Talk:Abnormal Development - Thalidomide
Introduction
Thalidomide is a drug that was introduced on to the market on October 1, 1957 in West Germany. Thalidomide soon became a drug prescribed to pregnant women to combat symptoms associated with morning sickness.
When taken during the first trimester of pregnancy, Thalidomide prevented the proper growth of the foetus resulting in horrific birth defects in thousands of children around the world.
It was the linking of newborn abnormalities with the taking of thalidomide by an Australian clinician, William McBride, that identified it as a teratogenic agent causing a "thalidomide embryopathy".
Children were born with limb and other defects, mainly in first world countries, in the late 1950's and early 1960's and became known as "Thalidomide babies". (More? [../Notes/skmus2.htm#LIMB%20REDUCTION Musculoskeletal Abnormalities - Limb Reduction])
Not all species embryos are affected by the drug in the same way, with human and rabbit being most susceptible to the teratogenic effects. In addition, the effect on human development is also dependent upon the time and dose of the drug exposure, the "critical periods".
More recent research has shown a clinical revival for thalidomide in its use in non-pregnant women during cancer chemotherapy.
Page Links: [#Intro Introduction] | [#Recent Some Recent Findings] | [#chemotherapy Chemotherapy] | [#References References] | [#Books Books] | [#WWWLinks WWW Links] | [#Glossary Glossary]
Some Recent Findings
Knobloch J, Rüther U. Shedding light on an old mystery: Thalidomide suppresses survival pathways to induce limb defects. Cell Cycle. 2008 Feb 14;7(9)
"Many hypotheses have been proposed to explain the molecular mechanism of thalidomide teratogenicity, in particular regarding to limb defects. Most experimental evidence in vivo has been provided for a model that suggests the generation of oxidative stress by thalidomide with subsequent down-regulation of Wnt and Akt survival pathways. ...We extend this model by presenting new data demonstrating an involvement of the transcription factors Tbx5 and Sall4 in thalidomide-induced molecular pathology."
Benegbi M. 45 years later...where do we stand? Can J Clin Pharmacol. 2007 Winter;14(1):e37-9.
Li PK, Pandit B, Sackett DL, Hu Z, Zink J, Zhi J, Freeman D, Robey RW, Werbovetz K, Lewis A, Li C. A thalidomide analogue with in vitro antiproliferative, antimitotic, and microtubule-stabilizing activities. Mol Cancer Ther. 2006 Feb;5(2):450-6.
Chemotherapy
References
Reviews
McBride WG. Thalidomide embryopathy. Teratology. 1977 Aug;16(1):79-82.
Saunders EJ, Saunders JA. Drug therapy in pregnancy: the lessons of diethylstilbestrol, thalidomide, and bendectin. Health Care Women Int. 1990;11(4):423-32.
Stephens TD. Proposed mechanisms of action in thalidomide embryopathy. Teratology. 1988 Sep;38(3):229-39.
Newman CG The thalidomide syndrome: risks of exposure and spectrum of malformations. Clin Perinatol. 1986 Sep;13(3):555-73.
Fletcher I. Review of the treatment of thalidomide children with limb defeciency in Great Britain. Clin Orthop Relat Res. 1980 May;(148):18-25.
Articles
Benegbi M. 45 years later...where do we stand? Can J Clin Pharmacol. 2007 Winter;14(1):e37-9.
"The Thalidomide Victims Association of Canada (TVAC) was founded in 1988 and is the only organization in North America to work with and for Thalidomide victims. Our mission is to empower our members and to improve their quality of life through various programs and customized services. With the return of Thalidomide on the market, TVAC also took on the mandate of informing the public on the devastating effects of this medication and to promote awareness and caution when using any teratogenic products currently available".
McBride WG. Prescription drugs in the first trimester and congenital malformations. Aust N Z J Obstet Gynaecol. 1992 Nov;32(4):386.
Chuah B, Lim R, Boyer M, Ong AB, Wong SW, Kong HL, Millward M, Clarke S, Goh BC. Multi-centre phase II trial of Thalidomide in the treatment of unresectable hepatocellular carcinoma. Acta Oncol. 2007;46(2):234-8.
Li PK, Pandit B, Sackett DL, Hu Z, Zink J, Zhi J, Freeman D, Robey RW, Werbovetz K, Lewis A, Li C. A thalidomide analogue with in vitro antiproliferative, antimitotic, and microtubule-stabilizing activities. Mol Cancer Ther. 2006 Feb;5(2):450-6.
Search Pubmed Now: [TITL&doptcmdl=DocSum Thalidomide[TITL]] (2007: 2,672 Articles, 253 Reviews) | Drug use in pregnancy
Books on Thalidomide
A selection of recent general public information books on Thalidomide, available from various internet commercial suppliers (search using the book title). Please note that this listing does not reflect an endorsement of the book or its content and is provided for educational purposes only.
Thalidomide Kid (Paperback) by Kate, Rigby (Author)
Thalidomide - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References (Paperback) by ICON Health Publications (Author)
Internet supplier link: Amazon
WWW Links
- Medline Plus - Thalidomide
- USA FDA - Thalidomide
- Thalidomide Victims Association of Canada
- Thalidomide Isomerism and Optical Isomerism
- United Nations International Drug Control Programme
- Australian Drug Foundation (ADF)
- Centre for Education and Information on Drugs and Alcohol (CEIDA) (Australia)
- Child Health and Safety (Australia)
- NIDA (USA)- Consequences of Prenatal Drug Exposure
- Australian Medicines Handbook (no electronic version yet)
