺸﻜﻞ ﻋﺎم ﻟﻸﺷﺨﺎص اﻟﺬﻳﻦ ﻳﻌﺎﻧﻮن ﻣﻦ ﻣﺮض اﻟﻜﻠﻰ اﻟﻤﺰﻣﻦ اﻟﺨﻔﻴﻒ إﻟﻰ اﻟﻤﺘﻮﺳﻂ‪ ،‬ﻣﻊ ﺗﻘﻠﻴﻞ ﺗﻨﺎﺳﺒﻲ‬
‫ﻟﺠﺮﻋﺔ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ً‬
‫وﻓﻘﺎ ﻟﺸﺪة ﻣﻌﺪل اﻟﺘﺮﺷﻴﺢ اﻟﻜﺒﻴﺒﻲ اﻟﻤﻘﺪر )‪ (eGFR‬وﻣﻊ اﻟﺘﻘﻴﻴﻢ اﻟﺪوري ﻟﻮﻇﺎﺋﻒ اﻟﻜﻠﻰ )ﻋﻠﻰ ﺳﺒﻴﻞ‬
‫اﻟﻤﺜﺎل‪ ،‬اﻟﻘﻴﺎس اﻟﺪوري ﻟﻠﻜﺮﻳﺎﺗﻴﻨﻴﻦ ﻓﻲ اﻟﺒﻼزﻣﺎ(‪ [79].‬ﺗﻮﺻﻲ اﻟﻐﺬاء واﻟﺪواء اإدارةﻷﻣﺮﻳﻜﻴﺔ )‪ (FDA‬ﺑﺘﺠﻨﺐ اﺳﺘﺨﺪام‬
‫اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻓﻲ أﻣﺮاض اﻟﻜﻠﻰ اﻟﻤﺰﻣﻨﺔ اﻷﻛﺜﺮ ﺷﺪة‪ ،‬أﻗﻞ ﻣﻦ اﻟﺤﺪ اﻷﻗﺼﻰ ﻟﻤﻌﺪل اﻟﺘﺮﺷﻴﺢ اﻟﻜﺒﻴﺒﻲ اﻟﻤﻘﺪر )‪ eGFR) 30‬ﻣﻞ‪/‬‬
‫دﻗﻴﻘﺔ‪ 1.73 /‬ﻣﺘﺮ ﻣﺮﺑﻊ‪ [80].‬ﻳﻘﻞ اﻣﺘﺼﺎص اﻟﻜﺒﺪ ﻟﻼﻛﺘﺎت ﺑﺎﺳﺘﺨﺪام اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻷن اﻟﻼﻛﺘﺎت ﻫﻲ رﻛﻴﺰة ﻟﺘﻜﻮﻳﻦ اﻟﺴﻜﺮ ﻓﻲ‬
‫اﻟﻜﺒﺪ‪ ،‬وﻫﻲ ﻋﻤﻠﻴﺔ ﻳﺜﺒﻄﻬﺎ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‪ .‬ﻓﻲ اﻷﻓﺮاد اﻷﺻﺤﺎء ﻳﺘﻢ اﻟﺘﺨﻠﺺ ﻣﻦ ﻫﺬا اﻟﻔﺎﺋﺾ اﻟﻄﻔﻴﻒ ﻣﻦ ﺧﻼل آﻟﻴﺎت أﺧﺮى )ﺑﻤﺎ‬
‫ﻓﻲ ذﻟﻚ اﻻﻣﺘﺼﺎص ﻣﻦ ﻗﺒﻞ اﻟﻜﻠﻰ ﻏﻴﺮ اﻟﻤﺼﺎﺑﺔ(‪ ،‬وﻻ ﻳﺤﺪث ارﺗﻔﺎع ﻣﻠﺤﻮظ ﻓﻲ ﻣﺴﺘﻮﻳﺎت اﻟﻼﻛﺘﺎت ﻓﻲ اﻟﺪم‪ً [81].‬‬
‫ﻧﻈﺮا ﻟﻀﻌﻒ‬
‫ﺷﺪﻳﺪ ﻓﻲ وﻇﺎﺋﻒ اﻟﻜﻠﻰ‪ ،‬ﻳﺘﻢ ﺗﻘﻠﻴﻞ ﺗﺼﻔﻴﺔ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ واﻟﻼﻛﺘﺎت‪ ،‬ﻣﻤﺎ ﻳﺆدي إﻟﻰ زﻳﺎدة ﻣﺴﺘﻮﻳﺎت ﻛﻠﻴﻬﻤﺎ‪ ،‬ورﺑﻤﺎ ﻳﺘﺴﺒﺐ ﻓﻲ‬
‫ﺗﺮاﻛﻢ ﺣﻤﺾ اﻟﻼﻛﺘﻴﻚ‪ .‬ﻷن اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻳﻘﻠﻞ ﻣﻦ اﻣﺘﺼﺎص اﻟﻜﺒﺪ ﻟﻼﻛﺘﺎت‪ ،‬ﻓﺈن أي ﺣﺎﻟﺔ ﻗﺪ ﺗﻌﺠﻞ ﻣﻦ اﻟﺤﻤﺎض اﻟﻠﺒﻨﻲ ﻫﻲ‬
‫ﻣﻮاﻧﻊ‪ .‬ﺗﺸﻤﻞ اﻷﺳﺒﺎب اﻟﺸﺎﺋﻌﺔ إدﻣﺎن اﻟﻜﺤﻮل )ﺑﺴﺒﺐ اﺳﺘﻨﻔﺎد ﻣﺨﺎزن ‪ (+NAD‬وﻓﺸﻞ اﻟﻘﻠﺐ وأﻣﺮاض اﻟﺠﻬﺎز اﻟﺘﻨﻔﺴﻲ )ﺑﺴﺒﺐ‬
‫]‪[82‬‬
‫ﻋﺪم ﻛﻔﺎﻳﺔ أﻛﺴﺠﺔ اﻷﻧﺴﺠﺔ(؛ اﻟﺴﺒﺐ اﻷﻛﺜﺮ ﺷﻴﻮﻋً ﺎ ﻫﻮ ﻣﺮض اﻟﻜﻠﻰ‪.‬‬

‫ﻗﺪ ﻳﺤﺪث ً‬
‫أﻳﻀﺎ إﻧﺘﺎج اﻟﻼﻛﺘﺎت اﻟﻤﺮﺗﺒﻂ ﺑﺎﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻓﻲ اﻷﻣﻌﺎء اﻟﻐﻠﻴﻈﺔ‪ ،‬ﻣﻤﺎ ﻗﺪ ﻳﺴﺎﻫﻢ ﻓﻲ اﻹﺻﺎﺑﺔ ﺑﺎﻟﺤﻤﺎض اﻟﻠﺒﻨﻲ ﻟﺪى‬
‫اﻷﺷﺨﺎص اﻟﺬﻳﻦ ﻳﻌﺎﻧﻮن ﻣﻦ ﻋﻮاﻣﻞ اﻟﺨﻄﺮ‪ [83].‬وﻣﻊ ذﻟﻚ‪ ،‬ﻓﺈن اﻟﺪﻻﻟﺔ اﻟﺴﺮﻳﺮﻳﺔ ﻟﻬﺬا ﻏﻴﺮ ﻣﻌﺮوﻓﺔ‪ ،‬وﻳﻌﺰى ﺧﻄﺮ اﻹﺻﺎﺑﺔ‬
 ‫ﺑﺎﻟﺤﻤﺎض اﻟﻠﺒﻨﻲ اﻟﻤﺮﺗﺒﻂ ﺑﺎﻟﻤﻴﺘﻔﻮرﻣﻴﻦ إﻟﻰ اﻧﺨﻔﺎض اﻣﺘﺼﺎص اﻟﻜﺒﺪ ﺑﺪﻻً ﻣﻦ زﻳﺎدة إﻧﺘﺎج اﻷﻣﻌﺎء‪.‬‬
‫]‪[84][82][81‬‬

‫ﻳﺰداد ﺧﻄﺮ اﻹﺻﺎﺑﺔ ﺑﺎﻟﺤﻤﺎض اﻟﻠﺒﻨﻲ اﻟﻤﺮﺗﺒﻂ ﺑﺎﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ً‬

‫أﻳﻀﺎ ﺑﺴﺒﺐ ﺗﻨﺎول ﺟﺮﻋﺔ زاﺋﺪة ﻫﺎﺋﻠﺔ ﻣﻦ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‪ ،‬ﻋﻠﻰ اﻟﺮﻏﻢ‬
‫]‪[85‬‬
‫ﻣﻦ أن اﻟﺠﺮﻋﺎت اﻟﻜﺒﻴﺮة ﺟﺪً ا ﻻ ﺗﻜﻮن ﻗﺎﺗﻠﺔ ﻓﻲ ﻛﺜﻴﺮ ﻣﻦ اﻷﺣﻴﺎن‪.‬‬

‫ﺟﺮﻋﺔ ﻣﻔﺮﻃﺔ‬
‫ﻋ…‬
‫ﺗﺸﻤﻞ اﻷﻋﺮاض اﻷﻛﺜﺮ ﺷﻴﻮﻋً ﺎ ﺑﻌﺪ ﺗﻨﺎول ﺟﺮﻋﺔ زاﺋﺪة اﻟﻘﻲء‪ ،‬واﻹﺳﻬﺎل‪ ،‬وآﻻم اﻟﺒﻄﻦ‪ ،‬وﻋﺪم اﻧﺘﻈﺎم دﻗﺎت اﻟﻘﻠﺐ‪ ،‬واﻟﻨﻌﺎس‪،‬‬
‫داﻋﻤﺎ ﺑﺸﻜﻞ ﻋﺎم‪ ،‬ﺣﻴﺚ ﻻ‬
‫ً‬ ‫ً‬
‫ﻋﻼﺟﺎ‬ ‫وﻧﺎد ًرا ﻧﻘﺺ أو ارﺗﻔﺎع اﻟﺴﻜﺮ ﻓﻲ اﻟﺪم‪ [87][86].‬ﻳﻌﺘﺒﺮ ﻋﻼج اﻟﺠﺮﻋﺔ اﻟﺰاﺋﺪة ﻣﻦ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‬
‫]‪[88‬‬
‫ﻳﻮﺟﺪ ﻋﻼج ﻣﺤﺪد ﻣﻌﺮوف‪ .‬ﻳُ ﻨﺼﺢ ﺑﺎﻟﻌﻼﺟﺎت ﺧﺎرج اﻟﺠﺴﻢ ﻓﻲ اﻟﺠﺮﻋﺎت اﻟﺰاﺋﺪة اﻟﺸﺪﻳﺪة‪.‬‬

‫ﺑﺴﺒﺐ اﻟﻮزن اﻟﺠﺰﻳﺌﻲ اﻟﻤﻨﺨﻔﺾ ﻟﻠﻤﻴﺘﻔﻮرﻣﻴﻦ وﻧﻘﺺ اﻻرﺗﺒﺎط ﺑﺒﺮوﺗﻴﻦ اﻟﺒﻼزﻣﺎ‪ ،‬ﻓﺈن ﻫﺬه اﻟﺘﻘﻨﻴﺎت ﻟﻬﺎ ﻓﺎﺋﺪة ﻓﻲ إزاﻟﺔ‬
‫اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻣﻦ ﺑﻼزﻣﺎ اﻟﺪم‪ ،‬ﻣﻤﺎ ﻳﻤﻨﻊ زﻳﺎدة إﻧﺘﺎج اﻟﻼﻛﺘﺎت‪ [88].‬ﻳﻤﻜﻦ ﺗﺤﺪﻳﺪ ﻛﻤﻴﺔ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻓﻲ اﻟﺪم أو اﻟﺒﻼزﻣﺎ أو اﻟﻤﺼﻞ‬
‫ﻟﻤﺮاﻗﺒﺔ اﻟﻌﻼج أو ﺗﺄﻛﻴﺪ ﺗﺸﺨﻴﺺ اﻟﺘﺴﻤﻢ أو ﻟﻠﻤﺴﺎﻋﺪة ﻓﻲ ﺗﺤﻘﻴﻖ اﻟﻮﻓﺎة اﻟﺸﺮﻋﻲ‪ .‬ﻋﺎدة ﻣﺎ ﺗﻜﻮن ﺗﺮﻛﻴﺰات اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻓﻲ‬
‫اﻟﺪم أو اﻟﺒﻼزﻣﺎ ﻓﻲ ﻧﻄﺎق ‪ 4-1‬ﻣﻞ ﻏﻢ‪ /‬ﻟﺘﺮ ﻓﻲ اﻷﺷﺨﺎص اﻟﺬﻳﻦ ﻳﺘﻠﻘﻮن ﺟﺮﻋﺎت ﻋﻼﺟﻴﺔ‪ 120-40 ،‬ﻣﻞ ﻏﻢ‪ /‬ﻟﺘﺮ ﻓﻲ ﺿﺤﺎﻳﺎ‬
‫اﻟﺠﺮﻋﺔ اﻟﺰاﺋﺪة اﻟﺤﺎدة‪ ،‬و ‪ 200-80‬ﻣﻞ ﻏﻢ‪ /‬ﻟﺘﺮ ﻓﻲ اﻟﻮﻓﻴﺎت‪ .‬ﻳﺘﻢ اﺳﺘﺨﺪام ﺗﻘﻨﻴﺎت اﻟﻜﺮوﻣﺎﺗﻮﻏﺮاﻓﻴﺎ ﺑﺸﻜﻞ ﺷﺎﺋﻊ‪.‬‬

‫ﻋ…‬
‫اﻟﺘﻔﺎﻋﻼت‬

‫ﻳﺘﺴﺒﺐ اﻟﺴﻴﻤﻴﺘﻴﺪﻳﻦ ﻣﻀﺎد ﻣﺴﺘﻘﺒﻼت اﻟﻬﺴﺘﺎﻣﻴﻦ ‪ 2‬ﻓﻲ زﻳﺎدة ﺗﺮﻛﻴﺰ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻓﻲ اﻟﺒﻼزﻣﺎ ﻋﻦ ﻃﺮﻳﻖ ﺗﻘﻠﻴﻞ ﺗﺼﻔﻴﺔ‬
‫اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻋﻦ ﻃﺮﻳﻖ اﻟﻜﻠﻰ؛]‪ [89‬ﻳﺘﻢ اﻟﺘﺨﻠﺺ ﻣﻦ ﻛﻞ ﻣﻦ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ واﻟﺴﻴﻤﻴﺘﻴﺪﻳﻦ ﻣﻦ اﻟﺠﺴﻢ ﻋﻦ ﻃﺮﻳﻖ اﻹﻓﺮاز اﻷﻧﺒﻮﺑﻲ‬
‫)ﻧﻘﻞ اﻟﻤﻮاد ﻣﻦ اﻟﺸﻌﻴﺮات اﻟﺪﻣﻮﻳﺔ ﺣﻮل اﻷﻧﺒﻮب إﻟﻰ اﻟﺘﺠﻮﻳﻒ اﻷﻧﺒﻮﺑﻲ اﻟﻜﻠﻮي(‪ ،‬وﻛﻼﻫﻤﺎ وﺧﺎﺻﺔ اﻟﻜﺎﺗﻴﻮن )ﻣﻮﺟﺐ اﻟﺸﺤﻨﺔ(‬
‫ﻣﻦ اﻟﺴﻴﻤﻴﺘﻴﺪﻳﻦ‪ ،‬ﻗﺪ ﻳﺘﻨﺎﻓﺴﺎن ﻋﻠﻰ ﻧﻔﺲ آﻟﻴﺔ اﻟﻨﻘﻞ‪ [90].‬وﺟﺪت دراﺳﺔ ﻋﺸﻮاﺋﻴﺔ ﻣﺰدوﺟﺔ اﻟﺘﻌﻤﻴﺔ أن اﻟﻤﻀﺎد اﻟﺤﻴﻮي‬
‫ﺳﻴﻔﺎﻟﻴﻜﺴﻴﻦ ﻳﺰﻳﺪ ً‬
‫أﻳﻀﺎ ﻣﻦ ﺗﺮﻛﻴﺰات اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﺑﺂﻟﻴﺔ ﻣﻤﺎﺛﻠﺔ؛ ﻣﻦ اﻟﻨﺎﺣﻴﺔ اﻟﻨﻈﺮﻳﺔ ﻗﺪ ﺗﻨﺘﺞ اﻷدوﻳﺔ اﻟﻜﺎﺗﻴﻮﻧﻴﺔ اﻷﺧﺮى ﻧﻔﺲ‬
‫]‪[90‬‬
‫اﻟﺘﺄﺛﻴﺮ‪.‬‬

‫ﻧﻈﺮا ﻟﺘﺄﺛﻴﺮﻫﺎ ﻋﻠﻰ ﺣﺮﻛﺔ اﻟﻤﻌﺪة‪ .‬ﺗﻘﻠﻞ اﻷدوﻳﺔ اﻟﻤﻀﺎدة ﻟﻠﻜﻮﻟﻴﻦ ﻣﻦ‬ ‫ﻳﺘﻔﺎﻋﻞ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ً‬
‫أﻳﻀﺎ ﻣﻊ اﻷدوﻳﺔ اﻟﻤﻀﺎدة ﻟﻠﻜﻮﻟﻴﻦ‪ً ،‬‬
‫ﺣﺮﻛﺔ اﻟﻤﻌﺪة‪ ،‬وﺗﻄﻴﻞ ﻣﻦ اﻟﻮﻗﺖ اﻟﺬي ﺗﻘﻀﻴﻪ اﻷدوﻳﺔ ﻓﻲ اﻟﺠﻬﺎز اﻟﻬﻀﻤﻲ‪ .‬ﻗﺪ ﻳﺆدي ﻫﺬا اﻟﻀﻌﻒ إﻟﻰ اﻣﺘﺼﺎص اﻟﻤﺰﻳﺪ ﻣﻦ‬
‫اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ أﻛﺜﺮ ﻣﻦ ﻋﺪم وﺟﻮد ﻋﻘﺎر ﻣﻀﺎد ﻟﻠﻜﻮﻟﻴﻦ‪ ،‬ﻣﻤﺎ ﻳﺰﻳﺪ ﻣﻦ ﺗﺮﻛﻴﺰ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻓﻲ اﻟﺒﻼزﻣﺎ وﻳﺰﻳﺪ ﻣﻦ ﻣﺨﺎﻃﺮ اﻵﺛﺎر‬
‫]‪[91‬‬
‫اﻟﻀﺎرة‪.‬‬

‫آﻟﻴﺔ اﻟﺘﺄﺛﻴﺮ‬

‫اﻗﺘُ ِﺮﺣﺖ اﻟﻌﺪﻳﺪ ﻣﻦ اﻵﻟﻴﺎت اﻟﻤﺤﺘﻤﻠﺔ ﻟﻌﻤﻞ اﻟﻤﻴﺘﻔﻮرﻣﻦ وﻟﻜﻦ ﺑﻘﻴﺖ اﻵﻟﻴﺔ اﻟﺠﺰﻳﺌﻴﺔ ﻟﻠﻤﻴﺘﻔﻮرﻣﻴﻦ ﻏﻴﺮ ﻣﻔﻬﻮﻣﺔ ً‬
‫ﺗﻤﺎﻣﺎ‪ .‬ﻓﻤﻦ‬
‫اﻟﻤﻨﺸﻂ ﺑﺎﻷدﻳﻨﻮﺳﻴﻦ‬
‫اﻻﻟﻴﺎت اﻟﻤﻘﺘﺮﺣﺔ أﻧﻪ ﻳﻌﻤﻞ ﻋﻠﻰ ﺗﺜﺒﻴﻂ اﻟﺴﻠﺴﻠﺔ اﻟﺘﻨﻔﺴﻴﺔ ﻟﻠﻤﻴﺘﻮﻛﻮﻧﺪرﻳﺎ )اﻟﻤﻌﻘﺪ ‪ ،(1‬ﺗﻨﺸﻴﻂ ﺑﺮوﺗﻴﻦ ﻛﻴﻨﻴﺰ ُ‬
‫ّﺎﺟﻢ ﻋﻦاﻟﺠﻠﻮﻛﺎﺟﻮن ﻣﻊ اﻧﺨﻔﺎض ﺗﻨﺸﻴﻂ‬
‫اﻟﺤﻠﻘﻲ )‪ (cAMP‬اﻟﻨ ِ‬
‫أﺣﺎدي اﻟﻔﻮﺳﻔﺎت‪ ،‬ﺗﺜﺒﻴﻂ ارﺗﻔﺎع اﺣﺎدي ﻓﻮﺳﻔﺎت اﻷدﻳﻨﻮزﻳﻦ َ‬
‫ﺑﺮوﺗﻴﻦ ﻛﻴﻨﻴﺰ أﻟﻔﺎ )‪ ، (PKA‬ﺗﺜﺒﻴﻂ ﻧﺎزع اﻟﻬﻴﺪروﺟﻴﻦ ﻣﻦ ﻓﻮﺳﻔﺎت اﻟﺠﻠﻴﺴﺮول ﻓﻲ اﻟﻤﺎﻳﺘﻮﻛﻨﺪرﻳﺎ‪ ،‬وﺗﺄﺛﻴﺮه ﻋﻠﻰ اﻟﻨّﺒﻴﺘﺎت‬
 ‫اﻟﺸﻬﻴﺔ ﻳُ ﺆدي إﻟﻰ ﻓﻘﺪاﻧﻬﺎ ﻋﻨﺪ ﻣﻌﻈﻢ اﻟﻨﺎس‪ ،‬ﻣﻤﺎ ﻳﻘﻠﻞ ﻣﻦ‬ ‫ٌ‬
‫ﺗﺄﺛﻴﺮات ﻋﻠﻰ ّ‬ ‫اﻟﺠﺮﺛﻮﻣﻴﺔ اﻟﻤﻌﻮﻳّ ﺔ‪ [94][93][92].‬ﻛﻤﺎ أنّ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻟﻪ‬
‫اﻟﺴﻌﺮات اﻟﺤﺮارﻳّ ﺔ‪ [95].‬وﻳﻘﻠﻞ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻣﻦ اﺳﺘﺤﺪاث اﻟﺴﻜﺮ )إﻧﺘﺎج اﻟﺠﻠﻮﻛﻮز( ﻓﻲ اﻟﻜﺒﺪ‪[96] [83].‬ﻛﻤﺎ ﻳﺜﺒﻂ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‬
‫ّ‬
‫اﻟﻘﺎﻋﺪي ﻣﻦ اﻟﻐﺪة اﻟﻨّﺨﺎﻣﻴﺔ ﻟﻬﺮﻣﻮن اﻟﻨّﻤﻮ‪ ،‬وﻫﺮﻣﻮن ﻗﺸﺮ اﻟﻜﻈﺮ‪ ،‬واﻟﻬﺮﻣﻮن اﻟﻤﻨﺒﻪ ﻟﻠﺠﺮﻳﺐ‪ ،‬واﻟﺘﻌﺒﻴﺮ اﻟﻮراﺛﻲ ﻋﻦ‬
‫ّ‬ ‫اﻹﻓﺮاز‬
‫اﻟﺒﺮوﺑﻴﻮﻣﻴﻼﻧﻮﻛﻮرﺗﻴﻦ ]‪-[97‬ﺑﺮوﺗﻴﻦ ﺳﻜﺮي ﻣﺆﻟﻒ ﻣﻦ ‪ 240‬ﺣﻤﺾ أﻣﻴﻨﻲ‪ -‬اﻟﺬي ﻳُ ﺴﺎﻫﻢ ﻓﻲ ﺗﺤﺴﻴﻦ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻟﺤﺴﺎﺳﻴﺔ‬
‫اﻷﻧﺴﻮﻟﻴﻦ ﻓﻲ اﻟﺠﺴﻢ ﻣﻊ ﻋﺪّ ة ﻃﺮق ﻋﻤﻞ ﻟﻪ ﻋﻠﻰ اﻷﻧﺴﺠﺔ اﻟﺘﻲ ﺗﺸﻤﻞ اﻟﻜﺒﺪ واﻟﻌﻀﻼت اﻟﻬﻴﻜﻠﻴﺔ واﻷﻧﺴﺠﺔ اﻟﺪﻫﻨﻴﺔ‬
‫واﻟﻤﺒﺎﻳﺾ‪ [98][50].‬اﻟﻤﺮﻳﺾ اﻟﻌﺎدي اﻟﻤﺼﺎب باﻟﺴﻜﺮي ﻣﻦ اﻟﻨﻮع اﻟﺜﺎﻧﻲ ﻟﺪﻳﻪ ﺛﻼﺛﺔ أﺿﻌﺎف اﻟﻤﻌﺪل اﻟﻄﺒﻴﻌﻲ ﻻﺳﺘﺤﺪاث اﻟﺴﻜﺮ‬
‫اﻟﺜﻠﺚ‪[99].‬‬ ‫وﻟﻜﻦ اﻟﻌﻼج ﺑﺎﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻳﻘﻠﻞ ﻫﺬا ﻷﻛﺜﺮ ﻣﻦ‬

‫اﻟﻤﻨﺸﻂ ﺑﺎﻷدﻳﻨﻮﺳﻴﻦ أﺣﺎدي اﻟﻔﻮﺳﻔﺎت )‪ (AMPK‬ﻟﻴﻘﻮم ﺑﺘﺜﺒﻴﻂ إﻧﺘﺎج اﻟﺠﻠﻮﻛﻮز‬

‫ﻳﺤﺘﺎج اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ إﻟﻰ ﺗﻨﺸﻴﻂ ﺑﺮوﺗﻴﻦ ﻛﻴﻨﻴﺰ ُ‬
‫ﻣﻬﻤﺎ ﻓﻲ إﺷﺎرات اﻷﻧﺴﻮﻟﻴﻦ‪ ،‬وﺗﻮازن ﻃﺎﻗﺔ اﻟﺠﺴﻢ‬ ‫ﻓﻲ اﻟﻜﺒﺪ‪ [100].‬و ﺑﺮوﺗﻴﻦ ﻛﻴﻨﻴﺰ ُ‬
‫اﻟﻤﻨﺸﻂ ﺑﺎﻷدﻳﻨﻮﺳﻴﻦ ﻫﻮ إﻧﺰﻳﻢ ﻳﻠﻌﺐ دو ًرا ً‬
‫ﺑﺎﻟﻜﺎﻣﻞ‪ ،‬واﺳﺘﻘﻼب اﻟﺠﻠﻮﻛﻮز واﻟﺪﻫﻮن‪ [101].‬وﺣﻴﺚ ان ﺗﻨﺸﻴﻂ اﻷدﻳﻨﻮﺳﻴﻦ أﺣﺎدي اﻟﻔﻮﺳﻔﺎت ﻛﺎن ﻣﻄﻠﻮﺑًﺎ ﻟﺰﻳﺎدة اﻟﺘّ ﻌﺒﻴﺮﻋﻦ‬
‫ﺷﺮﻳﻚ ﻣﺜﻨﻮي ﻣﻐﺎﻳﺮ‪ ،‬واﻟﺬي ﺑﺪوره أدّ ى إﻟﻰ ﺗﺜﺒﻴﻂ اﻟﺘّ ﻌﺒﻴﺮ ﻋﻦ اﻟﺠﻴﻨﺎت اﻟﻜﺒﺪﻳﺔ ﻟﺘﻜﻮﻳﻦ اﻟﺠﻠﻮﻛﻮز أﻻ وﻫﻲ ﻛﻞ ﻣﻦ اﻟﻔﺴﻔﻮﻳﻨﻮل‬
‫ﻛﺜﻴﺮا ﻣﺎ ﻳﺴﺘﺨﺪم اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻓﻲ اﻷﺑﺤﺎث ﺟﻨ ًﺒﺎ إﻟﻰ ﺟﻨﺐ ﻣﻊ‬ ‫ﺑﻴﺮوﻓﺎت ﻛﺎرﺑﻮﻛﺴﻴﻜﻴﻨﺎز واﻟﺠﻠﻮﻛﻮز ‪-6‬ﻓﻮﺳﻔﺎﺗﺎز‪[102].‬‬
‫ً‬
‫رﻳﺒﻮﻧﻮﻛﻠﻴﻮﺗﻴﺪ ‪ AICA‬ﻛﻤﺤﻔﺰ ﻟﻸدﻳﻨﻮﺳﻴﻦ أﺣﺎدي اﻟﻔﻮﺳﻔﺎت‪ .‬ﻻ ﺗﺰال اﻵﻟﻴﺔ اﻟﺘﻲ ﻣﻦ ﺧﻼﻟﻬﺎ ﻳﺰﻳﺪ اﻟﺒﺎﻳﺠﻮاﻧﻴﺪات ﻣﻦ ﻧﺸﺎط‬
‫اﻷدﻳﻨﻮﺳﻴﻦ أﺣﺎدي اﻟﻔﻮﺳﻔﺎت ﻏﻴﺮ ﻣﺆﻛﺪة‪ .‬وﻣﻊ ذﻟﻚ‪ ،‬ﻳﺰﻳﺪ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻣﻦ ﺗﺮﻛﻴﺰ اﻷدﻳﻨﻮزﻳﻦ أﺣﺎدي اﻟﻔﻮﺳﻔﺎت )‪) (AMP‬ﻋﻠﻰ‬
‫ﻋﻜﺲ اﻟﺘﻐﻴﻴﺮ ﻓﻲ إﺟﻤﺎﻟﻲ ‪ AMP‬أو إﺟﻤﺎﻟﻲ ‪ /AMP‬ﺛﻼﺛﻲ ﻓﻮﺳﻔﺎت اﻷدﻳﻨﻮزﻳﻦ(‪[103] .‬ﻳﺜﺒﻂ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ إﻧﺘﺎج اﻷدﻳﻨﻮزﻳﻦ‬
‫أﺣﺎدي اﻟﻔﻮﺳﻔﺎت اﻟﺪوري‪ ،‬ﻣﻤﺎ ﻳﻌﻴﻖ ﻋﻤﻞ اﻟﺠﻠﻮﻛﺎﺟﻮن‪ ،‬وﺑﺎﻟﺘﺎﻟﻲ ﻳﻘﻠﻞ ﻣﺴﺘﻮﻳﺎت اﻟﺠﻠﻮﻛﻮز أﺛﻨﺎء اﻟﺼﻴﺎم‪ [104].‬ﻳﺆدي‬
‫أﻳﻀﺎ إﻟﻰ ﺣﺪوث ﺗﺤﻮل ﻋﻤﻴﻖ ﻓﻲ ﻣﻠﻒ اﻟﻤﺠﺘﻤﻊ اﻟﻤﻴﻜﺮوﺑﻲ اﻟﺒﺮازي ﻓﻲ اﻟﻔﺌﺮان اﻟﻤﺼﺎﺑﺔ ﺑﺪاء اﻟﺴﻜﺮي‪ ،‬وﻗﺪ ﻳﺴﺎﻫﻢ‬‫اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ً‬
‫اﻟﺠﻠﻮﻛﺎﺟﻮن‪[93].‬‬ ‫ذﻟﻚ ﻓﻲ ﻃﺮﻳﻘﺔ ﻋﻤﻠﻪ رﺑﻤﺎ ﻣﻦ ﺧﻼل اﻟﺘﺄﺛﻴﺮ ﻋﻠﻰ إﻓﺮاز اﻟﺒﺒﺘﻴﺪ ‪ 1-‬اﻟﺬي ﻳﺸﺒﻪ‬

‫ﺣﺴﺎﺳﻴﺔ اﻷﻧﺴﻮﻟﻴﻦ‪ ،‬ﻛﻤﺎ وﻳﻌﺰز ﻣﻦ اﻣﺘﺼﺎص‬

‫ّ‬ ‫ﺑﺎﻹﺿﺎﻓﺔ إﻟﻰ ﺗﺜﺒﻴﻂ إﻧﺘﺎج اﻟﺠﻠﻮﻛﻮز ﻓﻲ اﻟﻜﺒﺪ ﻓﺎن اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻳﺰﻳﺪ ﻣﻦ‬
‫اﻟﺠﻠﻮﻛﻮز اﻟﻄﺮﻓﻲ )ﻋﻦ ﻃﺮﻳﻖ ﺗﺤﻔﻴﺰ اﻟﻔﺴﻔﺮة ﻟﻌﺎﻣﻞ ﻣﻌﺰز ‪ ،(GLUT4‬ﻛﻤﺎ وﻳﻘﻠﻞ ﻣﻦ ﺗﺜﺒﻴﻂ أﻛﺴﺪة اﻷﺣﻤﺎض اﻟﺪﻫﻨﻴﺔ ﺑﻔﻌﻞ‬
‫اﻷﻧﺴﻮﻟﻴﻦ]‪ [105‬وﻳﻘﻠﻞ اﻣﺘﺼﺎص اﻟﺠﻠﻮﻛﻮز ﻣﻦ اﻟﻘﻨﺎة اﻟﻬﻀﻤﻴﺔ‪ .‬ﻳُ ﻌﺘﻘﺪ ان زﻳﺎدة اﻻﺳﺘﺨﺪام اﻟﻄﺮﻓﻲ ﻟﻠﺠﻠﻮﻛﻮز ﻧﺎﺗﺠﺔ ﻋﻦ ﺗﺤﺴﻦ‬
‫ارﺗﺒﺎط اﻷﻧﺴﻮﻟﻴﻦ ﺑﻤﺴﺘﻘﺒﻼت اﻷﻧﺴﻮﻟﻴﻦ‪[106]،‬ﺣﻴﺚ أﺛﺒﺖ زﻳﺎدة ارﺗﺒﺎط اﻷﻧﺴﻮﻟﻴﻦ ﺑﻤﺴﺘﻘﺒﻼﺗﻪ ﺑﻌﺪ اﻟﻌﻼج ﺑﺎﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻟﺪى‬
‫اﻟﺜﺎﻧﻲ‪[107].‬‬ ‫ﻣﺮﺿﻰ اﻟﺴﻜﺮي ﻣﻦ اﻟﻨﻮع‬

‫ﻣﻦ اﻟﻤﺤﺘﻤﻞ ً‬
‫أﻳﻀﺎ أن اﻷدﻳﻨﻮﺳﻴﻦ أﺣﺎدي اﻟﻔﻮﺳﻔﺎت ﻳﻠﻌﺐ دو ًرا ﻓﻲ زﻳﺎدة ﺣﺴﺎﺳﻴﺔ اﻷﻧﺴﻮﻟﻴﻦ اﻟﻄﺮﻓﻴﺔ‪ ،‬ﺣﻴﺚ ﻳﺆدي ﺗﻨﺎول‬
‫اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ إﻟﻰ زﻳﺎدة ﻧﺸﺎط اﻷدﻳﻨﻮﺳﻴﻦ أﺣﺎدي اﻟﻔﻮﺳﻔﺎت ﻓﻲ اﻟﻌﻀﻼت اﻟﻬﻴﻜﻠﻴﺔ‪ [108]،‬وﻣﻦ اﻟﻤﻌﺮوف أن اﻷدﻳﻨﻮﺳﻴﻦ أﺣﺎدي‬
‫اﻟﻔﻮﺳﻔﺎت ﻳﺘﺴﺒﺐ ﻓﻲ ﻧﺸﺮ ﻋﺎﻣﻞ ‪ GLUT4‬ﻓﻲ ﻏﺸﺎء اﻟﺒﻼزﻣﺎ‪ ،‬ﻣﻤﺎ ﻳﺆدي إﻟﻰ اﻣﺘﺼﺎص اﻟﺠﻠﻮﻛﻮز اﻟﻤﺴﺘﻘﻞ ﻋﻦ اﻷﻧﺴﻮﻟﻴﻦ‪ .‬ﻛﻤﺎ‬
‫أن ﺑﻌﺾ اﻟﻌﻤﻠﻴﺎت اﻷﻳﻀﻴﺔ ﻟﻠﻤﻴﺘﻔﻮرﻣﻴﻦ ﺗﺤﺪث ﺑﻮاﺳﻄﺔ آﻟﻴﺎت ﻣﺴﺘﻘﻠﺔ ﻋﻦ اﻷدﻳﻨﻮﺳﻴﻦ أﺣﺎدي اﻟﻔﻮﺳﻔﺎت‪.‬‬

‫ﻟﻠﻤﻴﺘﻔﻮرﻣﻴﻦ ﺗﺄﺛﻴﺮات ﻏﻴﺮ ﻣﺒﺎﺷﺮة ﻣﻀﺎدة ﻟﻸﻟﻨﺪروﺟﻴﻦ ﻟﺪى اﻟﻨﺴﺎء اﻟﻠﻮاﺗﻲ ﻳﻌﺎﻧﻴﻦ ﻣﻦ ﻣﻘﺎوﻣﺔ اﻷﻧﺴﻮﻟﻴﻦ ﻣﺜﻞ ﺗﻠﻚ اﻟﻤﺼﺎﺑﺎت‬
‫ﺑﻤﺘﻼزﻣﺔ ﺗﻜﻴﺲ اﻟﻤﺒﺎﻳﺾ وذﻟﻚ ﺑﺴﺒﺐ آﺛﺎره اﻟﻤﻔﻴﺪة ﻋﻠﻰ ﺣﺴﺎﺳﻴﺔ اﻷﻧﺴﻮﻟﻴﻦ‪ [109],‬ﺣﻴﺖ اﻧﻪ ﻗﺪ ﻳﺴﺎﻫﻢ ﻓﻲ ﺗﻘﻴﻞ ﻣﺴﺘﻮﻳﺎت‬
‫ﻫﺮﻣﻮن اﻟﺘﺴﺘﻮﺳﺘﻴﺮون ﻟﺪى ﻫﺆﻻء اﻟﻨﺴﺎء ﺑﻨﺴﺒﺔ ﺗﺼﻞ إﻟﻰ ‪[109] .٪50‬وﻟﻜﻦ ﻋﻠﻰ اﻟﺮﻏﻢ ﻣﻦ ذﻟﻚ‪ ,‬ﻓﻘﺪ ﺟﺪت ﻣﺮاﺟﻌﺔ ﻛﻮﻛﺮﻳﻦ أن‬
‫اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻛﺎن ﻓﻌّ ًﺎﻻ ﺑﺸﻜﻞ ﻃﻔﻴﻒ ﻓﻘﻂ ﻟﺨﻔﺾ ﻣﺴﺘﻮﻳﺎت اﻷﻧﺪروﺟﻴﻦ ﻟﺪى اﻟﻨﺴﺎء اﻟﻤﺼﺎﺑﺎت بﻣﺘﻼزﻣﺔ ﺗﻜﻴﺲ‬
‫اﻟﻤﺒﺎﻳﺾ‪[110].‬‬
 ‫ﻛﻤﺎ أن ﻟﻠﻤﻴﺘﻔﻮرﻣﻴﻦ ﺗﺄﺛﻴﺮات ﻣﻬﻤﺔ ﻋﻠﻰ ﻣﻴﻜﺮوﺑﻴﻮم اﻷﻣﻌﺎء‪ ،‬ﻣﺜﻞ ﺗﺄﺛﻴﺮه ﻋﻠﻰ زﻳﺎدة إﻧﺘﺎج اﻷﻏﻤﺎﺗﻴﻦ ﺑﻮاﺳﻄﺔ ﺑﻜﺘﻴﺮﻳﺎ اﻷﻣﻌﺎء‪،‬‬
‫ﻣﺆﻛﺪة‪[113][112][111].‬‬ ‫ﻟﻜﻦ ﺗﺒﻘﻰ اﻷﻫﻤﻴﺔ اﻟﻨﺴﺒﻴﺔ ﻟﻬﺬه اﻵﻟﻴﺔ ﻣﻘﺎرﻧﺔ ﺑﺎﻵﻟﻴﺎت اﻷﺧﺮى ﻏﻴﺮ‬

‫ﺣﺮاﺋﻚ اﻟﺪواء‬

‫اﻣﺘﺼﺎﺻﻪ ﻳﻜﻮن‬
‫َ‬ ‫ً‬
‫ﺑﻴﻮﻟﻮﺟﻴﺎ ﺑﻨﺴﺒﺔ ‪ ٪60-50‬إذا ا ِﺧﺬ ﻋﻦ ﻃﺮﻳﻖ اﻟﻔﻢ ﻓﻲ ﻇﻞ ﻇﺮوف اﻟﺼﻴﺎم‪ ،‬ﻛﻤﺎ أنّ‬ ‫ﺗﻮاﻓﺮا‬
‫ً‬ ‫ﻳﻤﺘﻠﻚ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‬
‫ﺑَﻄﻴﺌﺎ‪[114] [90],‬ﻛﻤﺎ وﻳﺼﻞ إﻟﻰ ذروة ﺗﺮﻛﻴﺰه ﻓﻲ اﻟﺒﻼزﻣﺎ )‪ (Cmax‬ﻓﻲ ﻏﻀﻮن ‪ 3-1‬ﺳﺎﻋﺎت ﻣﻦ ﺗﻨﺎول اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ اﻟﻔﻮري‬
‫اﻟﻤﻔﻌﻮل و‪ 8-4‬ﺳﺎﻋﺎت ﻣﻊ ﺗﺮﻛﻴﺒﺎت ﻣﻤﺘﺪة اﻹﻃﻼق‪[114] [90].‬ﻛﻤﺎ ان ارﺗﺒﺎط اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﺑﺒﺮوﺗﻴﻨﺎت اﻟﺒﻼزﻣﺎ ﻻ ﻳﻜﺎد ﻳﺬﻛﺮ‪ ،‬ﻛﻤﺎ‬
‫ﻳﺘﻀﺢ ﻣﻦ ﺣﺠﻢ ﺗﻮزﻳﻌﻪ اﻟﻮاﺿﺢ ﻟﻠﻐﺎﻳﺔ )‪ 1000-300‬ﻟﺘﺮ ﺑﻌﺪ ﺟﺮﻋﺔ واﺣﺪة(‪ .‬ﻋﺎدة ﻣﺎ ﻳﺘﻢ اﻟﻮﺻﻮل إﻟﻰ ﺣﺎﻟﺔ اﻟﺜﺒﺎت ﻓﻲ ﻏﻀﻮن‬
‫]‪[90‬‬
‫ﻳﻮم إﻟﻰ ﻳﻮﻣﻴﻦ‪.‬‬

‫ﻛﻤﺎ أن ﻟﻠﻤﻴﺘﻔﻮرﻣﻴﻦ ﻗﻴﻢ ﺛﺎﺑﺘﺔ ﻟﺘﻔﻜﻚ اﻟﺤﻤﺾ اﻟﻠﻮﻏﺎرﻳﺘﻤﻲ )‪ (pKa‬ﺗﺒﻠﻎ وﻗﻴﻤﻬﺎ ‪ 2.8‬و ‪ ،11‬ﻟﺬﻟﻚ ﻓﻬﻮ ﻣﻮﺟﻮد ﻓﻲ ﻧﻄﺎق واﺳﻊ‬
‫ﻛﺎﻷﻧﻮاع اﻟﻜﺎﺗﻴﻮﻧﻴﺔ اﻟﻤﺤﺒﺔ ﻟﻠﻤﺎء ﻋﻨﺪ ﻗﻴﻢ اﻟﺮﻗﻢ اﻟﻬﻴﺪروﺟﻴﻨﻲ اﻟﻔﺴﻴﻮﻟﻮﺟﻴﺔ‪ .‬ﻛﻤﺎ ان ﻗﻴﻢ ﺛﺎﺑﺖ ﺗﻔﻜﻚ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ اﻟﻠﻮﻏﺎرﻳﺘﻤﻴﺔ‬
‫ﺟﻌﻠﺘﻪ ﻗﺎﻋﺪة ﻗﻮﻳﺔ وأﻗﻮى ﻣﻦ ﻣﻌﻈﻢ اﻷدوﻳﺔ اﻟﻘﺎﻋﺪﻳﺔ اﻷﺧﺮى ﻣﻊ أﻗﻞ ﻣﻦ ‪ ٪0.01‬ﻏﻴﺮ ﻣﺆﻳﻦ ﻓﻲ اﻟﺪم‪ .‬ﻋﻼوة ﻋﻠﻰ ذﻟﻚ‪ ،‬ﻓﺈن‬
‫ﻗﺎﺑﻠﻴﺔ اﻟﺬوﺑﺎن ﻓﻲ اﻟﺪﻫﻮن ﻟﻸﻧﻮاع ﻏﻴﺮ اﻟﻤﺄﻳﻨﺔ ﺗﻜﻮن ﻃﻔﻴﻔﺔ ﻛﻤﺎ ﻳﺘﻀﺢ ﻣﻦ اﻧﺨﻔﺎض ﻗﻴﻤﺔ اﻟﻠﻮﻏﺎرﻳﺘﻢ ﻟﻤﻌﺎﻣﻞ اﻟﺘﻮزﻳﻊ ﻟﻠﺸﻜﻞ‬
‫ﻏﻴﺮ اﻟﻤﺆﻳﻦ ﺑﻴﻦ اﻷوﻛﺘﺎﻧﻮل واﻟﻤﺎء اﻟﺘﻲ ﺗﺒﻠﻎ ﻗﻴﻤﺘﻬﺎ ‪ .1.43‬ان ﻫﺬه اﻟﻤﻌﻠﻤﺎت اﻟﻜﻴﻤﻴﺎﺋﻴﺔ ﺗﺸﻴﺮ إﻟﻰ اﻧﺨﻔﺎض ﺷﺤﻮم اﻟﺪﻫﻮن‬
‫واﻟﺬي ﺑﺪوره ﻳﺠﻌﻞ ﻣﻦ اﻻﻧﺘﺸﺎر اﻟﺴﻠﺒﻲ اﻟﺒﺴﻴﻂ اﻟﺴﺮﻳﻊ ﻟﻠﻤﻴﺘﻔﻮرﻣﻴﻦ ﻋﺒﺮ أﻏﺸﻴﺔ اﻟﺨﻼﻳﺎ أﻣﺮ ﻏﻴﺮ ﻣﺤﺘﻤﻞ‪ ،‬وﻛﻨﺘﻴﺠﺔ ﻻﻧﺨﻔﺎض‬
‫ﻗﺎﺑﻠﻴﺘﻪ ﻟﻠﺬوﺑﺎن ﻓﻲ اﻟﺪّ ﻫﻮن ﻓﺈﻧﻪ ﻳﺘﻄﻠﺐ اﻟﻨّﺎﻗﻞ ‪ SLC22A1‬ﻣﻦ أﺟﻞ دﺧﻮل اﻟﺨﻼﻳﺎ‪[116] [115].‬ﻳﻜﻮن اﻟﻠﻮﻏﺎرﻳﺘﻢ ﻟﻤﻌﺎﻣﻞ‬
‫اﻟﺘﻮزﻳﻊ )‪ (logP‬ﻟﻠﻤﻴﺘﻔﻮرﻣﻴﻦ أﻗﻞ ﻣﻦ ﻣﺜﻴﻠﻪ ﻓﻲ اﻟﻔﻴﻨﻔﻮرﻣﻴﻦ )‪ (0.84−‬وذﻟﻚ ﻷن ﺑﺪاﺋﻠﻴﻦ ﻣﻦ اﻟﻤﻴﺜﻴﻞ ﻋﻠﻰ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‬
‫ﺣﺎﻟﻴﺎ ﻫﻨﺎﻟﻚ اﻟﻤﺰﻳﺪ ﻣﻦ‬
‫ً‬ ‫ﻳﻀﻔﻴﺎن ﻗﺪ ًرا أﻗﻞ ﻣﻦ اﻟﻤﺤﺒﺔ ﻟﻠﺪﻫﻮن ﻣﻦ اﻟﺴﻠﺴﻠﺔ اﻟﺠﺎﻧﺒﻴﺔ اﻷﻛﺒﺮ ﻟﻠﻔﻴﻨﻴﻠﺜﻴﻞ ﻓﻲ اﻟﻔﻴﻨﻔﻮرﻣﻴﻦ‪.‬‬
‫اﻟﻤﺸﺘﻘﺎت اﻟﻤﺤﺒﺔ ﻟﻠﺪﻫﻮن ﻣﻦ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻗﻴﺪ اﻟﺪّ راﺳﺔ ﺑﻬﺪف إﻧﺘﺎج ﻋﻘﺎﻗﻴﺮ أوﻟﻴﺔ ذات اﻣﺘﺼﺎص ﻓﻤﻮي أﻓﻀﻞ ﻣﻦ‬
‫]‪[117‬‬
‫اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‪.‬‬

‫ﻻ ﻳَ ﺴﺘﻘﻠﺐ )إﺟﺮاء اﻟﻌﻤﻠﻴﺎت اﻻﻳﻀﻴﻰ ة ﻋﻠﻴﻪ( اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ وا ّﻧﻤﺎ ﻳﺨﺮج ﻣﻦ اﻟﺠﺴﻢ ﻋﻦ ﻃﺮﻳﻖ اﻹﻓﺮاز أﻧﺒﻮﺑﻲ وﻳﺨﺮج دون‬
‫ﺗﻐﻴﻴﺮ ﻓﻲ اﻟﺒﻮل‪ .‬ﻛﻤﺎ ا ّﻧﻪ ﻻ ﻳﻤﻜﻦ اﻛﺘﺸﺎﻓﻪ ﻓﻲ ﺑﻼزﻣﺎ اﻟﺪم ﺧﻼل ‪ 24‬ﺳﺎﻋﺔ إذا اﻋﻄﻲ ﺟﺮﻋﺔ ﻓﻤﻮﻳﺔ واﺣﺪة‪ .‬ﻣﺘﻮﺳﻂ ﻋﻤﺮ اﻟﻨّﺼﻒ‬
‫ّ‬
‫ﻟﻠﺘﺨﻠﺺ ﻣﻦ اﻟﺒﻼزﻣﺎ ﻫﻮ ‪ 6.2‬ﺳﺎﻋﺔ‪[90].‬ﻛﻤﺎ و ﻳﻮزﻳﻊ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ وﻳﺒﺪو أﻧﻪ ﻳﺘﺮاﻛﻢ ﻓﻲ ﺧﻼﻳﺎ اﻟﺪم اﻟﺤﻤﺮاء ﻣﻊ ﻋﻤﺮ ﻧﺼﻔﻲ‬
‫أﻃﻮل ﺑﻜﺜﻴﺮ ﻟﻠﺘﺨﻠﺺ وﺗﺒﻠﻎ ‪ 17.6‬ﺳﺎﻋﺔ]‪) [90‬وﻗﺪ اﺑﻠﻎ ﻋﻦ أﻧﻪ ﻳﺘﺮاوح ﻣﻦ ‪ 18.5‬إﻟﻰ ‪ 31.5‬ﺳﺎﻋﺔ ﻓﻲ دراﺳﺔ ﺟﺮﻋﺔ واﺣﺪة‬
‫]‪[118‬‬
‫ﻟﻤﺮﺿﻰ اﻟﺴﻜﺮ(‪.‬‬

‫ّ‬
‫اﻷدﻟﺔ إﻟﻰ أن ﺗﺮﻛﻴﺰات اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻓﻲ اﻟﻜﺒﺪ ﻓﻲ اﻟﺒﺸﺮ ﻗﺪ ﺗﻜﻮن أﻋﻠﻰ ﺑﻤﺮﺗﻴﻦ إﻟﻰ ﺛﻼث ﻣﺮات ﻣﻦ ﺗﺮﻛﻴﺰات اﻟﺒﻼزﻣﺎ‬ ‫ﺗﺸﻴﺮ ﺑﻌﺾ‬
‫]‪[119‬‬
‫وﻫﺬا ﻳﻜﻮن ﺑﺴﺒﺐ اﻣﺘﺼﺎص اﻟﻮرﻳﺪ اﻟﺒﺎﺑﻲ واﻣﺘﺼﺎص اﻟﻜﺒﺪ إذا أﺧﺬ ﻋﻦ ﻃﺮﻳﻖ اﻟﻔﻢ‪.‬‬

‫اﻟﺘﺮﻛﻴﺐ اﻟﻜﻴﻤﻴﺎﺋﻲ‬

‫ﻣﻴﺘﻔﻮرﻣﻴﻦ ﻫﻴﺪروﻛﻠﻮرﻳﺪ )‪-1،1‬ﺛﻨﺎﺋﻲ ﻣﻴﺜﻴﻞ ﺑﻴﺠﻮاﻧﻴﺪ ﻫﻴﺪروﻛﻠﻮرﻳﺪ( ﻗﺎﺑﻞ ﻟﻠﺬوﺑﺎن ﻓﻲ اﻟﻤﺎء ﺑﺤﺮﻳّ ﺔ‪ ،‬ﻗﺎﺑﻞ ﻟﻠﺬوﺑﺎن ﺑﺸﻜﻞ‬
‫ﻃﻔﻴﻒ ﻓﻲ اﻹﻳﺜﺎﻧﻮل‪ ،‬وﻟﻜﻨﻪ ﻏﻴﺮ ﻗﺎﺑﻞ ﻟﻠﺬوﺑﺎن ﺗﻘﺮﻳ ًﺒﺎ ﻓﻲ اﻷﺳﻴﺘﻮن أو اﻷﺛﻴﺮ أو اﻟﻜﻠﻮروﻓﻮرم‪ .‬ﻗﻴﻤﺔ ‪ pKa‬ﻟﻠﻤﻴﺘﻔﻮرﻣﻴﻦ ‪.12.4‬‬
‫]‪[119‬‬
 ‫ﻳﺘﻀﻤﻦ اﻟﺘﺮﻛﻴﺐ اﻟﻤﻌﺘﺎد ﻟﻠﻤﻴﺘﻔﻮرﻣﻴﻦ اﻟﻤﻮﺻﻮف ﻓﻲ اﻷﺻﻞ ﻋﺎم ‪ ،1922‬ﺗﻔﺎﻋﻞ وﻋﺎء واﺣﺪ ﻣﻦ ﺛﻨﺎﺋﻲ ﻣﻴﺜﻴﻞ أﻣﻴﻦ‬
‫]‪[121][120‬‬
‫ﻫﻴﺪروﻛﻠﻮرﻳﺪ و ‪-2‬ﺳﻴﺎﻧﻮﺟﻮاﻧﻴﺪﻳﻦ ﻋﻠﻰ اﻟﺤﺮارة‪.‬‬

‫ً‬
‫وﻓﻘﺎ ﻟﻺﺟﺮاء اﻟﻤﻮﺻﻮف ﻓﻲ ﺑﺮاءة اﺧﺘﺮاع آرون ﻟﻌﺎم ‪ [122]،1975‬وﻣﻮﺳﻮﻋﺔ اﻟﺘﺼﻨﻴﻊ اﻟﺪواﺋﻲ‪ [123]،‬ﻳﺘﻢ إذاﺑﺔ ﻛﻤﻴﺎت ﻣﺘﺴﺎوﻳﺔ‬
‫اﻟﻤﻮﻻت ﻣﻦ ﺛﻨﺎﺋﻲ ﻣﻴﺜﻴﻞ أﻣﻴﻦ و ‪-2‬ﺳﻴﺎﻧﻮﺟﻮاﻧﻴﺪﻳﻦ ﻓﻲ اﻟﺘﻮﻟﻮﻳﻦ ﻣﻊ اﻟﺘﺒﺮﻳﺪ ﻟﺘﻜﻮﻳﻦ ﻣﺤﻠﻮل ﻣﺮﻛﺰ‪ ،‬وﻳﺘﻢ إﺿﺎﻓﺔ ﻛﻤﻴﺔ ﻣﺘﺴﺎوﻳﺔ‬
‫ﺑﺎﻟﻤﻮﻻت ﻣﻦ ﻛﻠﻮرﻳﺪ اﻟﻬﻴﺪروﺟﻴﻦ ﺑﺒﻂء‪ .‬ﻳﺒﺪأ اﻟﺨﻠﻴﻂ ﻓﻲ اﻟﻐﻠﻴﺎن ﻣﻦ ﺗﻠﻘﺎء ﻧﻔﺴﻪ‪ ،‬وﺑﻌﺪ اﻟﺘﺒﺮﻳﺪ‪ ،‬ﻳﺘﺮﺳﺐ ﻫﻴﺪروﻛﻠﻮرﻳﺪ‬
‫اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﺑﻨﺴﺒﺔ ‪.٪96‬‬

‫اﻟﻤﺸﺘﻘﺎت‬
‫ﻋ…‬
‫اﻟﻤﺸﺘﻖ اﻟﺠﺪﻳﺪ ‪ ،HL156A‬اﻟﻤﻌﺮوف ً‬
‫أﻳﻀﺎ ﺑﺎﺳﻢ ‪ ،IM156‬ﻫﻮ دواء ﺟﺪﻳﺪ ﻣﺤﺘﻤﻞ ﻟﻼﺳﺘﺨﺪام‬
‫اﻟﻄﺒﻲ‪[129][128][127][126][125][124].‬‬

‫ﺗﺎرﻳﺦ اﻟﻤﻴﺘﻔﻮرﻣﻦ‬

‫ُﺻﻨﻒ اﻟﺒﻴﻐﻮاﻧﻴﺪ ﻣﻦ اﻷدوﻳﺔ اﻟﻤﻀﺎدة ﻟﻤﺮض اﻟﺴﻜﺮ‪ ،‬واﻟﺬي ﻳﺸﻤﻞ ً‬

‫أﻳﻀﺎ اﻟﻌﻮاﻣﻞ اﻟﻤﺴﺤﻮﺑﺔ اﻟﻔﻴﻨﻔﻮرﻣﻴﻦ واﻟﺒﻮﻓﻮرﻣﻴﻦ‪ ،‬ﻳﻨﺸﺄ ﻣﻦ‬
‫اﻟﻠﻴﻠﻚ اﻟﻔﺮﻧﺴﻲ أو ﺷﺎرع اﻟﻤﺎﻋﺰ)ﻣﺪرة ﻣﺨﺰﻧﻴﺔ(‪ ،‬وﻫﻮ ﻧﺒﺎت ﻳﺴﺘﺨﺪم ﻓﻲ اﻟﻄﺐ اﻟﺸﻌﺒﻲ ﻟﻌﺪة ﻗﺮون‪ [130].‬اﻟﻤﺪرة اﻟﻤﺨﺰﻧﻴﺔ ﻧﻔﺴﻬﺎ‬
‫ﻻ ﺗﺤﺘﻮي ﻋﻠﻰ أي ﻣﻦ ﻫﺬه اﻷدوﻳﺔ‪ ،‬وﻟﻜﻦ إﻳﺰو أﻣﻴﻠﻴﻦ ﻏﻮاﻧﻴﺪﻳﻦ؛ اﻟﻔﻴﻨﻔﻮرﻣﻴﻦ واﻟﺒﻮﻓﻮرﻣﻴﻦ واﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻫﻲ ﻣﺮﻛﺒﺎت ﻣﺨﻠﻘﺔ‬
‫اﻟﻨﺒﺎت‪[130].‬‬ ‫ﻛﻴﻤﻴﺎﺋﻴﺎ ﺗﺘﻜﻮن ﻣﻦ ﺟﺰﻳﺌﻴﻦ ﻏﻮاﻧﻴﺪﻳﻦ‪ ،‬وﻫﻲ أﻛﺜﺮ دﻫﻨًﺎ ﻣﻦ اﻟﻤﺮﻛﺐ اﻷﺻﻠﻲ اﻟﻤﺸﺘﻖ ﻣﻦ‬
‫ً‬

‫ﺗﻢ وﺻﻒ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻷول ﻣﺮة ﻓﻲ اﻷدﺑﻴﺎت اﻟﻌﻠﻤﻴﺔ ﻓﻲ ﻋﺎم ‪ ،1922‬ﺑﻮاﺳﻄﺔ اﻣﻴﻞ ﻓﻴﺮﻧﺮ وﺟﻴﻤﺲ ﺑﻴﻞ‪ ،‬ﻛﻤﻨﺘﺞ ﻓﻲ ﺗﺨﻠﻴﻖ‬
‫ﺛﻨﺎﺋﻲ ﻣﻴﺜﻴﻞ ﻏﻮاﻧﻴﺪﻳﻦ )‪ [120].(N,N-dimethylguanidine‬ﻓﻲ ﻋﺎم ‪ ،1929‬اﻛﺘﺸﻒ ﺳﻠﻮﺗﺎ وﺷﻴﺶ ﺗﺄﺛﻴﺮه ﻓﻲ ﺧﻔﺾ اﻟﺴﻜﺮ‬
‫ﻓﻲ اﻷراﻧﺐ‪ ،‬ووﺟﺪا أﻧﻪ أﻗﻮى ﻣﻀﺎد ﻟﻠﺒﻴﻐﻮاﻧﻴﺪ ﻗﺎﻣﻮا ﺑﺪراﺳﺘﻪ‪ [131].‬ﺗﻢ ﻧﺴﻴﺎن ﻫﺬه اﻟﻨﺘﻴﺠﺔ ً‬
‫ﺗﻤﺎﻣﺎ‪ ،‬ﺣﻴﺚ اﺳﺘﺤﻮذت ﻧﻈﺎﺋﺮ‬
‫]‪[132‬‬
‫اﻟﻐﻮاﻧﻴﺪﻳﻦ اﻷﺧﺮى ﻣﺜﻞ ﺳﻴﻨﺜﺎﻟﻴﻦ )دواء ﻓﻤﻮي ﻣﻀﺎد ﻟﻤﺮض اﻟﺴﻜﺮي( ﻋﻠﻰ ﻧﻔﺴﻬﺎ وﺳﺮﻋﺎن ﻣﺎ ﻃﻐﻰ اﻷﻧﺴﻮﻟﻴﻦ ﻋﻠﻴﻬﺎ‪.‬‬

‫اﺳﺘﺆﻧﻒ اﻻﻫﺘﻤﺎم ﺑﺎﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻓﻲ ﻧﻬﺎﻳﺔ اﻷرﺑﻌﻴﻨﻴﺎت‪ .‬ﻓﻲ ﻋﺎم ‪ ،1950‬وﺟﺪ أن اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‪ ،‬ﻋﻠﻰ ﻋﻜﺲ ﺑﻌﺾ اﻟﻤﺮﻛﺒﺎت‬
‫اﻟﻤﻤﺎﺛﻠﺔ اﻷﺧﺮى‪ ،‬ﻻ ﻳﻘﻠﻞ ﻣﻦ ﺿﻐﻂ اﻟﺪم وﻣﻌﺪل ﺿﺮﺑﺎت اﻟﻘﻠﺐ ﻓﻲ اﻟﺤﻴﻮاﻧﺎت‪ [133].‬ﻓﻲ ذﻟﻚ اﻟﻌﺎم‪ ،‬اﺳﺘﺨﺪم اﻟﻄﺒﻴﺐ اﻟﻔﻠﺒﻴﻨﻲ‬
‫أوزﻳﺒﻴﻮ واي ﺟﺎرﺳﻴﺎ ]‪[134‬اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ )أﻃﻠﻖ ﻋﻠﻴﻪ اﺳﻢ ﻓﻼﻣﻴﻦ( ﻟﻌﻼج اﻹﻧﻔﻠﻮﻧﺰا‪ .‬وأﺷﺎر إﻟﻰ أن اﻟﺪواء "ﺧﻔﺾ ﻧﺴﺒﺔ اﻟﺴﻜﺮ‬
‫ﺳﺎﻣﺎ‪ .‬ﻳﻌﺘﻘﺪ ﺟﺎرﺳﻴﺎ أن اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻟﻪ ﺗﺄﺛﻴﺮ ﻣﻀﺎد ﻟﻠﺠﺮاﺛﻴﻢ‪ ،‬وﻣﻀﺎد‬
‫ﻓﻲ اﻟﺪم إﻟﻰ اﻟﺤﺪ اﻷدﻧﻰ اﻟﻔﺴﻴﻮﻟﻮﺟﻲ" وﻟﻢ ﻳﻜﻦ ً‬
‫ﻟﻠﻔﻴﺮوﺳﺎت‪ ،‬وﻣﻀﺎد ﻟﻠﻤﻼرﻳﺎ‪ ،‬وﺧﺎﻓﺾ ﻟﻠﺤﺮارة‪ ،‬وﻣﺴﻜﻦ‪ [135].‬ﻓﻲ ﺳﻠﺴﻠﺔ ﻣﻦ اﻟﻤﻘﺎﻻت ﻓﻲ ﻋﺎم ‪ ،1954‬ﻟﻢ ﻳﺘﻤﻜﻦ ﻋﺎﻟﻢ اﻟﺼﻴﺪﻟﺔ‬
‫اﻟﺒﻮﻟﻨﺪي ﻳﺎﻧﻮش ﺳﻮﺑﻨﻴﻮﺳﻜﻲ ﻣﻦ ﺗﺄﻛﻴﺪ ﻣﻌﻈﻢ ﻫﺬه اﻟﺘﺄﺛﻴﺮات‪ [136]،‬ﺑﻤﺎ ﻓﻲ ذﻟﻚ اﻧﺨﻔﺎض ﻧﺴﺒﺔ اﻟﺴﻜﺮ ﻓﻲ اﻟﺪم‪ .‬وﺑﺪﻻً ﻣﻦ ذﻟﻚ‪،‬‬
‫]‪[138][137‬‬
‫ﻻﺣﻆ اﻟﺘﺄﺛﻴﺮات اﻟﻤﻀﺎدة ﻟﻠﻔﻴﺮوﺳﺎت ﻋﻠﻰ اﻟﺒﺸﺮ‪.‬‬
 ‫درس اﺧﺘﺼﺎﺻﻲ اﻟﺴﻜﺮي اﻟﻔﺮﻧﺴﻲ ﺟﺎن ﺳﺘﻴﺮن اﻟﺨﺼﺎﺋﺺ اﻟﻤﻀﺎدة ﻟﻔﺮط ﺳﻜﺮ اﻟﺪم ﻓﻲ اﻟﺠﺎﻟﻴﺠﻴﻦ‪ ،‬وﻫﻮ ﻗﻠﻮﻳﺪ ﻣﻌﺰول ﻣﻦ‬
‫اﻟﻤﺪرة اﻟﻤﺨﺰﻧﻴﺔ‪ ،‬واﻟﺬي ﻳﺮﺗﺒﻂ ﻓﻲ ﺗﺮﻛﻴﺒﺘﻪ ﺑﺎﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‪ ،‬وﺷﻬﺪ اﺳﺘﺨﺪاﻣﻪ ﻟﻔﺘﺮة وﺟﻴﺰة ﻛﻤﻀﺎد ﻟﻤﺮض اﻟﺴﻜﺮ ﻗﺒﻞ ﺗﻄﻮﻳﺮ‬
‫ﻣﺮﻛﺒﺎت ﺳﻴﻨﺜﺎﻟﻴﻦ‪ [139].‬ﻓﻲ وﻗﺖ ﻻﺣﻖ‪ ،‬أﺛﻨﺎء ﻋﻤﻠﻪ ﻓﻲ ﻣﺨﺘﺒﺮات آرون ﻓﻲ ﺑﺎرﻳﺲ‪ ،‬دﻓﻌﻪ ﺗﻘﺮﻳﺮ ﻏﺎرﺳﻴﺎ إﻟﻰ إﻋﺎدة اﻟﺘﺤﻘﻴﻖ ﻓﻲ‬
‫ﻧﺸﺎط ﺧﻔﺾ ﻧﺴﺒﺔ اﻟﺴﻜﺮ ﻓﻲ اﻟﺪم ﻟﻠﻤﻴﺘﻔﻮرﻣﻴﻦ واﻟﻌﺪﻳﺪ ﻣﻦ ﻧﻈﺎﺋﺮ اﻟﺒﻴﻐﻮاﻧﻴﺪ‪ .‬ﻛﺎن ﺳﺘﻴﺮن أول ﻣﻦ ﺟﺮب اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻋﻠﻰ‬
‫‪[139][132].1957‬‬ ‫اﻟﺒﺸﺮ ﻟﻌﻼج ﻣﺮض اﻟﺴﻜﺮي‪ .‬ﺻﺎغ اﺳﻢ "ﺟﻠﻮﻛﻮﻓﺎج" )آﻛﻞ اﻟﺠﻠﻮﻛﻮز( ﻟﻠﺪواء وﻧﺸﺮ ﻧﺘﺎﺋﺠﻪ ﻓﻲ ﻋﺎم‬

‫ﻣﺘﺎﺣﺎ ﻓﻲ اﻟﻮﺻﻔﺎت اﻟﻮﻃﻨﻴﺔ اﻟﺒﺮﻳﻄﺎﻧﻴﺔ ﻓﻲ ﻋﺎم ‪ .1958‬ﺗﻢ ﺑﻴﻌﻪ ﻓﻲ اﻟﻤﻤﻠﻜﺔ اﻟﻤﺘﺤﺪة ﻣﻦ ﻗﺒﻞ ﺷﺮﻛﺔ‬
‫ً‬ ‫أﺻﺒﺢ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‬
‫روﻧﺎ‪[140].‬‬ ‫ﻓﺮﻋﻴﺔ ﺻﻐﻴﺮة ﺗﺎﺑﻌﺔ ﻟﺸﺮﻛﺔ آرون ﺗﺪﻋﻰ‬

‫ﻟﻢ ﻳﺘﻢ إﺣﻴﺎء اﻻﻫﺘﻤﺎم اﻟﻮاﺳﻊ ﺑﺎﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﺣﺘﻰ اﻧﺴﺤﺎب ﻣﺮﻛﺒﺎت اﻟﺒﻴﻐﻮاﻧﻴﺪات اﻷﺧﺮى ﻓﻲ اﻟﺴﺒﻌﻴﻨﻴﺎت‪ .‬ﺗﻤﺖ اﻟﻤﻮاﻓﻘﺔ ﻋﻠﻰ‬
‫اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻓﻲ ﻛﻨﺪا ﻓﻲ ﻋﺎم ‪ [141]،1972‬وﻟﻜﻦ ﻟﻢ ﻳﺘﻢ اﻟﺤﺼﻮل ﻋﻠﻰ ﻣﻮاﻓﻘﺔ ﻣﻦ إدارة اﻟﻐﺬاء واﻟﺪواء اﻷﻣﺮﻳﻜﻴﺔ )‪(FDA‬‬
‫ﻟﻤﺮض اﻟﺴﻜﺮي ﻣﻦ اﻟﻨﻮع ‪ 2‬ﺣﺘﻰ ﻋﺎم ‪ [142].1994‬ﺗﻢ إﻧﺘﺎج ﺑﻤﻮﺟﺐ ﺗﺮﺧﻴﺺ ﻣﻦ ﺑﺮﻳﺴﺘﻮل‪-‬ﻣﺎﻳﺮز ﺳﻜﻮﻳﺐ‪ ،‬وﻛﺎن أول ﺗﺮﻛﻴﺒﺔ‬
‫ﺑﺪءا ﻣﻦ ‪ 3‬ﻣﺎرس ‪ [143].1995‬ﺗﺘﻮﻓﺮ اﻟﺘﺮﻛﻴﺒﺎت‬
‫ﺗﺤﻤﻞ ﻋﻼﻣﺔ ﺗﺠﺎرﻳﺔ ﻟﻠﻤﻴﺘﻔﻮرﻣﻴﻦ ﻳﺘﻢ ﺗﺴﻮﻳﻘﻬﺎ ﻓﻲ اﻟﻮﻻﻳﺎت اﻟﻤﺘﺤﺪة‪ً ،‬‬
‫اﻟﺠﻨﻴﺴﺔ اﻵن ﻓﻲ اﻟﻌﺪﻳﺪ ﻣﻦ اﻟﺒﻠﺪان‪ ،‬وﻳُ ﻌﺘﻘﺪ أن اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ أﺻﺒﺢ أﻛﺜﺮ اﻷدوﻳﺔ اﻟﻤﻀﺎدة ﻟﻤﺮض اﻟﺴﻜﺮ اﻟﻤﻮﺻﻮﻓﺔ ﻋﻠﻰ ﻧﻄﺎق‬
‫اﻟﻌﺎﻟﻢ‪[139].‬‬ ‫واﺳﻊ ﻓﻲ‬

‫اﻟﻤﺠﺘﻤﻊ واﻟﺜﻘﺎﻓﺔ‬

‫ﺑﻴﺌﻲ‬
‫ﻋ…‬
‫ﻋﺜﺮ ﻋﻠﻰ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ وﻣﻨﺘﺞ اﻟﺘﺤﻮل اﻟﺮﺋﻴﺴﻲ ﺟﻮاﻧﻴﻠﻮرﻳﺎ ﻓﻲ اﻟﻨﻔﺎﻳﺎت اﻟﺴﺎﺋﻠﺔ ﻟﻤﺤﻄﺔ ﻣﻌﺎﻟﺠﺔ ﻣﻴﺎه اﻟﺼﺮف اﻟﺼﺤﻲ واﻛﺘﺸﻔﺎ‬
‫ﺑﺎﻧﺘﻈﺎم ﻓﻲ اﻟﻤﻴﺎه اﻟﺴﻄﺤﻴﺔ‪ .‬ﻗﻴﺴﺖ ﺗﺮﻛﻴﺰات ﻛﺒﺮﻳﺘﺎت ﺟﻮاﻧﻴﻞ ﻓﻮق ‪ 200‬ﻣﻴﻜﺮوﻏﺮام‪ /‬ﻟﺘﺮ ﻓﻲ أﺣﺪ اﻷﻧﻬﺎر اﻷﻟﻤﺎﻧﻴﺔ‪ ،‬واﻟﺘﻲ ﺗﻌﺪ‬
‫]‪[144‬‬ ‫ﻣﻦ ﺑﻴﻦ أﻋﻠﻰ اﻟﻤﻌﺪﻻت اﻟﺘﻲ أﺑﻠﻎ ﻋﻨﻬﺎ ﻟﻤﻨﺘﺠﺎت اﻟﺘﺤﻮﻳﻞ اﻟﺼﻴﺪﻻﻧﻲ ﻓﻲ اﻟﺒﻴﺌﺎت اﻟﻤﺎﺋﻴﺔ‪.‬‬

‫ﺗﺮﻛﻴﺒﺎت‬
‫ﻋ…‬

‫أﻗﺮاص ﻣﻴﺘﻔﻮرﻣﻴﻦ ‪ ٥٠٠‬ﻣﻠﻎ اﻟﺠﻨﻴﺴﺔ ‪ ،‬ﻛﻤﺎ ﺗﺒﺎع ﻓﻲ اﻟﻤﻤﻠﻜﺔ اﻟﻤﺘﺤﺪة‪.‬‬

 ‫اﺳﻢ "ﻣﻴﺘﻔﻮرﻣﻴﻦ" ﻫﻮ )اﺳﻢ ﻣﻌﺘﻤﺪ ﺑﺮﻳﻄﺎﻧﻲ‪ ،‬اﺳﻢ ﻣﻌﺘﻤﺪ أﻣﺮﻳﻜﻲ‪ ،‬اﺳﻢ دوﻟﻲ ﻏﻴﺮ ﻣﺴﺠﻞ اﻟﻤﻠﻜﻴﺔ( ﻟﻬﺬا اﻟﺪواء‪ُ ،‬ﻳ ّ‬
‫ﺴﻮق ﺑﺄﺳﻤﺎء‬
‫ﺗﺠﺎرﻳﺔ ﻋﺪﻳﺪة ﻣﻨﻬﺎ ﺟﻠﻮﻛﻮﻓﺎج‪ ،‬وﺟﻠﻮﻛﻮﻣﻴﻦ‪ ،‬وﻣﻴﺘﻔﻮرال‪ ،‬وﺳﻴﻮﻓﻮر‪ ،‬ودﻳﺎﻟﻮن‪ ،‬وﺑﺮوت‪ ،‬وﻛﺎرﺑﻮﻓﺎج‪ ،‬ورﻳﻮﻣﻴﺖ‪ ،‬وﻓﻮرﻣﻴﺖ‪،‬‬
‫وﻓﻮرﺗﺎﻣﻴﺖ‪ ،‬وﻏﻠﻮﻣﺘﺰا‪ ،‬وأوﺑﻴﻤﺖ‪ ،‬وﻏﻠﻮﻓﻮرﻣﻴﻦ‪ ،‬ودﻳﺎﻧﺒﻴﻦ‪ ،‬ودﻳﺎﺑﻴﻜﺲ‪ ،‬ودﻳﺎﻓﻮرﻣﻴﻦ‪ ،‬وﻣﻴﺘﻔﻮﻏﺎﻣﺎ]‪ [146][145‬ﻫﻨﺎك اﻟﻌﺪﻳﺪ ﻣﻦ‬
‫ﺗﺮﻛﻴﺒﺎت اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ اﻟﻤﺘﺎﺣﺔ ﻓﻲ اﻟﺴﻮق ﺑﺎﺳﺘﺜﻨﺎء اﻟﺸﻜﻞ اﻟﺴﺎﺋﻞ ﻟﻬﺎ ﻣﻌﺎدﻻت ﻋﺎﻣﺔ‪ [37] .‬ﻳﺘﻮﻓﺮﻣﻴﺘﻔﻮرﻣﻴﻦ اي ار )اﻹﺻﺪار‬
‫اﻟﻔﻮري( ﻓﻲ أﻗﺮاص ‪ 500‬و‪ 850‬و‪ 1000‬ﻣﺠﻢ‪ ،‬ﺑﻴﻨﻤﺎ ﻳﺘﻮﻓﺮ ﻣﻴﺘﻔﻮرﻣﻴﻦ اﻛﺲ ار )اﻹﺻﺪار اﻟﻤﻤﺘﺪ( ﺑﻨﻘﺎط ﻗﻮة ‪ 500‬و‪750‬‬
‫و‪ 1000‬ﻣﻠﻎ )ﻳﺒﺎع ً‬
‫أﻳﻀﺎ ﺑﺎﺳﻢ ﻓﻮرﺗﺎﻣﻴﺖ وﻏﻠﻮﻣﺘﺰاوﻏﻠﻮﻓﻮرﻣﻴﻦ ﻓﻲ اﻟﻮﻻﻳﺎت اﻟﻤﺘﺤﺪة(‪ .‬إن اﺳﺘﺨﺪام ﺗﺮﻛﻴﺒﺔ ﻣﻤﺘﺪة اﻟﻤﻔﻌﻮل‬
‫ﻫﻮ ﻟﻤﻮاﺟﻬﺔ اﻵﺛﺎر اﻟﺠﺎﻧﺒﻴﺔ اﻟﻤﻌﺪﻳﺔ اﻟﻤﻌﻮﻳﺔ اﻟﺸﺎﺋﻌﺔ‪ ،‬ﺑﺎﻹﺿﺎﻓﺔ إﻟﻰ زﻳﺎدة اﻻﻣﺘﺜﺎل ﻋﻦ ﻃﺮﻳﻖ ﺗﻘﻠﻴﻞ ﻋﺐء ﺣﺒﻮب ﻣﻨﻊ اﻟﺤﻤﻞ‬
‫وﺑﺎﻟﺘﺎﻟﻲ ﻳﻤﻜﻦ ﺗﺤﺴﻴﻦ اﻻﻟﺘﺰا ﻋﻠﻰ ﺣﺴﺎب اﻟﺤﺠﻢ اﻷﻛﺒﺮ ﻟﻠﺤﺒﺔ‪ .‬ﻳﺘﻮﻓﺮ ً‬
‫أﻳﻀﺎ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ اﻟﺴﺎﺋﻞ )ﻳُ ﺒﺎع ﻓﻘﻂ ﻋﻠﻰ ﺷﻜﻞ رﻳﻮﻣﻴﺖ‬
‫ﻓﻲ اﻟﻮﻻﻳﺎت اﻟﻤﺘﺤﺪة(‪ ،‬ﺣﻴﺚ ﻳﺤﺘﻮي ‪ 5‬ﻣﻞ ﻣﻦ اﻟﻤﺤﻠﻮل ﻋﻠﻰ ﻧﻔﺲ ﻛﻤﻴﺔ اﻟﺪواء ﻣﺜﻞ ﻗﺮص ‪ 500‬ﻣﺠﻢ‪ .‬ﻳﻤﻜﻦ أن ﻳﻜﻮن‬
‫اﺳﺘﺨﺪام اﻟﺸﻜﻞ اﻟﺴﺎﺋﻞ ﻣﻔﻴﺪً ا ﻓﻲ ﻣﺴﺎﻋﺪة أوﻟﺌﻚ اﻟﺬﻳﻦ ﻳﻌﺎﻧﻮن ﻣﻦ ﻣﺸﺎﻛﻞ اﻟﺒﻠﻊ اﻟﺠﺴﺪﻳﺔ أو اﻟﻨﻔﺴﻴﺔ ﻋﻠﻰ ﺗﻨﺎول اﻟﺪواء‪ ،‬أو‬
‫ﺗﻘﻠﻴﻞ ﻋﺪد اﻟﺨﻄﻮات اﻟﻼزﻣﺔ ﻟﺘﻨﺎول اﻟﺪواء‪.‬‬

‫ﻋ…‬
‫اﻟﺪﻣﺞ ﻣﻊ أدوﻳﺔ أﺧﺮى‬

‫ﻋﻨﺪ اﺳﺘﺨﺪاﻣﻪ ﻟﻤﺮض اﻟﺴﻜﺮي اﻟﻨﻤﻂ اﻟﺜﺎﻧﻲ‪ ،‬ﻏﺎﻟ ًﺒﺎ ﻣﺎ ﻳﻮﺻﻒ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﺑﺎﻻﺷﺘﺮاك ﻣﻊ أدوﻳﺔ أﺧﺮى‪ .‬ﻳﺘﻮﻓﺮ اﻟﻌﺪﻳﺪ ﻣﻨﻬﺎ‬
‫]‪[148] [147‬‬ ‫ﻛﻤﺠﻤﻮﻋﺎت ﺟﺮﻋﺔ ﺛﺎﺑﺘﺔ‪ ،‬ﻣﻊ إﻣﻜﺎﻧﻴﺔ ﺗﻘﻠﻴﻞ ﻋﺐء ﺣﺒﻮب ﻣﻨﻊ اﻟﺤﻤﻞ وﺗﻘﻠﻴﻞ اﻟﺘﻜﻠﻔﺔ وﺗﺒﺴﻴﻂ اﻹدارة‪.‬‬

‫روﺳﻴﻐﻠﻴﺘﺎزون‬
‫ﻋ…‬
‫اﻛﺘﺸﻒ ﻣﺰﻳﺞ ﻣﻦ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ وروزﻳﻐﻠﻴﺘﺎزون ﻓﻲ ﻋﺎم ‪ ،2002‬وﺑﻴﻌﺖ ﻛﺄﻓﺎﻧﺪاﻣﻴﺖ )‪ (Avandamet‬ﻣﻦ ﺷﺮﻛﺔ ﺟﻼﻛﺴﻮ‬
‫ﺳﻤﻴﺚ ﻛﻼﻳﻦ‪ [149]،‬أو دواء ﻋﺎم‪ [150].‬ﺑﺼﻴﻐﺔ ‪ 500/1‬و‪ 500/2‬و‪ 500/4‬و‪ 1000/2‬و‪ 1000‬ﻣﻠﻎ‪ 4 /‬ﻣﻠﻎ ﻣﻦ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‪/‬‬
‫]‪[151‬‬
‫روزﻳﻐﻠﻴﺘﺎزون‪ .‬ﺑﺤﻠﻮل ﻋﺎم ‪ ،2009‬أﺻﺒﺢ ﻣﺰﻳﺞ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ اﻷﻛﺜﺮ ﺷﻌﺒﻴﺔ‪.‬‬

‫ﻓﻲ ﻋﺎم ‪ ،2005‬ﺗﻤﺖ إزاﻟﺔ ﻣﺨﺰون أﻓﺎﻧﺪاﻣﻴﺖ ﻣﻦ اﻟﺴﻮق‪ ،‬ﺑﻌﺪ أن أﻇﻬﺮت ﻋﻤﻠﻴﺎت اﻟﺘﻔﺘﻴﺶ أن اﻟﻤﺼﻨﻊ اﻟﺬي أﻧﺘﺠﻪ ﻳﻨﺘﻬﻚ‬
‫ﻣﺘﺎﺣﺎ ﻣﺮة أﺧﺮى ﺑﺤﻠﻮل ﻧﻬﺎﻳﺔ‬
‫ً‬ ‫ﻣﻤﺎرﺳﺎت اﻟﺘﺼﻨﻴﻊ اﻟﺠﻴﺪة‪ [152].‬اﺳﺘﻤﺮ وﺻﻒ زوج اﻟﺪواء ﺑﺸﻜﻞ ﻣﻨﻔﺼﻞ‪ ،‬وأﺻﺒﺢ أﻓﺎﻧﺪاﻣﻴﺖ‬
‫ذﻟﻚ اﻟﻌﺎم‪ .‬ﺣﺼﻠﺖ ﺗﺮﻛﻴﺒﺔ ﻋﺎﻣﺔ ﻣﻦ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‪ /‬روزﻳﻐﻠﻴﺘﺎزون ﻣﻦ ﺷﺮﻛﺔ ﺗﻴﻔﺎ ﻋﻠﻰ ﻣﻮاﻓﻘﺔ ﻣﺒﺪﺋﻴﺔ ﻣﻦ إدارة اﻟﻐﺬاء واﻟﺪواء‬
‫‪[153].2012‬‬ ‫اﻷﻣﺮﻳﻜﻴﺔ ووﺻﻠﺖ إﻟﻰ اﻟﺴﻮق ﻓﻲ أواﺋﻞ ﻋﺎم‬

‫ﻣﻊ ذﻟﻚ‪ ،‬ﺑﻌﺪ اﻟﺘﺤﻠﻴﻞ اﻟﺘﻠﻮي ﻓﻲ ﻋﺎم ‪ 2007‬اﻟﺬي رﺑﻂ اﺳﺘﺨﺪام اﻟﺪواء ﺑﺰﻳﺎدة ﺧﻄﺮ اﻹﺻﺎﺑﺔ ﺑﻨﻮﺑﺔ ﻗﻠﺒﻴﺔ‪ [154]،‬أﺛﻴﺮت ﻣﺨﺎوف‬
‫ﺑﺸﺄن ﺳﻼﻣﺔ اﻷدوﻳﺔ اﻟﺘﻲ ﺗﺤﺘﻮي ﻋﻠﻰ روزﻳﺠﻠﻴﺘﺎزون‪ .‬ﻓﻲ ﺳﺒﺘﻤﺒﺮ ‪ ،2010‬أوﺻﺖ وﻛﺎﻟﺔ اﻷدوﻳﺔ اﻷوروﺑﻴﺔ ﺑﺘﻌﻠﻴﻖ اﻟﺪواء ﻣﻦ‬
‫]‪[156][155‬‬
‫اﻟﺴﻮق اﻷوروﺑﻴﺔ ﻷن ﻓﻮاﺋﺪ اﻟﺮوزﻳﻐﻠﻴﺘﺎزون ﻟﻢ ﺗﻌﺪ ﺗﻔﻮق اﻟﻤﺨﺎﻃﺮ‪.‬‬

‫ﺳﺤﺐ ﻣﻦ اﻟﺴﻮق ﻓﻲ اﻟﻤﻤﻠﻜﺔ اﻟﻤﺘﺤﺪة واﻟﻬﻨﺪ ﻓﻲ ﻋﺎم ‪ [157]،2010‬وﻓﻲ ﻧﻴﻮزﻳﻠﻨﺪا وﺟﻨﻮب إﻓﺮﻳﻘﻴﺎ ﻓﻲ ﻋﺎم ‪ [158].2011‬ﻣﻦ‬
‫ﻧﻮﻓﻤﺒﺮ ‪ 2011‬ﺣﺘﻰ ﻧﻮﻓﻤﺒﺮ ‪ [159]،2013‬ﺑﺒﻴﻊ روزﻳﻌﻠﻴﺘﺎزون أو ﻣﻴﺘﻔﻮرﻣﻴﻦ‪ /‬روزﻳﻐﻠﻴﺘﺎزون ﺑﺪون وﺻﻔﺔ ﻃﺒﻴﺔ؛ ﻋﻼوة ﻋﻠﻰ‬
‫ذﻟﻚ‪ُ ،‬ﻃﻠﺐ ﻣﻦ ﺻﺎﻧﻌﻲ اﻟﺪواء إﺧﻄﺎر اﻟﻤﺮﺿﻰ ﺑﺎﻟﻤﺨﺎﻃﺮ اﻟﻤﺮﺗﺒﻄﺔ ﺑﺎﺳﺘﺨﺪاﻣﻪ‪ ،‬وﻛﺎن ﻻ ﺑﺪ ﻣﻦ ﺷﺮاء اﻟﺪواء ﻋﻦ ﻃﺮﻳﻖ اﻟﺒﺮﻳﺪ ﻣﻦ‬
‫اﻟﻤﺤﺪدة‪[160].‬‬ ‫ﺧﻼل اﻟﺼﻴﺪﻟﻴﺎت‬
‫ﻓﻲ ﺗﺸﺮﻳﻦ اﻟﺜﺎﻧﻲ )ﻧﻮﻓﻤﺒﺮ( ‪ ،2013‬رﻓﻌﺖ إدارة اﻟﻐﺬاء واﻟﺪواء )‪ (FDA‬ﻗﻴﻮدﻫﺎ اﻟﺴﺎﺑﻘﺔ ﻋﻠﻰ روزﻳﻐﻠﻴﺘﺎزون ﺑﻌﺪ ﻣﺮاﺟﻌﺔ ﻧﺘﺎﺋﺞ‬
‫اﻟﺘﺠﺮﺑﺔ اﻟﺴﺮﻳﺮﻳﺔ ﻟﻌﺎم ‪ ) 2009‬ﺗﺠﺮﺑﺔ ﻣﺮاﻗﺒﺔ ﻋﺸﻮاﺋﻴﺔ ﻣﻔﺘﻮﺣﺔ اﻟﺘﺴﻤﻴﺔ ﻣﺪﺗﻬﺎ ﺳﺖ ﺳﻨﻮات(‪ ،‬واﻟﺘﻲ ﻓﺸﻠﺖ ﻓﻲ إﻇﻬﺎر ارﺗﻔﺎع‬
‫]‪[163][162][161‬‬
‫ﺧﻄﺮ اﻹﺻﺎﺑﺔ ﺑﻨﻮﺑﺔ ﻗﻠﺒﻴﺔ أو اﻟﻮﻓﺎة اﻟﻤﺮﺗﺒﻄﺔ ﺑﺄدوﻳﺔ‪.‬‬

‫ﺑﻴﻮﻏﻠﻴﺘﺎزون‬
‫ﻋ…‬
‫ﻣﺰﻳﺞ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ واﻟﺒﻴﻮﻏﻠﻴﺘﺎزون )أﻛﺘﻮﺑﻠﺲ ﻣﻴﺖ‪ ،‬ﺑﻴﻮﻣﻴﺖ‪ ،‬ﺑﻮﻟﻴﺘﻮ‪ ،‬ﻏﻠﻮﺑﺮاﻓﺎ( ﻣﺘﺎح ﻓﻲ اﻟﻮﻻﻳﺎت اﻟﻤﺘﺤﺪة واﻻﺗﺤﺎد‬
‫]‪[168][167][166][165][164‬‬
‫اﻷوروﺑﻲ‪.‬‬

‫ﻣﺜﺒﻂ ﺛﻨﺎﺋﻲ ﺑﺒﺘﻴﺪﻳﻞ ﺑﺒﺘﻴﺪاز‪4-‬‬

‫ﻋ…‬
‫ﻳﺜﺒﻂ ﻣﺜﺒﻄﺎت ﺛﻨﺎﺋﻲ ﺑﺒﺘﻴﺪﻳﻞ ﺑﺒﺘﻴﺪاز‪ 4-‬ودي ﺑﺒﺘﻴﻞ ﺑﺒﺘﻴﺪاز‪ 4 -‬وﺑﺎﻟﺘﺎﻟﻲ ﻳﻘﻠﻞ ﻣﺴﺘﻮﻳﺎت اﻟﺠﻠﻮﻛﺎﺟﻮن واﻟﺠﻠﻮﻛﻮز ﻓﻲ اﻟﺪم‪.‬‬
‫ﺗﺸﻤﻞ ﻣﺜﺒﻄﺎت ﻣﺜﺒﻄﺎت ﺛﻨﺎﺋﻲ ﺑﺒﺘﻴﺪﻳﻞ ﺑﺒﺘﻴﺪاز‪ 4-‬ﻣﻊ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻋﻠﻰ ﻣﺰﻳﺞ ﺳﻴﺘﺎﺟﻠﻴﺒﺘﻴﻦ‪/‬ﻣﻴﺘﻔﻮرﻣﻴﻦ‪ [170][169]،‬أﻟﻮﺟﻠﻴﺒﺘﻴﻦ‬
‫]‪[173‬‬ ‫)ﻛﺎزاﻧﻮ‪ ،‬ﻓﻴﺒﻮﻣﻴﺖ(‪ [172] [171] .‬ﻳﺴﻮق اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻣﻊ ﻟﻴﻨﺎﻏﻠﺒﺘﻴﻦ ﺗﺤﺖ اﻻﺳﻢ اﻟﺘﺠﺎري ﺟﻴﻨﺘﺎدﻳﻮﺗﻮ )‪.(Jentadueto‬‬
‫]‪[174‬‬

‫ﺳﻠﻔﻮﻧﻴﻞ ﻳﻮرﻳﺎ‬
‫ﻋ…‬
‫ﻳﻌﻤﻞ اﻟﺴﻠﻔﻮﻧﻴﻞ ﻳﻮرﻳﺎ ﻋﻦ ﻃﺮﻳﻖ زﻳﺎدة إﻓﺮاز اﻷﻧﺴﻮﻟﻴﻦ ﻣﻦ ﺧﻼﻳﺎ ﺑﻴﺘﺎ ﻓﻲ اﻟﺒﻨﻜﺮﻳﺎس‪ [175] .‬ﻏﺎﻟ ًﺒﺎ ﻣﺎ ﻳﻤﻜﻦ اﺳﺘﺨﺪاﻣﻬﺎ ﻛﻌﻼج‬
‫ﻓﻌﺎﻻ ﺑﺪرﺟﺔ ﻛﺎﻓﻴﺔ ﻓﻲ اﻟﻮﺻﻮل إﻟﻰ ﻣﺴﺘﻮﻳﺎت اﻟﺴﻜﺮ ﻓﻲ اﻟﺪم اﻟﻄﺒﻴﻌﻴﺔ‪ .‬اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‬ ‫ً‬ ‫ﺛﺎﻧﻮي إذا ﻟﻢ ﻳﻜﻦ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﺑﻤﻔﺮده‬
‫ﻣﺘﺎح ﻣﻊ اﻟﺴﻠﻔﻮﻧﻴﻞ ﻳﻮرﻳﺎ ﻏﻠﻴﺒﻴﺰﻳﺪ )‪ (Metaglip‬وﻏﻠﻴﺒﻴﻨﻜﻼﻣﻴﺪ )ﺑﺎﻟﻮﻻﻳﺎت اﻟﻤﺘﺤﺪة اﻷﻣﺮﻳﻜﻴﺔ‪ :‬ﻏﻠﻴﺒﻮرﻳﺪ()‪.(Glucovance‬‬
‫]‪[176‬‬
‫ﺗﺘﻮﻓﺮ اﻟﺘﺮﻛﻴﺒﺎت اﻟﻌﺎﻣﺔ ﻟﻠﻤﻴﺘﻔﻮرﻣﻴﻦ‪ /‬اﻟﻐﻠﻴﺒﻴﺰﻳﺪ واﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‪ /‬ﺟﻠﻴﺒﻨﻜﻼﻣﻴﺪ )اﻷﺧﻴﺮ أﻛﺜﺮ ﺷﻴﻮﻋً ﺎ(‪.‬‬

‫ﻣﻴﻐﻠﻴﺘﻴﻨﻴﺪ‬
‫ﻋ…‬
‫ﺗﺸﺒﻪ ﻣﻴﻐﻠﻴﺘﻴﻨﻴﺪ اﻟﺴﻠﻔﻮﻧﻴﻞ ﻳﻮرﻳﺎ‪ ،‬ﻷﻧﻬﺎ ﺗﺮﺗﺒﻂ ﺑﺨﻼﻳﺎ ﺑﻴﺘﺎ ﻓﻲ اﻟﺒﻨﻜﺮﻳﺎس‪ ،‬وﻟﻜﻨﻬﺎ ﺗﺨﺘﻠﻒ ﺣﺴﺐ ﻣﻮﻗﻊ اﻻرﺗﺒﺎط ﺑﺎﻟﻤﺴﺘﻘﺒﻞ‬
‫اﻟﻤﻘﺼﻮد وارﺗﺒﺎﻃﺎت اﻷدوﻳﺔ ﺑﺎﻟﻤﺴﺘﻘﺒﻞ‪ [175] .‬وﻧﺘﻴﺠﺔ ﻟﺬﻟﻚ‪ ،‬ﻓﺈن ﻣﺪة ﻣﻔﻌﻮﻟﻬﺎ أﻗﺼﺮ ﻣﻘﺎرﻧﺔ ﺑﺎﻟﺴﻠﻔﻮﻧﻴﻞ ﻳﻮرﻳﺎ‪ ،‬وﺗﺘﻄﻠﺐ‬
‫ﻣﺴﺘﻮﻳﺎت أﻋﻠﻰ ﻣﻦ اﻟﺠﻠﻮﻛﻮز ﻓﻲ اﻟﺪم ﻟﺒﺪء إﻓﺮاز اﻷﻧﺴﻮﻟﻴﻦ‪ .‬ﻳُ ﺒﺎع ﻛﻞ ﻣﻦ اﻟﻤﻴﺠﻠﻴﺘﻴﻨﻴﺪات‪ ،‬اﻟﻤﻌﺮوف ﺑﺎﺳﻢ ﻧﺎﺗﻴﻐﻠﻴﻨﻴﺪ‬
‫ورﻳﺒﺎﻏﻠﻴﻨﻴﺪ‪ ،‬ﻓﻲ ﺗﺮﻛﻴﺒﺎت ﻣﻘﺘﺮﻧﺔ ﺑﺎﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‪ .‬ﺗﺒﺎع ﺗﺮﻛﻴﺒﺔ رﻳﺒﺎﻏﻠﻴﻨﻴﺪ‪ /‬ﻣﻴﺘﻔﻮرﻣﻴﻦ ﻋﻠﻰ أﻧﻬﺎ ﺑﺮاﻧﺪﻳﻤﺖ‪ ،‬أو ﻛﻤﻜﺎﻓﺊ ﻋﺎم ﻟﻬﺎ‪.‬‬

‫ﻋﻼج ﺛﻼﺛﻲ‬
‫ﻋ…‬
‫ﻣﺰﻳﺞ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻣﻊ داﺑﺎﺟﻠﻴﻔﻠﻮزﻳﻦ وﺳﺎﻛﺴﺎﺟﻠﻴﺒﺘﻴﻦ ﻣﺘﺎح ﻓﻲ اﻟﻮﻻﻳﺎت اﻟﻤﺘﺤﺪة ﺑﺎﺳﻢ ﻛﻴﻮﺗﻴﺮﻧﻤﻴﺖ اﻛﺲ ار )‪Qternmet‬‬
‫]‪[177‬‬ ‫‪.(XR‬‬

‫ﻣﺰﻳﺞ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻣﻊ ﺑﻴﻮﻏﻠﻴﺘﺎزون وﻏﻠﻴﺒﻴﻨﻜﻼﻣﻴﺪ ]‪ [178‬ﻣﺘﻮﻓﺮ ﻓﻲ اﻟﻬﻨﺪ ﻣﺜﻞ ‪ Accuglim-MP‬و‪Adglim MP‬‬

‫]‪[146‬‬
‫و‪ Alnamet-GP‬واﻟﻔﻠﺒﻴﻦ ﺑﺎﺳﻢ ‪.Tri-Senza‬‬

‫]‪[179‬‬
‫ﻣﺰﻳﺞ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻣﻊ ﺑﻴﻮﺟﻠﻴﺘﺎزون وﺣﻤﺾ ﻟﻴﺒﻮﻳﻚ ﻣﺘﺎح ﻓﻲ ﺗﺮﻛﻴﺎ ﺑﺎﺳﻢ ﺑﻴﻮﻧﺎل‪.‬‬
 ‫اﻟﺸﻮاﺋﺐ‬
‫ﻋ…‬
‫ ﻃﺎﻟﻊ ً‬
‫أﻳﻀﺎ‪ :‬راﻧﻴﺘﻴﺪﻳﻦ‬

‫أﻋﻠﻨﺖ إدارة اﻟﻐﺬاء واﻟﺪواء اﻷﻣﺮﻳﻜﻴﺔ )‪ (FDA‬ﻓﻲ دﻳﺴﻤﺒﺮ ‪ 2019‬أﻧﻬﺎ ﻋﻠﻤﺖ أن ﺑﻌﺾ أدوﻳﺔ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ اﻟﻤﺼﻨﻌﺔ ﺧﺎرج‬

‫اﻟﻮﻻﻳﺎت اﻟﻤﺘﺤﺪة ﻗﺪ ﺗﺤﺘﻮي ﻋﻠﻰ ﺷﻮاﺋﺐ ﻧﻴﺘﺮوﺳﺎﻣﻴﻦ ﺗﺴﻤﻰ ﺛﻨﺎﺋﻲ ﻣﻴﺜﻴﻞ ﻧﺘﺮوزاﻣﻴﻦ )ﺑﺎﻹﻧﺠﻠﻴﺰﻳﺔ‪N- :‬‬
‫( واﻟﻤﺨﺘﺼﺮة "‪ ،"NDMA‬اﻟﻤﺼﻨﻔﺔ ﻋﻠﻰ أﻧﻬﺎ ﻣﺎدة ﻣﺴﺮﻃﻨﺔ‬ ‫‪Nitrosodimethylamine‬‬
‫ﻣﺤﺘﻤﻠﺔ ﻟﻺﻧﺴﺎن ﻋﻨﺪ ﻣﺴﺘﻮﻳﺎت ﻣﻨﺨﻔﻀﺔ‪ [180] .‬أﻋﻠﻨﺖ وزارة اﻟﺼﺤﺔ اﻟﻜﻨﺪﻳﺔ أﻧﻬﺎ ﺗﻘﻴﻢ ﻣﺴﺘﻮﻳﺎت ﻧﺘﺮوزو ﺛﻨﺎﺋﻲ ﻣﺜﻴﻞ أﻻﻧﻴﻦ‬
‫ﻓﻲ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‪.‬‬

‫ﻓﻲ ﻓﺒﺮاﻳﺮ ‪ ،2020‬وﺟﺪت إدارة اﻟﻐﺬاء واﻟﺪواء ﻣﺴﺘﻮﻳﺎت ﻧﺘﺮوزو ﺛﻨﺎﺋﻲ ﻣﺜﻴﻞ أﻻﻧﻴﻦ ﻓﻲ ﺑﻌﺾ ﻋﻴﻨﺎت اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ اﻟﻤﺨﺘﺒﺮة‬
‫اﻟﺘﻲ ﻟﻢ ﺗﺘﺠﺎوز اﻟﻤﺪﺧﻮل اﻟﻴﻮﻣﻲ اﻟﻤﻘﺒﻮل‪ .‬ﻓﻲ ﺷﺒﺎط )ﻓﺒﺮاﻳﺮ( ‪ ،2020‬أﻋﻠﻨﺖ وزارة اﻟﺼﺤﺔ اﻟﻜﻨﺪﻳﺔ ﻋﻦ ﺳﺤﺐ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‬
‫]‪[182] [181‬‬
‫اﻟﺬي ﻳﺤﺘﻮي ﻋﻠﻰ ﻣﺎدة أﺑﻮﺗﻴﻜﺲ‪.‬‬

‫ﻓﻲ ‪ 29‬ﻣﺎﻳﻮ ‪ ،2020‬ﻃﻠﺒﺖ إدارة اﻟﻐﺬاء واﻟﺪواء ﻣﻦ ﺧﻤﺲ ﺷﺮﻛﺎت أن ﺗﺴﺘﺪﻋﻲ ﻃﻮاﻋﻴﺔ ﻣﻨﺘﺠﺎت اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ذات اﻹﻃﻼق‬
‫اﻟﻤﺴﺘﻤﺮ‪ [188] [187] [186] [185] [184] [183] .‬ﻟﻢ ﻳﺘﻢ اﻟﻜﺸﻒ ﻋﻦ أﺳﻤﺎء اﻟﺸﺮﻛﺎت اﻟﺨﻤﺲ‪ ،‬اﻟﺼﻴﺪﻟﻴﺔ اﻟﺘﻲ أﺑﻠﻐﺖ إدارة اﻟﻐﺬاء‬
‫]‪[189‬‬
‫واﻟﺪواء ﻷول ﻣﺮة ﺑﻬﺬا اﻟﻤﻠﻮث ﻓﻲ اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﻋﺒﺮ ﻋﺮﻳﻀﺔ اﻟﻤﻮاﻃﻦ‪.‬‬

‫ﻓﻲ ﻳﻮﻧﻴﻮ ‪ ،2020‬ﻧﺸﺮت إدارة اﻟﻐﺬاء واﻟﺪواء اﻷﻣﺮﻳﻜﻴﺔ ﻧﺘﺎﺋﺠﻬﺎ اﻟﻤﻌﻤﻠﻴﺔ اﻟﺘﻲ ﺗﻈﻬﺮ ﻛﻤﻴﺎت ﻧﺘﺮوزو ﺛﻨﺎﺋﻲ ﻣﺜﻴﻞ أﻻﻧﻴﻦ ﻓﻲ‬
‫ﻣﻨﺘﺠﺎت اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ اﻟﺘﻲ اﺧﺘﺒﺮﺗﻬﺎ‪ [190] .‬ﻟﻘﺪ وﺟﺪت ﻧﺘﺮوزو ﺛﻨﺎﺋﻲ ﻣﺜﻴﻞ أﻻﻧﻴﻦ ﻓﻲ ﻋﺪد ﻣﻌﻴﻦ ﻣﻦ ﻣﻴﺘﻔﻮرﻣﻴﻦ ‪ ،ER‬وﺗﻮﺻﻲ‬
‫اﻟﺸﺮﻛﺎت ﺑﺴﺤﺐ اﻟﻜﺜﻴﺮ ﺑﻤﺴﺘﻮﻳﺎت ﻧﺘﺮوزو ﺛﻨﺎﺋﻲ ﻣﺜﻴﻞ أﻻﻧﻴﻦ أﻋﻠﻰ ﻣﻦ ﺣﺪ اﻻﺳﺘﻬﻼك اﻟﻤﻘﺒﻮل اﻟﺒﺎﻟﻎ ‪ 96‬ﻧﺎﻧﻮﺟﺮام ﻓﻲ اﻟﻴﻮم‪.‬‬
‫]‪ [190‬ﺗﺘﻌﺎون إدارة اﻟﻐﺬاء واﻟﺪواء ً‬
‫أﻳﻀﺎ ﻣﻊ اﻟﻤﻨﻈﻤﻴﻦ اﻟﺪوﻟﻴﻴﻦ ﻟﻤﺸﺎرﻛﺔ ﻧﺘﺎﺋﺞ اﺧﺘﺒﺎر اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ‪.‬‬

‫ﻓﻲ ﻳﻮﻟﻴﻮ ‪ ،2020‬اﻧﺴﺤﺒﺖ ﻟﻮﺑﻴﻦ اﻟﺼﻴﺪﻟﺔ ﻋﻦ اﻟﻜﺜﻴﺮ )دﻓﻌﺎت( اﻟﻤﻴﺘﻔﻮرﻣﻴﻦ ﺑﻌﺪ اﻛﺘﺸﺎف ﻣﺴﺘﻮﻳﺎت ﻋﺎﻟﻴﺔ ﻏﻴﺮ ﻣﻘﺒﻮﻟﺔ ﻣﻦ‬
‫]‪[191‬‬
‫ﻧﺘﺮوزو ﺛﻨﺎﺋﻲ ﻣﺜﻴﻞ أﻻﻧﻴﻦ ﻓﻲ اﻟﻌﻴﻨﺎت اﻟﺘﻲ ﻓﺤﺼﺖ‪.‬‬

‫]‪[192‬‬
‫ﻓﻲ أﻏﺴﻄﺲ ‪ ،2020‬ﻗﺎﻣﺖ ﺷﺮﻛﺔ ﺑﺎﻳﺸﻮر ﻟﻸدوﻳﺔ ﺑﺴﺤﺐ ﻗﻄﻌﺘﻴﻦ ﻣﻦ اﻷﺟﻬﺰة اﻟﻠﻮﺣﻴﺔ‪.‬‬

‫اﻟﻤﺮاﺟﻊ‬

‫‪Metformin Hydrochloride" (https://web.archive.org/web/20161224162245/https://www.drugs.com/mon" .1‬‬

‫‪ . ograph/metformin-hydrochloride.html). The American Society of Health-System Pharmacists‬ﻣﺆرﺷﻒ‬
‫ﻓﻲ ‪ 24‬دﻳﺴﻤﺒﺮ ‪ .2016‬اﻃﻠﻊ‬ ‫ﻣﻦ اﻷﺻﻞ )‪(https://www.drugs.com/monograph/metformin-hydrochloride.html‬‬
‫ﻋﻠﻴﻪ ﺑﺘﺎرﻳﺦ ‪ 02‬ﻳﻨﺎﻳﺮ ‪.2017‬‬
Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A" .2
Systematic Review and Meta-analysis". Annals of Internal Medicine. 164 (11): 740–51. June 2016.
doi: 10.7326/M15-2650 (https://doi.org/10.7326%2FM15-2650). PMID 27088241 (https://pubmed.ncbi.
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Clinical Obesity (https://web.archive.org/web/20170908185309/https://books.google.com/books?id=qG .3

978-0-470- ISBN .262 ‫ ﺻﻔﺤﺔ‬.2nd). Oxford: John Wiley & Sons. 2008 ‫)اﻟﻄﺒﻌﺔ‬ (VnItPoPCYC&pg=PA262
‫ ﺳﺒﺘﻤﺒﺮ‬08 ‫ﻓﻲ‬ (https://books.google.com/books?id=qGVnItPoPCYC&pg=PA262) ‫ ﻣﺆرﺷﻒ ﻣﻦ اﻷﺻﻞ‬.98708-7
.2017

Type 2 diabetes and metformin. First choice for monotherapy: weak evidence of efficacy but well-known" .4
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ety/recalls-market-withdrawals-safety-alerts/teva-pharmaceuticals-usa-inc-initiates-voluntary-nationwide-
.2020 ‫ ﻳﻮﻧﻴﻮ‬05 ‫ اﻃﻠﻊ ﻋﻠﻴﻪ ﺑﺘﺎرﻳﺦ‬.2021 ‫ ﻳﻨﺎﻳﺮ‬21 ‫ﻓﻲ‬ (recall-metformin-hydrochloride-extended
 Marksans Pharma Limited Issues Voluntary Nationwide Recall of Metformin Hydrochloride Extended-" .1
Release Tablets, USP 500mg, Due to the Detection of N-Nitrosodimethylamine (NDMA)" (https://web.arch
ive.org/web/20210123205407/https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/mar
ksans-pharma-limited-issues-voluntary-nationwide-recall-metformin-hydrochloride-extended-release).
https://www.fda.gov/safety/recalls-market-with) ‫ ﻣﺆرﺷﻒ ﻣﻦ اﻷﺻﻞ‬.FDA). 2 June 2020) ‫ إدارة اﻟﻐﺬاء واﻟﺪواء‬.U.S
drawals-safety-alerts/marksans-pharma-limited-issues-voluntary-nationwide-recall-metformin-hydrochlori
.2020 ‫ ﻳﻮﻧﻴﻮ‬05 ‫ اﻃﻠﻊ ﻋﻠﻴﻪ ﺑﺘﺎرﻳﺦ‬.2021 ‫ ﻳﻨﺎﻳﺮ‬23 ‫ﻓﻲ‬ (de-extended-release

Re: Docket No. FDA-2020-P-0978" (https://web.archive.org/web/20210208080851/https://downloads.re" .1 9

FDA). 28 May) ‫ إدارة اﻟﻐﺬاء واﻟﺪواء‬. gulations.gov/FDA-2020-P-0978-0007/attachment_1.pdf) (PDF). U.S
https://downloads.regulations.gov/FDA-2020-P-0978-0007/attachment_1.pdf)) ‫ ﻣﺆرﺷﻒ ﻣﻦ اﻷﺻﻞ‬.2020
.2020 ‫ ﻳﻮﻧﻴﻮ‬02 ‫ اﻃﻠﻊ ﻋﻠﻴﻪ ﺑﺘﺎرﻳﺦ‬.2021 ‫ ﻓﺒﺮاﻳﺮ‬08 ‫(( ﻓﻲ‬PDF

Laboratory Tests - Metformin" (https://web.archive.org/web/20210422093108/https://www.fda.gov/dru" .190

.FDA). 5 June 2020) ‫ إدارة اﻟﻐﺬاء واﻟﺪواء‬. gs/drug-safety-and-availability/laboratory-tests-metformin). U.S
‫ﻓﻲ‬ (https://www.fda.gov/drugs/drug-safety-and-availability/laboratory-tests-metformin) ‫ﻣﺆرﺷﻒ ﻣﻦ اﻷﺻﻞ‬
.2020 ‫ ﻳﻮﻧﻴﻮ‬05 ‫ اﻃﻠﻊ ﻋﻠﻴﻪ ﺑﺘﺎرﻳﺦ‬.2021 ‫ أﺑﺮﻳﻞ‬22

Lupin Pharmaceuticals Inc. "Lupin Pharmaceuticals, Inc. Issues Voluntarily Nationwide Recall of .191
Metformin Hydrochloride Extended-Release Tablets, 500mg and 1000mg Due to the Detection of N-
Nitrosodimethylamine (NDMA) Impurity" (https://web.archive.org/web/20210609205427/https://www.pr
newswire.com/news-releases/lupin-pharmaceuticals-inc-issues-voluntarily-nationwide-recall-of-metformi
n-hydrochloride-extended-release-tablets-500mg-and-1000mg-due-to-the-detection-of--n-nitrosodimethyla
https://w) ‫ ﻣﺆرﺷﻒ ﻣﻦ اﻷﺻﻞ‬.(‫)ﺑﺎﻟﻠﻐﺔ اﻹﻧﺠﻠﻴﺰﻳﺔ‬ mine-ndma-impurity-301089754.html). www.prnewswire.com
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.2020 ‫ ﻳﻮﻟﻴﻮ‬09 ‫ اﻃﻠﻊ ﻋﻠﻴﻪ ﺑﺘﺎرﻳﺦ‬.2021 ‫ ﻳﻮﻧﻴﻮ‬9 ‫ﻓﻲ‬ (ethylamine-ndma-impurity-301089754.html

Bayshore Pharmaceuticals, LLC Issues Voluntary Nationwide Recall of Metformin Hydrochloride" .192
Extended-Release Tablets USP, 500 mg and 750 mg Due to the Detection of N-Nitrosodimethylamine
(NDMA) Impurity" (https://web.archive.org/web/20201219234633/https://www.fda.gov/safety/recalls-m
arket-withdrawals-safety-alerts/bayshore-pharmaceuticals-llc-issues-voluntary-nationwide-recall-metform
https://www.f) ‫ ﻣﺆرﺷﻒ ﻣﻦ اﻷﺻﻞ‬.FDA). 19 August 2020) ‫ إدارة اﻟﻐﺬاء واﻟﺪواء‬. in-hydrochloride-extended). U.S
da.gov/safety/recalls-market-withdrawals-safety-alerts/bayshore-pharmaceuticals-llc-issues-voluntary-na
.2020 ‫ أﻏﺴﻄﺲ‬25 ‫ اﻃﻠﻊ ﻋﻠﻴﻪ ﺑﺘﺎرﻳﺦ‬.2020 ‫ دﻳﺴﻤﺒﺮ‬19 ‫ﻓﻲ‬ (tionwide-recall-metformin-hydrochloride-extended

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