Thalidomide: Difference between revisions

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'''Thalidomide''' is a [[biologic response modifier]] with an increasing number of applications in severe inflammatory, immune, or dermatologic diseases. It is anti-inflammatory, anti-angiogenic, and immulomodulatory. Originally introduced as a sedative in the 1950s, it causes extreme fetal malformations or fetal death, and was unavailable for many years. It was reintroduced for the narrow indication of preventing and treating severe skin reactions in [[leprosy]], and for [[multiple myeloma]].
'''Thalidomide''' is a [[biologic response modifier]] with an increasing number of applications in severe inflammatory, immune, or dermatologic diseases. It is anti-inflammatory, anti-angiogenic, and immulomodulatory. Originally introduced as a sedative in the 1950s, it causes extreme fetal malformations or fetal death, and was unavailable for many years. A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects.<ref>{{MeSH}}</ref>
 
----
'''Thalidomide is absolutely  contraindicated in pregnancy. Female patients who receive it <u>must</u> use two forms of contraception.'''
'''Thalidomide is absolutely  contraindicated in pregnancy. Female patients who receive it <u>must</u> use two forms of contraception.'''
----
==Indications==
==Indications==
Erythema Nodosum Leprosum, Multiple Myeloma, Prevention of Erythema Nodosum Leprosum
It was reintroduced for the narrow indication of preventing and treating severe skin reactions in [[leprosy]], and for [[multiple myeloma]].  Approved usages as an [[orphan drug]] extended to [[AIDS wasting syndrome]], prevention and treatment of severe recurrent aphthous stomatitis in severely, terminally immunocompromised patients†; prevention and treatment of [[graft-versus-host disease]] in patients receiving bone marrow transplantation; treatment of clinical manifestations of both tuberculous and nontuberculous mycobacterial infection; treatment of [[Crohn’s disease]]; and treatment of primary brain tumors.


Thalidomide also has been designated an orphan drug by FDA for treatment of wasting syndrome associated with human immunodeficiency virus (HIV) infection†; prevention and treatment of severe recurrent aphthous stomatitis in severely, terminally immunocompromised patients†; prevention and treatment of graft-versus-host disease in patients receiving bone marrow transplantation†; treatment of clinical manifestations of mycobacterial infection caused by Mycobacterium tuberculosis  and nontuberculous mycobacteria†; treatment of Crohn’s disease†; and treatment of primary brain tumors†. In addition, thalidomide has been used for the treatment of a variety of inflammatory and/or dermatologic disorders, treatment of various HIV-associated conditions, and treatment of various malignancies. Use of thalidomide may not limit disease progression and/or death.  
In addition, thalidomide has been used for the treatment of a variety of inflammatory and/or dermatologic disorders, treatment of various HIV-associated conditions, and treatment of various malignancies. <ref>{{citation
| url = http://www.medscape.com/druginfo/monograph?cid=med&drugid=16389&drugname=Thalidomide+Oral&monotype=monograph&secid=2
| title = Monograph: Thalidomide &mdash; Uses
| publisher = American Society of Health System Pharmacists/Medscape
}}</ref>
 
It has been used in [[Behcet's Syndrome]].<ref>{{citation
| title = Editorial: Behcet Disease and the Emergence of Thalidomide
| author =George E. Ehrlich
| journal = Ann Intern Med
| date = 15 March 1998  | volume = 128 | issue =6 | pages = 494-495
| url = http://www.annals.org/content/128/6/494.full
}}</ref>
==Pharmacology==  
==Pharmacology==  
While all of its mechanisms are not fully understood, its functions include:<ref>{{citation
While all of its mechanisms are not fully understood, its functions include:<ref>{{citation
  | http://www.medscape.com/druginfo/monograph?cid=med&drugid=16389&drugname=Thalidomide+Oral&monotype=monograph&secid=8
  | url = http://www.medscape.com/druginfo/monograph?cid=med&drugid=16389&drugname=Thalidomide+Oral&monotype=monograph&secid=8
  | title = Monograph: Thalidomide &mdash; Pharmacology
  | title = Monograph: Thalidomide &mdash; Pharmacology
  | publisher = American Society of Health System Pharmacists/Medscape
  | publisher = American Society of Health System Pharmacists/Medscape
Line 17: Line 30:
*Possible suppression of macrophage involvement of prostaglandin synthesis and modulation of [[interleukin-10]] and [[interleukin-12]] production by peripheral blood [[monocyte]]s.
*Possible suppression of macrophage involvement of prostaglandin synthesis and modulation of [[interleukin-10]] and [[interleukin-12]] production by peripheral blood [[monocyte]]s.


While its anti-inflammatory and immunomodulatory effects are complex, they appear different from those of other agents, including [[corticosteroid]]s, cyclosporin (e.g., [[cyclosporine]]) or macrolide (e.g., [[tacrolimus]]) immunosuppressants, [[pentoxifylline]], immunosuppressive purine analogs (e.g. [[azathioprine]]) and purine metabolism inhibitors (e.g., [[mycophenolic acid]]), and  nonsteroidal anti-inflammatory agents.  
While its anti-inflammatory and immunomodulatory effects are complex, they appear different from those of other agents, including [[corticosteroid]]s, cyclosporin (e.g., [[cyclosporine]]) or macrolide (e.g., [[tacrolimus]]) immunosuppressants, [[pentoxifylline]], immunosuppressive purine analogs (e.g. [[azathioprine]]) and purine metabolism inhibitors (e.g., [[mycophenolic acid]]), and  [[nonsteroidal anti-inflammatory drug]]s.  


It does not appear to interfere with antimicrobial defense mechanisms, lyphocyte proliferation, granuloma formation, and delayed hypersensitivity reactions.  
It does not appear to interfere with antimicrobial defense mechanisms, lyphocyte proliferation, granuloma formation, and delayed hypersensitivity reactions.  
==References==
==References==
{{reflist}}
{{reflist|2}}

Revision as of 22:16, 17 August 2010

Thalidomide is a biologic response modifier with an increasing number of applications in severe inflammatory, immune, or dermatologic diseases. It is anti-inflammatory, anti-angiogenic, and immulomodulatory. Originally introduced as a sedative in the 1950s, it causes extreme fetal malformations or fetal death, and was unavailable for many years. A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects.[1]


Thalidomide is absolutely contraindicated in pregnancy. Female patients who receive it must use two forms of contraception.


Indications

It was reintroduced for the narrow indication of preventing and treating severe skin reactions in leprosy, and for multiple myeloma. Approved usages as an orphan drug extended to AIDS wasting syndrome, prevention and treatment of severe recurrent aphthous stomatitis in severely, terminally immunocompromised patients†; prevention and treatment of graft-versus-host disease in patients receiving bone marrow transplantation; treatment of clinical manifestations of both tuberculous and nontuberculous mycobacterial infection; treatment of Crohn’s disease; and treatment of primary brain tumors.

In addition, thalidomide has been used for the treatment of a variety of inflammatory and/or dermatologic disorders, treatment of various HIV-associated conditions, and treatment of various malignancies. [2]

It has been used in Behcet's Syndrome.[3]

Pharmacology

While all of its mechanisms are not fully understood, its functions include:[4]

While its anti-inflammatory and immunomodulatory effects are complex, they appear different from those of other agents, including corticosteroids, cyclosporin (e.g., cyclosporine) or macrolide (e.g., tacrolimus) immunosuppressants, pentoxifylline, immunosuppressive purine analogs (e.g. azathioprine) and purine metabolism inhibitors (e.g., mycophenolic acid), and nonsteroidal anti-inflammatory drugs.

It does not appear to interfere with antimicrobial defense mechanisms, lyphocyte proliferation, granuloma formation, and delayed hypersensitivity reactions.

References

  1. Anonymous (2024), Thalidomide (English). Medical Subject Headings. U.S. National Library of Medicine.
  2. Monograph: Thalidomide — Uses, American Society of Health System Pharmacists/Medscape
  3. George E. Ehrlich (15 March 1998), "Editorial: Behcet Disease and the Emergence of Thalidomide", Ann Intern Med 128 (6): 494-495
  4. Monograph: Thalidomide — Pharmacology, American Society of Health System Pharmacists/Medscape