Teratogenesis
It was previously believed that the mammalian embryo developed in the impervious uterus of the mother, protected from all extrinsic factors. However, after the thalidomide disaster of the 1960s, it became apparent and more accepted that the developing embryo could be highly vulnerable to certain environmental agents that have negligible or non-toxic effects to adult individuals.
It is estimated that 10% of all birth defects are caused by a prenatal exposure or teratogen.These exposures include, but are not limited to, medication or drug exposures, maternal infections and diseases, and environmental and occupational exposures. Teratogen-caused birth defects are potentially preventable.
Studies have shown that nearly 50% of pregnant women have been exposed to at least one medication during gestation.An additional study found that of 200 individuals referred for genetic counseling for a teratogenic exposure, 52% were exposed to more than one potential teratogen.
علم التشوهات الجنينيه بدا الاهتمام بيه بعد ملاحظه الاثار السلبيه التى حدثت نتيجه استخدام عقار يدعى thalidomide
THALIDOMIDE
It was the major couse of apperance of teratology science
It was used for morning sickness in pregnancy
as sedative-hypnotic and multiple myeloma medication
The drug is a potent teratogen in rabbits and primates including humans: severe birth defects may result if the drug is taken during pregnancy
Thalidomide was sold in a number of countries across the world from 1957 until 1961 when it was withdrawn from the market after being found to be a cause of birth defects in what has been called "the biggest medical tragedy of modern times".
It is not known exactly how many worldwide victims of the drug there have been, although estimates range from 10,000 to 20,000
Since then thalidomide has been found to be a valuable treatment for a number of medical conditions and it is being prescribed again in a number of countries, although its use remains controversial
The thalidomide tragedy led to much stricter testing being required for drugs and pesticides before they can be licensed
It couse
phochomelia ( shortening of limbs = sealed limbs occur mainly in arms > legs
amelia (no limbs)
internal malformation in eye & face
The mechanism of thalidomide's teratogenic action
Thalidomide intercalates (inserts itself) into DNA in G-C (guanine-cytosine) rich regions
Due to its glutarimide part, (S) thalidomide fits neatly into the major groove of DNA at purine sites . Such intercalation impacts upon the promoter regions of the genes controlling the development of limbs, ears, and eyes such as IGF-I and FGF-2. These normally activate the production of the cell surface attachment integrin αvβ3 with the resulting alphavbeta3 integrin dimer stimulating angiogenesis in developing limb buds. This then promotes the outgrowth of the bud (IGF-I and FGF-2 are also both known to stimulate angiogenesis). Therefore, by inhibiting the chain of events, thalidomide causes the truncation of limb development. In 2009 this theory received strong support, with research showing "conclusively that loss of newly formed blood vessels is the primary cause of thalidomide teratogenesis, and developing limbs are particularly susceptible because of their relatively immature, highly angiogenic vessel network."
Recently thalidomide may have an effect on immune system : the effect on blood vessels ( angiogenesis ) so thalidomide may be used in treatment of diabetes,HIV. Arthritis
Disadvantage
contraindicated in pregnancy
expensive
peripheral neuritis
التعليقات
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الصور دى توضح اهم اثر جانبى للثاليدوميد ....... الا وهو phochomelia = shortening of limbs
لذلك يعتبر category X بمعنى ممنوع نهائيا اثناء فتره الحمل
It was used for morning sickness in pregnancy
as sedative-hypnotic and multiple myeloma medication
الثاليدوميد كان بيستعمل بكتره ف الفتره اللى قبل طبعا ما يكتشفو اثاره الجانبيه وانو هو السبب ف الكارثه دى
كان من اكتر الادويه اللى كانت بتستعملها الحامل لعلاج الدوخه والدوار
ولما اكتشفو انو السبب ف التشوهات الجنينيه دى استخدام العقار ده تم سحبو من الاسواق وبدء الاهتمام بعلم teratology لدراسه كافه الادويه التانيه ودراسه اثارها ع الجنين ف فتره الحمل
يعتبر الكارثه الللى حصلت بسبب الثاليدوميد سبب ف نشاءه علم الteratology
بذكر أنو التاليدوميد استعمل أيضاً لعلاج الجذام العقيدي الإحمراري "الورمي الدرني" وحالياً في دراسة عليه لإستخدامه في علاج الساركوئيد الجلدي
Thalidomide was said to have been developed by German pharmaceutical company Grünenthal in Stolberg (Rhineland) near Aachen, although this claim has recently been challenged.
A report published by Dr Martin W Johnson, director of the Thalidomide Trust in the UK, detailed evidence that suggested the drug had been developed under the direction of a Nazi scientist in 1944, as an antidote to nerve gases such as sarin, ten years
before Grünenthal secured a patent in 1954.
Thalidomide was found to act as an effective tranquiliser and painkiller and was proclaimed as a "wonder drug" for insomnia, coughs, colds and headaches.
It was also found to be an effective antiemetic which had an inhibitory effect on morning sickness, and so thousands of pregnant women took the drug to relieve their symptoms.
ولهده الاسباب تم استخدامو ف فتره الحمل
At the time of the drug's development it was not thought likely that any drug could pass from the mother across the placental barrier and harm the developing foetus
pregnant mother taking Thalidomide
In the late 50s and early 60s, more than 10,000 children in 46 countries were born with deformities such as phocomelia, as a consequence of thalidomide use.
لكن العلماء اتكشفو سبب التشوهات الجنينيه تلك نتيجه تعاطى هذا العقار
The Australian obstetrician William McBride and the German pediatrician Widukind Lenz suspected a link between birth defects and the drug, and this was proved by Lenz in 1961.
McBride was later awarded a number of honours including a medal and prize money by the prestigious L'Institut de la Vie in Paris.
ونتيجه لذلك تم سحبو من الاسواق
In Germany approximately 2,500 thalidomide babies were born
كن هذا معناه انو الثاليدوميد ممنوع نهائا خلال فتره الحمل
ولا يمنع ذلك التحدث عن اهميته العلاجيه ف علاج امراض اخرى مهمه والتى منهااااا..........
Thalidomide also inhibits the growth of new blood vessels (angiogenesis), which may be useful in treating macular degeneration and other diseases. This effect helps AIDS patients with Kaposi's sarcoma, although there are better and cheaper drugs to treat the condition.
Thalidomide is also being investigated for treating symptoms of prostate cancer,
واشكركم كتييييييييييير ع مروركم والكلام الجميل ده
ثانكس دكتور حازم ..... ثانكس كتير دكتور اسبيرنت
اتمنى ديما نفيد ونستفيد