Research Paper On Thalidomide

Thalidomide was originally invented in the 1950s by the Swiss pharmaceutical company. It was then initially released by the German company Chemie Grunenthalas in 1957 and was advertised to be one of the safest sedative drugs which is non-addictive (Kim & Scialli, 2011). Additionally, due to its effect in helping pregnant women to reduce the symptoms of morning sickness, thalidomide became widespread around the world; it was sold in more than 40 countries and was known as different names; for example, Distaval in Australia or Contergan in Germany (Vargesson, 2009). In spite of its popularity, thalidomide was banned in most countries after few years due to its tragical impact in neonates. In 1961, thalidomide was soon confirmed by two independent
clinicians, William McBride - the Australian obstetrician, and Widukind Lenz - the German pediatrician , to be a reason for a huge problem, which was the birth defects in babies, whose mothers had used thalidomide for symptomatic treatment for morning sickness. Nearly 10,000 cases of babies, who were born with severe malformation, was recorded around the world (Smithells & Newman, 1992).

There are malformations of various organs in new-born babies which were recorded around the world. Limb deformities which include four limb phocomelia, upper and lower limb malformations and other forelimb defects, are noted with 79% to 89% of cases with the congenital disorder (Smithells and Newman, 1992). Other significant organ deformities including ear deformities (for example, anotia or choanal atresia), eye defects (for example, microphthalmia or coloboma), genitals, kidneys, brain, and gut, which account for 11% to 21% (Lenz and Knapp, 1962). Other common anomalies which are recorded are heart defects, cryptorchism, abnormal development of larynx and trachea, gastrointestinal deformities (for example, intestinal atresia or congenital agenesis of the gallbladder), and dysfunction of the central nervous system (Ito, Ando, Suzuki, Ogura, Hotta, Imamura, Yamaguchi, and Handa, 2010). Children who were born nowadays with similar malformations as their parents, who have defects due to thalidomide, have been raising a suspicion that thalidomide can affect the frequency or particularity of deformities of the next generation of parents with thalidomide embryopathy; however, there is no evidence which has been found to prove that (Stromland, Philipson, & Gronlund, 2002).

The number of days pregnant the mother was could affect the severity and location of the defects on the babies. In his study, Vargersson (2009) points out that thalidomide could have caused central brain damage if it had been taken on the twentieth day of pregnancy, or eye deformities if it had been used on the twenty-first day of pregnancy, or ear and face malformations if the mother had used it on the twenty-second day of their gestation. The window of thalidomide exposure for upper extremity malformations is days 24–32 after fertilization while the sensitive period during pregnancy for thalidomide effects on lower limb malformations is days 27–34 (Hanseng, Gong, Philbert and Harris, 2002). If it is taken after 6-week gestation, thalidomide will not damage the fetus seriously (Smithells and Newman, 1992). Additionally, thalidomide was proved to give rise to the number of the mothers who had miscarriages in their gestations (Stromland, Philipson, & Gronlund, 2002).

The thalidomide mechanism of action which leads to the birth defects still remains unclear in spite of many hypotheses.
Hanse, Gong, Philbert, and Harris (2002) report that thalidomide can damage the cells and lead to teratogenicity by increasing the amount of oxygen radicals produced and inducing oxidative stress. On the other side, in their study, Stephens, Bunde and Fillmore (2000) demonstrate that thalidomide tends to inhibit angiogenesis by reducing the production of IGF-1 and FGF-2. IGF-1 and FGF-2 are the factors that play a role in stimulating the first step of alpha 5- and beta 3-integrin subunit genes expression, which leads to the stimulation of the formation of new blood vessels. Another study of Ito, Ando, Suzuki, Ogura, Hotta, Imamura, Yamaguchi, and Handa (2010) provides evidence to support that CRBN - a thalidomide-binding protein – can damage Cullin-4A and DNA binding protein 1, which are the essential factors for the limb
development.

Although it resulted in one of the most serious medical tragedy in the history, which is birth defects, thalidomide is used successfully now to treat multiple myeloma and leprosy.
In his study, Stroud (2005) suggests that thalidomide has a positive impact in treating cancer due to its antiangiogenic effect and reducing the results of cachexia including weight loss, a loss of appetite or progressive muscle atrophy. Its positive activity in anti-inflammation is also used in treating severe ENL (Erythema nodosum leprosum). However, Prommer, Twycross, Myhalyo, & Wilcock (2011) point out that using thalidomide can lead to a variety of adverse effects. For example, almost patients may experience constipation, weakness, dizziness, fatigue and mild decrease in bowel motility (Prommer, Twycross, Myhalyo, & Wilcock, 2011); other side effects of that drug can be arrhythmia, hypotension, edema, sinus bradycardia, orthostatic hypotension, severe skin reactions, tumor flare, increased lymphadenopathy, enlargement of the spleen, seizures, altered temperature sensitivity, irregular menstrual cycles, hypothyroidism or an increase in HIV viral
load.