Therapeutic Effects of Thalidomide - Case Study Example

Biology Genetics Thalidomide Thalidomide is a drug with an important history. This drug was considered to have excellent therapeutic effects when it was brought into the market. It was introduced as a sleep inducing drug as well as a drug meant for relieving anxiety. It was also a very famous drug because it was considered not to have any toxic effects on the body and though for the purpose of cure the dosage amount of the drug was 100 mg but even if suicidal cases with reports of dosage ten times higher than this amount could be saved (Pratt et al 1990). This drug was introduced in the market in the mid 20th century in certain counties in Europe. The drug was highly promoted to an extent that it was even given the label of “safe hypnotic” and it was also prescribed for expecting mothers. Within a year links between the drug and a pathological condition of the nervous system were reported in which the patients became paralyzed and had loss of their sensory nervous functioning. But this association was highly denied by the pharmaceutical companies whose sales boosted to as high as one hundred thousand preparations in Western Germany per day (Dale et al 1999). Within ten years after the drug was in market, the occurrence of a congenital condition known as phocolemia increased to alarming levels. In this pathology the infants did not undergo proper development and presented with short limbs or there was no development of the limbs at all. In the ten years before the introduction of the drug, there were no cases of infants suffering from this condition. But after this duration within the period of 1959 to 1961 the number of reported of 154. In 1961, a child specialist found out the link between thalidomide and the pathology. It was then that a link between the drug and the condition started to become realized and it was understood that the disease acted as a teratogen . This drug was also related to other visceral defects in the infants who developed phocolemia (Pratt et al 1990). This drug was then banned from use in the year of 1961 and the effects brought about by the drug were labeled as a catastrophe of thalidomide because by the time it was withdrawn from the market, there were already ten thousand infants who were suffering from this crippling condition. The drug was responsible for the production of different effects depending upon the time of pregnancy when it was ingested and the time when the fetus came into contact with the toxic substance. If the intake was on the twenty first or twenty second day, it resulted in developmental defects in the ears and affected the cranial nerves of the nervous system as well. If the exposure period was between the twenty fourth and the twenty seventh day, it leads to the absence of the arms. Following two days reported defects of loss of limbs of arms and the legs. Between the thirtieth and thirty sixth days, deforming affects were seen in the hands and the infants suffered from anorectal stenosis. Thalidomide was labeled as a teratogenic drug because its affects were seen during the period of organ development roughly between the 17 and 60 days of pregnancy (Dale et al 1999). This drug was useful in a way that it led to an introduction of greater studies and extensive research before the introduction of drugs in the market. The issue for the particular recommendation of drugs during pregnancy was made more important. This drug led to the making of new laws by the Food and Drug Administration in the United States despite of the fact that thalidomide was not permitted to be sold in the country. This law which is known as the Kefauver-Harris Amendments to the Food, Drug and Cosmetic Act was implemented in 1962 and it asked for checking for the toxicity of drugs that had been made available since the year 1938 as well as the other drugs that were being introduced. Tests to be performed for the drugs were made clear as well as a pattern for the collection of side effects that were reported was established (Katzung 2004). The effects of thalidomide on the DNA and the cause for the congenital disorder phocolemia have many reasons. Thalidomide led to the malformations in babies because it was found that the drug had interactions with the DNA sequences. The drug possessed the capability of binding itself with the DNA. This mechanism was brought about by the facilitative structure of thalidomide which allowed to easy filling up of the spaces between the building blocks of the DNA molecule. Another important feature about the drug was that it possessed particular affinity for the nucleotide base guanine out of all the four nucleotide bases that the molecule actually possessed. It was with guanine that the drug actually interwove itself. Structural resemblance between the base guanine and the drug thalidomide has also been identified. As the drug possessed the ability of altering the highly specific structure of DNA, this could lead to disturbances towards the formation of the building blocks of the body particularly the proteins. The drug also possessed the ability to block the formation of new blood vessels which is a very important step during the period of organ development. This is because the fetus requires proper supply of substances which would promote its growth and alterations in the nutrient supply to particular areas could result in malformations. Since thalidomide inhibited the formation of blood vessels in the fetus, it resulted in incomplete growth of the limbs or it could also lead to the loss of the limbs because of restriction in its growth due to blockage in the blood supply. The extent of the result and the malformations and defects that were seen were mainly dependent upon the time of exposure to the drug (Stephens et al 2000). DNA is a molecule which codes for many proteins required by the body and it is via these proteins that the bodily mechanisms are properly integrated. DNA is responsible for the synthesis of one such protein which is known as integrin. This protein is synthesized in a similar manner as are all other proteins. integrins are considered to play an important part in the formation of blood vessels within the fetus. Thalidomide interfered with the DNA molecule and it has been found that it leads to a reduction in the formation of integrins. This could be accounted for the loss of blood supply which led to thalidomide babies. This drug also led to deregulations in the synthesis of other important molecules which include insulin like growth factor and fibroblast growth factor. These alterations are also considered to be a cause for the improper development of blood vessels and hence the resultant effect of thalidomide was produced. (Stephens et al 2000) Despite of its many adverse effects thalidomide is a drug which has its own benefits and it has proved to be effective for curing many disease states. It can be used for the treatment of malignant conditions. The drug has been indicated in the treatment of malignant cancers of the cells of the kidney. It is also used in the treatment of Kaposi’s sarcoma which is the malignancy of the vessels. This condition is induced by the acquired immune deficiency syndrome. It is also very helpful for curing the weight reduction associated with human immunodeficiency virus. Lesions in the mouth and throat can also be treated by thalidomide (Mayo Clinic Staff 2009).It is also prescribed in glioblastoma multifome and myelomas (Adlard 2000). Thalidomide has proved to be effective in the treatment of erythema nodusum leprosum. This condition refers to the disease of skin that develops in leprosy. The effect of thalidomide on myelomas has led to the indication of this drug for the treatment of myelomas. Myeloma is the malignancy of the blood and the marrow of the bones. The drug can be used and is beneficial for the different levels of the myeloma. These stages include the new cases of myelomas, patients who suffer from this condition and have not been cured by other management procedures as well as patients who report of recurrence of myeloma. Thalidomide can be used as a measure of treatment for malignancies in a single form as well as in combination with other therapies (European Myeloma Platform 2007 and Mayo Clinic Staff 2009).Thalidomide plays a vital role in the treatment of inflammatory diseases which include the inflammation of the joints as well as Crohns disease. Inflammation is a process which leads to an increase in the tumor necrosis factor- alpha. The drug opposes this effect and lowers the level of this factor (Mayo Clinic Staff 2009). This drug is used to treat cancerous conditions but its mechanism of action is different from the chemotherapeutic agents. The chemotherapeutic agents work by the destruction of cells that are differentiating and hence they produce many side effects because they also have an impact upon the normal cells. This is the reason that treatments with these agents can lead to problems of the gastrointestinal tract and result in hair fall. But thalidomide works in a different manner as it performs its actions by alterations in the regulatory proteins which function to regulate specific mechanisms in the body (European Myeloma Platform 2007). Thalidomide is known to function by two different methods for the treatment of cancer. This drug is considered to have an effect on the immunity of a person by enhancing the immunity of a person against tumors and increasing its level of reactivity against these cancerous conditions. On the other hand a more important role played by the drug is somewhat similar to the effect it has during the period of the organ development in infants. When a malignant condition arises in the body, it leads to a rapid proliferation of the abnormal cells. These cells have a high differentiating power and they lead to the formation of new blood vessels for the provision of energy for this abnormal growth to continue. It is at this step of the cancers that thalidomide is considered to act. It has been found out that thalidomide functions to prevent the formation of the new vessels which causes cessation of the blood supply to these abnormally growing cells and hence putting a halt to their energy supply. This leads to prevent the cancer cells from growing. Other mechanisms for the functioning of the drug have also been explained which include target attacks to the proliferating cancerous cells as well as depriving them from their growth factors which produces the desired therapeutic indication for cancer treatment (European Myeloma Platform 2007). Though the indications of thalidomide have been clearly presented but still the drug does have many adverse effects which include pathologies of the peripheral nervous system, rashes on the skin and leads to decreased levels of the throid hormone. The drug also induces constipation. The drug can also lead to thrombosing arteries and patients who are mostly being treated with this drug are also administered other drugs in combination which can overcome these adverse effects (Katzung 2004). Thalidomide is a drug which presents with a history of crippling many lives but this disease can now be used to save people and treat their pathologies which could cripple their life. Hence there has been a great change from its initial role in leading to the birth of about 10,000 thalidomide babies to its latest role for treating cancerous conditions and saving the lives of many people. This drug is also considered to be important because it led to stricter implementation of rules for the checking of drugs before launching them in the market and the Federal Food and Drug Administration called for extensive research into the effects that a drug could possibly produce (Katzung 2004) References: Top of Form ADLARD JW. (2000). Thalidomide in the treatment of cancer. Anti-Cancer Drugs. 11, 787-91. Bottom of Form European Myeloma Platform (2007). Thalidomide. http://www.emp-myeloma.eu/Treatments/Thalidomide/tabid/69/Default.aspx Top of Form KATZUNG, B. G. (2004). Basic & clinical pharmacology. New York, Lange Medical Books/McGraw Hill. Mayo Clincial Staff. (2009).Thalidomide: Research advances in cancer and other conditions. http://www.mayoclinic.com/health/thalidomide/HQ01507 Top of Form PRATT, W. B., TAYLOR, P., & GOLDSTEIN, A. (1990).Principles of drug action: the basis of pharmacology. New York, Churchill Livingstone. Bottom of Form Top of Form RANG, H. P., DALE, M. M., & RITTER, J. M. (1999).Pharmacology. Edinburgh, Churchill Livingstone. Top of Form STEPHENS TD, BUNDE CJ, & FILLMORE BJ. (2000). Mechanism of action in thalidomide teratogenesis.Biochemical Pharmacology. 59, 1489-99. Bottom of Form Bottom of Form Bottom of Form Read More